Lesson - 9
Tablets-I
Introduction
-Dr Ajay Semalty
Department of Pharmaceutical Sciences,
H.N.B Garhwal University (A Central University)
Srinagar Garhwal-246174
Learning outcomes
After learning this module, you will be able to understand
What is tablet and what are its advantages and disadvantages
Types and Classification of tablets.
What is granulation, why it is important, and how it is done for tablet
manufacturing
Lesson Plan
Definition and ideal properties
Advantages, Disadvantages, and Classification of tablets.
Types and classification of excipients
Basic steps of Formulation of tablets,
Granulation methods: process, factors and equipment
o Wet Granulation (WG)
o Dry Granulation (DG)
Module 9 Tablets – I 2
MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal
University (A Central University) Srinagar (Garhwal) Uttarakhand, India
Tablets
Tablets are the most common and convenient dosage form. About 70%
of the total medicines are in Tablet form.
“Tablets are solid, flat or biconvex dishes, unit dosage form,
prepared by compressing a drug or a mixture of drugs, with or
without diluents.”
Do you know what unit dosage form is? The dosage form which
deliver one single unit of dosage of the drug. Tablet is a unit
dosage form. Dear learners can you let me know any other
example of unit dosage form? And multi-unit dosage form?
Ideal Characteristics of Tablets
A tablet should have the following ideal properties.
Elegant product identity
Free of defects like chips, cracks, discoloration, and
contamination
Sufficient strength (to withstand mechanical shock and
agitation during its production, packaging, shipping and
dispensing.
Chemical stability: shelf life
Physical stability: color, physical integrity like shape etc.
Release the drug in desired and reproducible manner.
Advantages of Tablet Dosage Forms
Tablet has a number of advantages, one of the major advantage
over capsule, is that tablet is an essentially tamperproof doses form.
Other potential advantages of tablets are as followed:
Module 9 Tablets – I 3
MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal
University (A Central University) Srinagar (Garhwal) Uttarakhand, India
These are the unit dosage forms which offer the greatest
flexibility (with respect to doses) of all oral doses forms.
Its cost is lowest of all oral dosage forms.
These are the lightest and most compact of all oral doses
forms.
These are in general the easiest and cheapest to package and
ship of all oral dosage forms.
Product identification is simplest and cheapest, requiring no
additional processing steps.
These may provide the greatest ease of swallowing with least
tendency for ''hang-up' above stomach, especially when coated,
provided that tablet disintegration is not excessively rapid.
These are better suited to large scale production than other unit
oral forms.
These have best combined properties of chemical, mechanical,
and microbiological stability of all the oral forms.
Objectionable odor and bitter taste can be masked by coating
technique.
Generally more stable than liquids with longer expiration
dates.
Release rate of the drug from tablet can be tailored to meet
pharmacological requirements.
Disadvantages of Tablet Dosage Form
Drugs which are destroyed in stomach cannot be prepared in
tablets e.g proteins/peptides etc.
Drugs with bitter taste or odour cannot be formulated in tablets
without modification (capsules may be tried)
Peak and valley effect in plasma time concentration curve for
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MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal
University (A Central University) Srinagar (Garhwal) Uttarakhand, India
IR dosage forms
The drug with too short half life can not be formulated.
Classification of Tablets (USP)
I. Immediate-release tablet
Disintegrating tablet (conventional tablet)
Chewable tablets
Effervescent tablets
Sublingual and Buccal tablets
Lozenges
II. Modified-release tablet
Extended-release
Delayed-release
I. Immediate-release tablet
Conventional/Disintegrating tablet
It is the most common type of tablets. It is released rapidly after
administration. It is intended to be swallowed and undergo
disintegration and dissolution in the GIT. The commonly required
excipients in these are filler (with low dose drug), disintegrant,
binder, glidant, lubricant and antiadherent.
