POWDERSPOWDERS

Powders as a Dosage Powders as a Dosage FormForm

Powders are prepared either as dusting Powders are prepared either as dusting

powders which are applied locally, dentifrices, powders which are applied locally, dentifrices,

products for reconstitution, insufflations and products for reconstitution, insufflations and

aerosols. aerosols.

Advantages of Powders as a dosage Advantages of Powders as a dosage

form:form:

Flexibility in compounding and good chemical Flexibility in compounding and good chemical

stability.stability.

Disadvantages of powders as a dosage Disadvantages of powders as a dosage

form:form:

• Time-consuming to prepareTime-consuming to prepare

• Not suited well for dispensing the unpleasant-Not suited well for dispensing the unpleasant-

tasting or tasting or

hygroscopic drugs.hygroscopic drugs.

• Inaccuracy of dose for bulk powders. Inaccuracy of dose for bulk powders.

The dose is influenced by many factors, including The dose is influenced by many factors, including

size of measuring spoonsize of measuring spoon, , density of powderdensity of powder, ,

humidityhumidity, , degree of settlingdegree of settling and and fluffinessfluffiness due to due to

agitation. agitation.

Preparation of powder dosage formsPreparation of powder dosage forms

Size reductionSize reduction

Reduction of particle size of all ingredients with Reduction of particle size of all ingredients with

the the same rangesame range to prevent separation of large and to prevent separation of large and

small particles.small particles.

When granular or crystalline materials are to be When granular or crystalline materials are to be

incorporated into a powdered product, these incorporated into a powdered product, these

materials are triturated individually and then materials are triturated individually and then

blended together in the mortar.blended together in the mortar.

TriturationTriturationThis term refers to the This term refers to the

process of reducing process of reducing

substances to fine particles substances to fine particles

by rubbing them in a mortar by rubbing them in a mortar

with a pestle. This results in with a pestle. This results in

blending powders and blending powders and

breaking up soft aggregates breaking up soft aggregates

of powders. of powders.

Pulverization by InterventionPulverization by Intervention

This is the process of reducing the state of solids This is the process of reducing the state of solids

with the additional material as volatile solvents with the additional material as volatile solvents

which can be removed easily after the pulverization which can be removed easily after the pulverization

has been completed and the powdered material is has been completed and the powdered material is

obtained.obtained.

This technique is applied to substances which are This technique is applied to substances which are

gummy and tend to reagglomerate or which resist gummy and tend to reagglomerate or which resist

grinding. grinding.

Example:Example:CamphorCamphor which cannot be pulverized easily which cannot be pulverized easily

by by

trituration because of its gummy properties, can trituration because of its gummy properties, can

be be

reduced to a fine powder by the addition of a reduced to a fine powder by the addition of a

small small

amount of amount of alcoholalcohol or other or other volatile solventvolatile solvent. . Iodine crystals Iodine crystals can be triturated with the aid of a can be triturated with the aid of a

small small

quantity of quantity of etherether. .

LevigationLevigation

In this process a paste is first formed by the In this process a paste is first formed by the

addition of a suitable non-solvent to the solid addition of a suitable non-solvent to the solid

material. material.

Particle-size reduction then is accomplished by Particle-size reduction then is accomplished by

robbing the paste in a mortar with a pestle.robbing the paste in a mortar with a pestle.

Levigation technique is used to incorporate solids Levigation technique is used to incorporate solids

into ointments and suspensions.into ointments and suspensions.

Blending (Mixing)Blending (Mixing)

Blending is used when two or more substances are Blending is used when two or more substances are

to be combined to form a uniform powder mixture.to be combined to form a uniform powder mixture.

Depending upon the Depending upon the naturenature of the ingredients and of the ingredients and

the the amountamount of powder to be prepared mixing may be of powder to be prepared mixing may be

byby spatulation, trituration, sifting, tumbling spatulation, trituration, sifting, tumbling or by or by

mechanical mixers.mechanical mixers.

This method is used when This method is used when small amounts small amounts of powders of powders

are to be blended by the movement of a spatula are to be blended by the movement of a spatula

through the powders on a sheet of paper or an through the powders on a sheet of paper or an

ointment slab.ointment slab.

SpatulationSpatulationSpatulationSpatulation

TriturationTriturationTriturationTrituration

The method may be employed The method may be employed

both to reduce and mix both to reduce and mix

powders.powders.

Porcelain or Wedgewood Porcelain or Wedgewood

mortar is mortar is

used.used.

For chemicals that may stain For chemicals that may stain

the the

porcelain or Wedgewood porcelain or Wedgewood

surface, surface,

a glass mortar may be a glass mortar may be

preferred. preferred.

