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1
TABLETSPRESENTED BY
ARANTHAJJOSEPHFIRST YEAR MPHARM
PHARMACEUTICS St josephs college of pharmacy cherthala
2 CONTENTS
Introduction Formulation Design Manufacturing
3 TABLETS
Tablets are solid preparations Consisting of one or more active ingredient Obtained by compressing uniform volumes of particles into various size and shape
4 THE ADVANTAGES OF THE TABLET bull They are unit dosage
bull Greatest dose precision and the least content variability
bull Cost is lowest of all oral dosage form
bull Lighter and compact
bull Easiest and cheapest to package
bull Easy to swallowing
bull Special release product is possible by enteric coating or delayed release product
5
bull odour and bitter taste can be masked by coating technique
bull Suitable for large scale production
bull Greatest chemical mechanical and microbial stability over all oral dosage form
bull Product identification is easy and cheapest
6DISADVANTAGES OF TABLET
bull Difficult to swallow in case of children and unconscious patients
bull Some drugs resist compression into dense compacts
bull Drugs with poor wetting slow dissolution properties is difficult to formulate
bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating
7DIFFERENT TYPES OF TABLETS
(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol
tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets
4 Delayed release tablet eg Enteric coated Bisacodyl
5 Sugar coated tablet eg Multivitamin tablet
6 Film coated tablet eg Metronidazole tablet
7 Chewable tablet eg Antacid tablet
8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol
tablet 3 Troches or lozenges 4 Dental cone
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
2 CONTENTS
Introduction Formulation Design Manufacturing
3 TABLETS
Tablets are solid preparations Consisting of one or more active ingredient Obtained by compressing uniform volumes of particles into various size and shape
4 THE ADVANTAGES OF THE TABLET bull They are unit dosage
bull Greatest dose precision and the least content variability
bull Cost is lowest of all oral dosage form
bull Lighter and compact
bull Easiest and cheapest to package
bull Easy to swallowing
bull Special release product is possible by enteric coating or delayed release product
5
bull odour and bitter taste can be masked by coating technique
bull Suitable for large scale production
bull Greatest chemical mechanical and microbial stability over all oral dosage form
bull Product identification is easy and cheapest
6DISADVANTAGES OF TABLET
bull Difficult to swallow in case of children and unconscious patients
bull Some drugs resist compression into dense compacts
bull Drugs with poor wetting slow dissolution properties is difficult to formulate
bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating
7DIFFERENT TYPES OF TABLETS
(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol
tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets
4 Delayed release tablet eg Enteric coated Bisacodyl
5 Sugar coated tablet eg Multivitamin tablet
6 Film coated tablet eg Metronidazole tablet
7 Chewable tablet eg Antacid tablet
8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol
tablet 3 Troches or lozenges 4 Dental cone
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
3 TABLETS
Tablets are solid preparations Consisting of one or more active ingredient Obtained by compressing uniform volumes of particles into various size and shape
4 THE ADVANTAGES OF THE TABLET bull They are unit dosage
bull Greatest dose precision and the least content variability
bull Cost is lowest of all oral dosage form
bull Lighter and compact
bull Easiest and cheapest to package
bull Easy to swallowing
bull Special release product is possible by enteric coating or delayed release product
5
bull odour and bitter taste can be masked by coating technique
bull Suitable for large scale production
bull Greatest chemical mechanical and microbial stability over all oral dosage form
bull Product identification is easy and cheapest
6DISADVANTAGES OF TABLET
bull Difficult to swallow in case of children and unconscious patients
bull Some drugs resist compression into dense compacts
bull Drugs with poor wetting slow dissolution properties is difficult to formulate
bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating
7DIFFERENT TYPES OF TABLETS
(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol
tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets
4 Delayed release tablet eg Enteric coated Bisacodyl
5 Sugar coated tablet eg Multivitamin tablet
6 Film coated tablet eg Metronidazole tablet
7 Chewable tablet eg Antacid tablet
8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol
tablet 3 Troches or lozenges 4 Dental cone
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
4 THE ADVANTAGES OF THE TABLET bull They are unit dosage
bull Greatest dose precision and the least content variability
bull Cost is lowest of all oral dosage form
bull Lighter and compact
bull Easiest and cheapest to package
bull Easy to swallowing
bull Special release product is possible by enteric coating or delayed release product
5
bull odour and bitter taste can be masked by coating technique
bull Suitable for large scale production
bull Greatest chemical mechanical and microbial stability over all oral dosage form
bull Product identification is easy and cheapest
6DISADVANTAGES OF TABLET
bull Difficult to swallow in case of children and unconscious patients
bull Some drugs resist compression into dense compacts
bull Drugs with poor wetting slow dissolution properties is difficult to formulate
bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating
7DIFFERENT TYPES OF TABLETS
(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol
tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets
4 Delayed release tablet eg Enteric coated Bisacodyl
5 Sugar coated tablet eg Multivitamin tablet
6 Film coated tablet eg Metronidazole tablet
7 Chewable tablet eg Antacid tablet
8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol
tablet 3 Troches or lozenges 4 Dental cone
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
5
bull odour and bitter taste can be masked by coating technique
bull Suitable for large scale production
bull Greatest chemical mechanical and microbial stability over all oral dosage form
bull Product identification is easy and cheapest
6DISADVANTAGES OF TABLET
bull Difficult to swallow in case of children and unconscious patients
bull Some drugs resist compression into dense compacts
bull Drugs with poor wetting slow dissolution properties is difficult to formulate
bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating
7DIFFERENT TYPES OF TABLETS
(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol
tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets
4 Delayed release tablet eg Enteric coated Bisacodyl
5 Sugar coated tablet eg Multivitamin tablet
6 Film coated tablet eg Metronidazole tablet