Chewable tablets
These tablets are designed for children and elderly people and can be
taken without water. The tablet is to be chewed and thus
mechanically disintegrated in the mouth, so that no disintegrant is
included in its composition. Its important excipients are Flavoring,
sweetening and coloring agents. e.g. Chewable Antacid tablets
Effervescent tablets
The effervescent tablet is dropped into a glass of water before
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University (A Central University) Srinagar (Garhwal) Uttarakhand, India
administration during which Carbon di oxide (CO2) is liberated. It
can be taken without water. It facilitates rapid tablet disintegration
and drug dissolution. The special packaging is needed to avoid
exposure of these tablets to moisture. It is used to obtain rapid
drug action e.g Effervescent antacid tablets. The important
excipients of these tablets are acid with alkali effervescing
compound, flavoring, and coloring agents
Sublingual and Buccal tablets
They are used for drug release in mouth for systemic delivery by
avoiding first pass metabolism. Here the drug diffuses into the
blood, directly through tissues under the tongue in case of
sublingual tablets and through oral mucosa in case of buccal
tablets. It facilitates rapid tablet disintegration and drug
dissolution. For example, Nitroglycerin sublingual tablet exerts its
action within two minutes for rapid relief of "Angina pectoris"
attack, because the sublingual area is rich in blood supply.
Nitroglycerine suffers from first-pass metabolism if taken orally.
Lozenges
These are the tablets which dissolve slowly in the mouth. These are
used for local medications in the mouth or throat, e.g. local
anesthetics, antiseptics and antibiotics and for systemic drug
uptake. In the lozenges no disintegrant is included. Other
additives (binder and filler) must have pleasant taste.
Modified-Release Tablets
According to the USP/NF the term 'modified release dosage forms' is
defined as “one for which the drug release characteristics of
time course and/or location are chosen to accomplish
therapeutic objectives not offered by the conventional dosage
forms.”
Module 9 Tablets – I 6
MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal
University (A Central University) Srinagar (Garhwal) Uttarakhand, India
Classification
Modified release dosage forms may be classified into two types.
Extended-release
Delayed release
Extended-release Tablets
It is defined as the one that allows at least a twofold reduction in the
dosing frequency as compared to that of conventional (immediate
release) dosage form. For example: controlled release or sustained
release tablets
Delayed release Tablets
“the dosage form that releases a discrete portion or portions of drug at
a time (or times) other than promptly after administration.” -
USP
Enteric coated tablets are the example of delayed release dosage forms
Fig. Plasma Concentration Time profile Curve for Immediate release and Modified
Release dosage form
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MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal
University (A Central University) Srinagar (Garhwal) Uttarakhand, India
Excipients
“An excipient is an inactive substance used as a carrier for the active
ingredients of a medication”.
The excipients are selected on the basis nature of drug, nature of other
excipients, compatibility with drug and other excipients and the
desired release or performance characteristics of tablet.
Classification of excipients
A. Primary Excipients: The primary excipients impart satisfactory
compression characteristics to the formulation. E.g. diluents,
binders, glidants and lubricants
B. Secondary Excipients: The secondary excipients give additional
desirable physical characteristics to the finished tablet. e.g.
disintegrants, coloring, flavoring and sweetening agents.
Filler / diluent
Filler or diluents add bulk to the tablet for compression and easy
handling. Diluents weigh 10 to 20 fold of the dosage of API. E.g.
Glucose, Sodium chloride, Sucrose, Mannitol (chewable tablet, freely
soluble in water, cool taste), Microcrystaline Cellulose (excellent
compression property, highly stable and disintegrating property).
Binder
Do you remember why we need cement to build a house? Binder is
added for cohesive strength after compression. e.g. Aacacia
mucilage, Glucose, Gelatin, providone (PVP), Starch mucilage
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University (A Central University) Srinagar (Garhwal) Uttarakhand, India
Disintegrant
Figure: Importance of disintegration
Tablet is needed to be dissolved in GI fluid for getting absorbed
and for getting dissolved it is needed to be disintegrate in smaller
particles. The disintegrants make the tablet to break down in
smaller particles after oral ingestion.