When potent substances are to be mixed with a When potent substances are to be mixed with a

large amount of diluent, large amount of diluent, geometric dilution methodgeometric dilution method

is is employed to ensure the uniform distribution of the employed to ensure the uniform distribution of the

potent drug. potent drug.

By this method, the potent drug placed upon an equal volume

the diluent in a mortar and the mixture is mixed by trituration.

Then a second portion of diluent equal in volume to the powder

mixture in the mortar is added, and the trituration is repeated.

This process is continued by adding equal volumes of diluent to

that powder present in the mortar and repeating the mixing

until all of the diluent is incorporated.

Powders may also be mixed by passing them Powders may also be mixed by passing them

through sifters. through sifters.

This process results in a light fluffy product. This process results in a light fluffy product.

This process is This process is not acceptablenot acceptable

for the incorporation of for the incorporation of

potent drugs into a diluent base. potent drugs into a diluent base.

SiftingSiftingSiftingSifting

TumblingTumblingTumblingTumbling

The powder enclosed in a large container which The powder enclosed in a large container which

rotates generally by a motorized process.rotates generally by a motorized process.

Such blenders are widely employed in industry to Such blenders are widely employed in industry to

blend large amounts of powder.blend large amounts of powder.

Problems in powder manufacture Problems in powder manufacture

The incorporation of The incorporation of volatilevolatile

substances, substances, eutecticeutectic mixtures, mixtures,

liquidliquids and s and hygroscopichygroscopic

substances into powders presents substances into powders presents

problems that require special problems that require special

treatments.treatments.

The loss of camphor, menthol and The loss of camphor, menthol and

essential oils by volatilization when essential oils by volatilization when

incorporated into powders may be incorporated into powders may be

prevented or retarded by use of prevented or retarded by use of heat-heat-

sealed plastic bags sealed plastic bags or by or by double double

wrapping wrapping with a waxed or glassine paper with a waxed or glassine paper

inside a bond paper.inside a bond paper.

Volatile SubstancesVolatile Substances

Liquids result from the Liquids result from the

combination of phenol, camphor, combination of phenol, camphor,

menthol, thymol, antipyrne, menthol, thymol, antipyrne,

phenacetin, acetanilid, aspirin, phenacetin, acetanilid, aspirin,

salol at ordinary temperatures.salol at ordinary temperatures.

Eutectic Mixtures

These eutectic mixtures can be incorporated into These eutectic mixtures can be incorporated into

powders by addition of an inert diluent or powders by addition of an inert diluent or

absorbent. absorbent.

kaolin, starch, bentonite are used as absorbents kaolin, starch, bentonite are used as absorbents

Incorporation of 20% silicic acid (particle size, 50 Incorporation of 20% silicic acid (particle size, 50

µm) µm)

prevented eutexia with aspirin, phenyl salicylate. prevented eutexia with aspirin, phenyl salicylate.

This technique offers the advantage of extended This technique offers the advantage of extended

product stability. product stability.

Magnesium carbonate or light magnesium oxideMagnesium carbonate or light magnesium oxide

are used commonly as effective diluents for this are used commonly as effective diluents for this

purpose. An amount of diluent equal to the eutectic purpose. An amount of diluent equal to the eutectic

compounds is sufficient to prevent liquefaction for compounds is sufficient to prevent liquefaction for

about 2 weeks.about 2 weeks.

Each eutectic compound should be mixed first with Each eutectic compound should be mixed first with

a portion of the diluent and gently blended together, a portion of the diluent and gently blended together,

preferably with a spatula on a sheet of paper. preferably with a spatula on a sheet of paper.

Liquids may be incorporated into divided powders. Liquids may be incorporated into divided powders.

Magnesium carbonate, starch or lactose may be Magnesium carbonate, starch or lactose may be

added added

to increase the absorbability of the powders if to increase the absorbability of the powders if

necessary. necessary.

When the liquid is a solvent for a nonvolatile heat-When the liquid is a solvent for a nonvolatile heat-

stable stable

compound, it may be evaporated gently on a water compound, it may be evaporated gently on a water

bath. bath.

LactoseLactose may be added during the evaporation to may be added during the evaporation to

increase increase

the rate of solvent loss by increasing the surface the rate of solvent loss by increasing the surface

area. area. Some extracts and tinctures may be treated in Some extracts and tinctures may be treated in

this manner, although the use of an equivalent this manner, although the use of an equivalent

amount of a powdered extract is a more desirable amount of a powdered extract is a more desirable

technique.technique.

Liquids

Substances that become moist because of affinity Substances that become moist because of affinity

for for

moisture in the air may be prepared as moisture in the air may be prepared as divided divided

powders powders

by adding by adding inert diluentsinert diluents..

Double-wrappingDouble-wrapping is desirable for further is desirable for further

protection. protection.