7 Chewable tablet eg Antacid tablet
8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol
tablet 3 Troches or lozenges 4 Dental cone
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
6DISADVANTAGES OF TABLET
bull Difficult to swallow in case of children and unconscious patients
bull Some drugs resist compression into dense compacts
bull Drugs with poor wetting slow dissolution properties is difficult to formulate
bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating
7DIFFERENT TYPES OF TABLETS
(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol
tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets
4 Delayed release tablet eg Enteric coated Bisacodyl
5 Sugar coated tablet eg Multivitamin tablet
6 Film coated tablet eg Metronidazole tablet
7 Chewable tablet eg Antacid tablet
8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol
tablet 3 Troches or lozenges 4 Dental cone
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
7DIFFERENT TYPES OF TABLETS
(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol
tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets
4 Delayed release tablet eg Enteric coated Bisacodyl
5 Sugar coated tablet eg Multivitamin tablet
6 Film coated tablet eg Metronidazole tablet
7 Chewable tablet eg Antacid tablet
8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol
tablet 3 Troches or lozenges 4 Dental cone
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol
tablet 3 Troches or lozenges 4 Dental cone
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet
(D) Tablets used to prepare solution
1 Effervescent tablet eg Dispirin tablet (Aspirin)
2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet
4 Tablet triturates eg Enzyme tablet (Digiplex)
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
10 TABLET GRANULATION
Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
1
11Powders intended for compression into tablets
must possess two essential properties
Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the
use of vibrators glidantPowder compressibilitybull The property of forming a stable intact
compact mass when pressure is applied is called powder compressibility
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
12ADVANTAGES OF GRANNULATION
bull To avoid powder segregation
bull To enhance the flow of powder
bull To produce uniform mixtures
bull To produce dust free formulations
bull To eliminate poor content uniformity
bull To improve compaction characteristics
of mix
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
13 Manufacturing of granules
Dry granulation method wet granulation method
Direct compression compression granulation Wet granulation
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
14Dry granulation
Compaction of powder
milling
screening
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
15 AdvantagesLess
equipments amp space
Eliminate need of binder
solution
Disadvantages
No uniform
color distributio
n
Process create
more dust
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
16Direct compression
Some Crystalline substances can compress directly Directly compressible diluent is an
Inert Compactable Maintain compression capacity even after adding disintegrates
and other ingredients Direct compression materials should posses
Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
17
DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant
LubricanttabletsCompression granulation
Weighing
Mixing [blender]
Slugging[tablet press roller compactorScreening sieve[20-25]
Mixing
Compression [tablet press]
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
18
Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
19 COMPRESSION GRANNULATION Dose of a drug is too high for its
compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by
means of tablet press or machine Milling and screening prior to fluid
compression
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
20 Roller compactor
On a large scale compression granulation can also be performed on a roller compactor
Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
21
It requires drugs or excipients with cohesive properties
Large particles must be used rarr (acceptable flowability and bulk density)
If the drug powder has low compatability it is difficult to form into tablets
Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose
LIMITATIONS OF DRY GRANULATION
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
22 WET GRANULATION
It involves massing of a mix of dry Primary powder particles using a Granulating fluid
The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol
The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
23
bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
24 Advantages of wet granulation
prevent segregation of the constituents of the powder blend
Improved cohesiveness and compressibility
To improve homogeneity Uniform distribution of contents and
colour The dissolution rate of hydrophobic
drugs may be improved by wet granulation method
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive
drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to
migration of dyes during drying stage
EquipmentsTraditionally dry mixing in wet granulation
process has been carried out usingSigma blade mixerHeavy-duty planetary mixer
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
26Granulation mechanism To form grannulesbond must be formed
between powder particles So they adhere Bond should be strong to prevent break
down 5 bonding mechanism
Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild
particles Formation of solid bridges after
solvent evaporation
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
27 Mechanism of granule formation
Divided into 3 Nucleation Transition Ball growth
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
28 GRANULATION EQUIPMENTS
Single pot granulator
High shear mixture granulator
Fluid bed granulator
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
29
Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment
eg Single Pot Processor One-Pot Processor
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
30 Single pot granulator
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
31 Rapid mixer granulator
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
33
Short processing time
Lesser amount of liquid binders required
Highly cohesive material can be granulated
Increase in temperature may cause chemical degradation of thermolabile material
Over wetting of granules can lead to
large size lumps formation
ADVANTAGES DISADVANTAGES
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
34 Fluid bed granulator
Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas
Granulating and drying can be completed in one
step inside the machine
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
35
-Homogeneous granules
---Gentle product handling
--Uniform spraying of all particles in the fluid bed