E.g. crospovidone, croscarmellose sodium, sodium starch glycolate
etc.
Glidant
Glidants are used for reducing the friction between particles. Glidants
improve the flow properties of tablet granules and powders during
processing (mixing, moving for compression etc). e.g. Corn starch,
Talc, Colloids silicates.
Lubricant
Lubricants ensure that tablet possess a smooth surface. Lubricants act
by reducing the friction between tablet wall and die walls. e.g.
Talc, stearic acid, silicates.
Antiadherent
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University (A Central University) Srinagar (Garhwal) Uttarakhand, India
The antiadherents stop the powder from sticking to the equipment as
the tablet is being made. Exp- Talc, Magnesium stearate, Starch
derivatives.
Miscellaneous
Colors, flavors etc.
Manufacturing Tablet
Tablet is the most complex Dosage form. The tablet manufacturing is
an art as well as a science. It consists of the two important steps:
Step1: Blending of drug with excipients (mixing and granulating)
and;
Step 2: compression (by punches onto die cavity)
Direct compression (skipping granulation) may be practiced for drug
and excipients with good compatibility and low stickiness (but not
always feasible)
Mixing and granulation
“Granulation is the process of combining particles together by creating
bonds between them”
The definition is looking typical? Let me make it simpler for you
Have you seen preparation of besan laddu?
Coarse besan or fine besan?
Why the coarse besan is needed ? Because it has the good binding.
Objectives of granulation
Conversion Powder to granules is granulation and it is performed with
the following objectives.
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University (A Central University) Srinagar (Garhwal) Uttarakhand, India
To assure an even distribution of the active compound in the
final tablet
To ensure content uniformity due to narrow size range
To increase the density for easy storage and shipment
To improve flow and compaction
There are several different methods of granulation. The most popular,
which is used by over 70% of formulation in tablet manufacture is
wet granulation. Dry granulation is another method used to form
granules.
Mechanism of granulation
The granulation occurs due to following events.
Wetting
Nucleation
Coalescence/ growth
Consolidation
Attrition/ breakage
By solid bridges/ chemical reaction/ sintering/ crystalization/
deposition of particles/ adhesive and cohesive forces of High
viscous binders
Wet Granulation
Imagine preparing dough for chapati
What do you need for that?
Yes…water in optimum amount
“using a liquid binder (in optimum amount) to lightly agglomerate the
powder mixture”
Wet granulation is a process of using a liquid binder to lightly
agglomerate the powder mixture. The amount of liquid has to be
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MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal
University (A Central University) Srinagar (Garhwal) Uttarakhand, India
properly controlled, as over-wetting will cause the granules to be too
hard and under-wetting will cause them to be too soft and friable.
Aqueous solutions have the advantage of being safer to deal with than
solvent based systems.
Fig. The wet Granulation Process
Fluidized bed granulation (FBG)
FBG is a multiple step wet granulation process. It is All in one
process: pre-heat, granulate, and dry the powders. It allows close
Weigh active ingredient and
excipients
Add the liquid binder to the powder blend and mix thoroughly
Screen the damp mass through a
mesh to get pellets/granules
Drying
Again passed through a sieve (Finer one than
earlier used)
Granules
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University (A Central University) Srinagar (Garhwal) Uttarakhand, India
control of the granulation process.
It’s a huge equipment and it is used in mixing/granulation, drying and
film coating. The lower part contains a perforated basket of SS which
contains the mixture to be granulated. The air enters from the bottom
of the perforated basket. The particles are uplifted with the stream of
air. The fountain like movement of particles is called Wurster process.
The granulating fluid is sprayed (Top/bottom or tangential spray). At a
stage the bed of solid become fluidized and behaves like fluid. Hence
it is called FBG or FBD.