ExtremelyExtremely Hygroscopic compounds Hygroscopic compounds cannotcannot be be

prepared prepared

as powders.as powders.

Hygroscopic Substances

Use and Packaging of PowdersUse and Packaging of Powders

Depending upon their use, powders are Depending upon their use, powders are

packaged and dispensed in two main packaged and dispensed in two main

ways:ways:

Bulk powders.

Divided powders.

Example of the bulk powders are:Example of the bulk powders are:

Oral powders:Oral powders: as antacid and laxative powders, as antacid and laxative powders,

it can be taken by mixing an amount of powder it can be taken by mixing an amount of powder

in a portion of water or other beverage and in a portion of water or other beverage and

swallowing as solution or suspension.swallowing as solution or suspension.

Douche powdersDouche powders: generally dissolved in warm : generally dissolved in warm

water and used as antiseptics or cleansing water and used as antiseptics or cleansing

agents for a body cavity as for vaginal use.agents for a body cavity as for vaginal use.

Douche powders are Dispensed in wide-mouth Douche powders are Dispensed in wide-mouth

glass jars serves to protect against air and glass jars serves to protect against air and

moisture or loss of volatile materials moisture or loss of volatile materials

BULK POWDERSBULK POWDERS

• Dusting Powders are usually dispensed in sifter Dusting Powders are usually dispensed in sifter

containers for convenient application to the containers for convenient application to the

skin.skin.

• Foot powders and talc powders are currently Foot powders and talc powders are currently

available available

as aerosols.as aerosols.

Dentifrices:Dentifrices: Dental cleansing powders, used in Dental cleansing powders, used in

dental hygiene. dental hygiene.

Denture powders, some used as dentifrices and Denture powders, some used as dentifrices and

others as adhesives to hold the dentures in others as adhesives to hold the dentures in

place.place.

Dusting Powders:Dusting Powders: Medicated or non- Medicated or non-

medicated for external application for medicated for external application for

various parts of the body as various parts of the body as

lubricants, protectives, absorbents, lubricants, protectives, absorbents,

antiseptics, antiseptics,

astringents and antiperspirants astringents and antiperspirants

agents.agents.

All powders should be stored in tightly closed All powders should be stored in tightly closed

containers containers

for Protection against humidity, air oxidation and for Protection against humidity, air oxidation and

loss of loss of

volatile ingredients.volatile ingredients.

Dispensing powdered drugs in bulk amounts Dispensing powdered drugs in bulk amounts

limited to limited to

non-potent substances.non-potent substances.

Powders containing Powders containing potent substances potent substances or those that or those that

should be administered in should be administered in controlled dosage controlled dosage

are are

Supplied to the patient in Supplied to the patient in divided amountsdivided amounts. .

After the powder has been mixed, it mayAfter the powder has been mixed, it may

be divided into individual doses.be divided into individual doses.

Each divided portion of powder may be placed on Each divided portion of powder may be placed on

a a

small piece of paper or metal foil which is then small piece of paper or metal foil which is then

folded or folded or

in small heat-sealed plastic bags so as to enclose in small heat-sealed plastic bags so as to enclose

the the

medication. medication.

Hygroscopic and volatile drugs canHygroscopic and volatile drugs can

be protected by using a waxed paper; be protected by using a waxed paper;

divided POWDERSdivided POWDERS

Pharmaceutical powders may be classified as free-Pharmaceutical powders may be classified as free-

flowing or cohesive (non-free-flowing). flowing or cohesive (non-free-flowing).

Flow properties are significantly affected by Flow properties are significantly affected by

changes in changes in

particle sizeparticle size, , densitydensity, , shapeshape, , electrostatic chargeelectrostatic charge, ,

and and

adsorbed moistureadsorbed moisture, which may arise from , which may arise from

processing or processing or

formulation.formulation.

Preformulation, powder flow should be Preformulation, powder flow should be

determined for determined for

the improvement of pharmaceutical formulation the improvement of pharmaceutical formulation

and and

consequences of processing.consequences of processing.

This subject becomes vital for the development of This subject becomes vital for the development of

a a

commercial solid dosage form containing a large commercial solid dosage form containing a large

percentage of cohesive material.percentage of cohesive material.

1-1- Particle size:Particle size: Frictional and Frictional and

cohesive forces (resistance to cohesive forces (resistance to

flow) are increased as the particle flow) are increased as the particle

size is reduced . size is reduced .

Very fine particles do not flow as large particles. Very fine particles do not flow as large particles.

In general, particles in the size range of In general, particles in the size range of 250-2000 250-2000

µµ flow flow freelyfreely if the shape is agreeable. Particles in if the shape is agreeable. Particles in

the size range of the size range of 75-250 µ75-250 µ may flow may flow freelyfreely or or

cause problemscause problems, depending on shape and other , depending on shape and other

factors. With particles factors. With particles less than 100 µless than 100 µ in size, flow in size, flow

is is a problema problem. .