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
36 Advantages Reduces dust formation during
processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor
space requirements
DISADVANTAGES
The Fluid Bed cleaning is labor-intensive and time consuming
Difficulty of assuring reproducibility
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
37
Tablets Excipients
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
38
The common types of tabletrsquos excipients are described in the figure
Diluents
Binders $ adhesives
Disintegrants
Colours sweeten
ers $ flavors
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
39Diluent or filler Bulking agent
Increase size of the tablet Suitable for handling
Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
40 Requirements for a good diluent
Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
41 Disintegrants To ensure that the tablet when in contact
with a liquid breaks up into small fragments which promotes rapid drug dissolution
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
42Steps of the disintegration process
First The liquid wets the solid and penetrates the pores of the tablet
tablet breaks into smaller fragments
(aggregates of primary particles)
Second The aggregates will deaggregate into their primary powder particles
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
43 The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)
Mixed with the dry granules(EXTRA GRANULAR ADDITION)
Incorporated as both an intragranular and an extra granular portion
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl
cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
45 Binder Ensure that granules and tablets can be
formed with the required mechanical strength ( glue that holds powders together to form granules )
Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before
wet granulation As a dry powder in dry granulation (roller
compaction slugging)
2 Solution binder As a solution in wet granulation Binder can be added either dry with other
excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
47 Typical binder concentration is 2 ndash 10 by weight
Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol
egPovidone
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
48 LUBRICANT
Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction
Mechanisms of Action
1 Fluid lubrication 2 Boundary lubrication
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
49 1 Fluid lubrication A layer of fluid is located between the
moving surfaces separating them from each other amp thus reduces the friction
eg liquid paraffin
2 Boundary lubrication The sliding surfaces are separated by only a very
thin film of lubricant So the nature of the solid surfaces will therefore
affect friction
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
50
Disadvantages of lubricants 1 Lubricants tend to be hydrophobic
Under-lubricated blends tend to flow poorly and show compression sticking problems
Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to
granulation before tableting ( they reducing interparticulate friction)
Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
52 Antiadherent
Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face
Many lubricants such as magnesium stearate have also antiadherent properties
Also talc and starch can act as antiadherents
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
53 Sorbent
Are substances that are capable of sorbing some quantities of fluids in an apparently dry state
Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets
eg Microcrystalline cellulose amp silica
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
54 Flavor
Give the tablet a more pleasant taste or to mask an unpleasant one
Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat
They are often mixed with the granules as an alcohol solution
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
55 Colourent
It is added to tablets to aid identification and patient compliance
added during coating It can also be added prior to
compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
56Sweeteners
They are used in chewable tablet to exclude or limit the use of sugar in the tablets
Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace
saccharin Disadv Lack of stability in the
presence of moisture
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
57
Tablet compression
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
58 Tablet Compression Machine
Hopper for holding and feeding granules or powder to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granules within the dies
A feeding mechanism for moving granules from the hopper into the dies
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
59
Tablet machine or tablet press
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
60 The compression cycle for a singlepunch tablet machine
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
61Stages of Tablet Formation(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table into the die
(the die is closed at its lower end by the lower punch)
Tablet formation The upper punch descends enters the die the
powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper
punch leaves the powder
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
62 Tablet ejection
The lower punch rises until its tip reaches the level of the top of the die
The tablet is subsequently removed from the die and die table by a pushing device
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
63 Tablet presses
Single punch Rotary press High speed rotary press Multi layer rotary press
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
64 Single Punch press (Eccentric Press)
Bench-top models that make one tablet
At a time (single-station presses) Disadvantages production of
small batches of tablets
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
65 Rotary Press( Multi station Press) (10 000 tablets per minute)
Large scale production It consists of a number of dies and sets of
punches ( from 3 up to 60) The dies are mounted in a circle in the die
table both the die and the punches rotate together
during operation of the machine
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
66
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
67 The powder is held in a hopper whose
lower opening is located just above the die table
The powder flows on to the die table amp fed into the die by a feed frame
During powder compression both punches operate by vertical movement
After tablet ejection the tablet is knocked away as the die passes the feed frame
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
68 Reference Text book of physical pharmacy by Tripathi pg no
210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of
high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88
Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917
The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543
69
69
Recommended