Factors affecting granulation
Blend factors: Particle size of the drug and excipients
Binder factor: Type, Volume and concentration of binder
Granulation process factor: granulation time, equipment and
drying rate
Dry Granulation
Dry granulation is done for moisture and heat sensitive products and
the products which are not compressed well after WG. It is done
without the use of liquid binder. It is simpler than wet granulation
and is a low cost technique. The DG involves creating granules by
light compaction of the powder blend under low pressures. The
prepared slugs are broken into granules.
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MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal
University (A Central University) Srinagar (Garhwal) Uttarakhand, India
Process of DG
Milling (Cutter Mill)
Mixing (Sigma Blade Mixer)
Slugging
Screening (Oscillating Granulator)
Mixing with Disintegrant and Lubricant
Compression
Equipment for granulation
Roller compaction, extrusion spheronization, spray drying
equipment
Low shear/ High shear granulators
Fluidized Bed Dryer (FBD)
Continuous spouted bed
High shear granulator (with the help of counter current
operating blades) E.g. RMG (Rapid Mixer Granulator).
New advanced techniques
Steam Granulation,
Melt Granulation Granulation,
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University (A Central University) Srinagar (Garhwal) Uttarakhand, India
Moisture Activated Dry Granulation (MADG),
Moist Granulation Technique (MGT),
Thermal Adhesion Granulation Process (TAGP),
Extrusion-spheronization (ES),
Continuous twin screw wet granulation (cTSWG)
Table: The advanced techniques in Granulation
Technique Description
Steam Granulation Modification of wet granulation; steam is
used as a binder in place of water
Melt Granulation / Thermoplastic
Granulation
Granulation is done by addition of meltable
binder (binder is in solid state at room
temperature but melts in the temperature
range of 50 – 80˚C).
Moisture Activated Dry Granulation
(MADG)
Minimal moisture addition, distribution and
agglomeration. No drying step is required.
Water distribution is via high shear mixer,
or low-shear mixer with highly atomized
water spray
Moist Granulation Technique (MGT) Works on the principle of MADG. A small
amount granulating fluid is added to
activate dry binder and to facilitate
agglomeration. Then a moisture absorbing
material like Microcrystalline Cellulose
(MCC) is added to absorb any excess
moisture.
Thermal Adhesion Granulation
Process (TAGP)
Used for preparing direct tableting;
performed under low moisture content or
low content of pharmaceutically acceptable
solvent by subjecting a mixture containing
excipients to heating at a temperature in the
range from about 30ºC to 130ºC in a closed
system under mixing by tumble rotation
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University (A Central University) Srinagar (Garhwal) Uttarakhand, India
until the formation of granules.
Foam Granulation Liquid binders are added as aqueous foam.
Extrusion-spheronization
(ES)
Extrusion (forming a raw material into a
product of uniform shape and density by
forming it through an orifice or die under
controlled conditions) followed by
spheronization (a rapid and flexible process
where wet extruded mass is converted to
small spheres) through multi step
processing
Continuous twin screw wet
granulation (cTSWG)
Advanced technique of ES; Preblend of
crystalline poorly soluble API and
amorphous polymer is charged into Twin
screw granulator
Take Away Message
Tablet are unit dosage forms which are the most common, cost
effective, and convenient dosage forms
Tablets may be of different types: IR or modified release.
Various excipients with different functions are needed
Mixing, granulation and compression are three important steps in
manufacturing of tablets.
Wet and dry granulation are two methods of granulation
Further Readings
• Aulton ME (ED), Pharmaceutics: The science of Dosage form design,
II edn, Churchill Livingstone, London, 2002.
• Semalty et al., Essentials of Pharmaceutical Technology, II Edn, 2018,
Pharma Med press, Hyderabad, India
• Qiu Y, Chang Y and Zhang GZ (Exe. Eds), Developing solid oral
dosage forms: Pharmaceutical theory and practice, Elsevier, 2009.
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University (A Central University) Srinagar (Garhwal) Uttarakhand, India
References/ Credits
• USP-40
• Semalty et al., Essentials of Pharmaceutical Technology, II Edn, 2018,
Pharma Med press, Hyderabad, India