Factors affecting Powder Factors affecting Powder

Flowability:Flowability:

2-2- Density and porosity:Density and porosity: - -

Particles with high density and Particles with high density and

low porosity tend to posses free low porosity tend to posses free

flowing properties.flowing properties.

3- 3- Particle shape:Particle shape: Rough Rough

irregular particles presents more irregular particles presents more

points of contact than smooth points of contact than smooth

spherical particles thus Spherical spherical particles thus Spherical

particles flow better than needles.particles flow better than needles.4- 4- Particle size distribution:Particle size distribution: Larger amount of Larger amount of

fines can inhibit poor flowing. fines can inhibit poor flowing.

5- 5- Moisture content:Moisture content: Drying the powders will Drying the powders will

reduce the cohesiveness.reduce the cohesiveness.

Flow rate determination Flow rate determination • Powder flows through an orifice onto Powder flows through an orifice onto

an electronic balance.an electronic balance.

• Flow rate is determined by measuring weight of Flow rate is determined by measuring weight of

powder powder

pass through an orifice per time (g/sec).pass through an orifice per time (g/sec).

• Several flow rate determinations through a variety Several flow rate determinations through a variety

of of

orifice sizes (1/8 to 1/2 inches) should be made.orifice sizes (1/8 to 1/2 inches) should be made.

• In general, the greater the standard deviation In general, the greater the standard deviation

between between

multiple flow rate measurements, the greater is multiple flow rate measurements, the greater is

the the

weight variation in products produced from that weight variation in products produced from that

powder. powder.

Particle Size AnalysisParticle Size Analysis

The particles of pharmaceutical powders may be The particles of pharmaceutical powders may be

coarse to extremely fine.coarse to extremely fine.

Standard Sieve Shaker

The USP utilizes terms which are The USP utilizes terms which are

related to the proportion of related to the proportion of

powder that is capable of powder that is capable of

passing through the openings of passing through the openings of

standardized sieves of varying standardized sieves of varying

dimensions in a specified time.dimensions in a specified time.

Opening of Standard SievesOpening of Standard Sieves

Sieve NumberSieve NumberSieve Sieve OpeningOpening

22 9.5 mm9.5 mm3.53.5 5.6 mm5.6 mm

444.75 mm4.75 mm882.36 mm2.36 mm

10102.00 mm2.00 mm2020850 µm850 µm3030600 µm600 µm4040425 µm425 µm5050300 µm300 µm6060250 µm250 µm7070212 µm212 µm8080180 µm180 µm

100100150 µm150 µm120120125 µm125 µm200200 75 75 µmµm230230 63 µm63 µm270270 53 µm53 µm325325 45 µm45 µm400400 38 µm38 µm

Sieve AnalysisSieve Analysis

Coarse powderCoarse powder - -All particles pass through All particles pass through

No. 20 sieve and not more 60% through No. 40 No. 20 sieve and not more 60% through No. 40

sieve.sieve.

Moderately Coarse powderModerately Coarse powder - -All particles pass All particles pass

through No. 40 sieve an not more than 60% through No. 40 sieve an not more than 60%

through No. 60 sievethrough No. 60 sieve

Fine powderFine powder - -All particles pass through No. 80 All particles pass through No. 80

sieve. There is no limit as to greater fineness.sieve. There is no limit as to greater fineness.

Very Fine powderVery Fine powder - -All particles pass through No. All particles pass through No.

120 sieve. There is no limit as to greater fineness.120 sieve. There is no limit as to greater fineness.

Methods of particle size determinations include Methods of particle size determinations include

techniques that provide average particle size by:techniques that provide average particle size by:

WeightWeight ( (sieve method, light scattering, sieve method, light scattering,

sedimentation sedimentation

methodmethod).).

VolumeVolume ( (light scattering, electronic sensing zone, light scattering, electronic sensing zone,

light light

obstruction, air permeation and the obstruction, air permeation and the

optical optical

microscopemicroscope).).

Methods for the determination of particle size:Methods for the determination of particle size:Methods for the determination of particle size:Methods for the determination of particle size:

Sieving:Sieving: In which particles are In which particles are

passed by mechanical shaking passed by mechanical shaking

through a series of sieves of through a series of sieves of

known and successively smaller known and successively smaller

size and the determination of size and the determination of

the proportion of powder the proportion of powder

passing through or being held passing through or being held

on each sieve (range: from on each sieve (range: from

about 50 to 3360 micrometers, about 50 to 3360 micrometers,

depending upon sieve sizes).depending upon sieve sizes).Sieve AnalysisSieve Analysis

Microscopy:Microscopy: In which the particles are sized In which the particles are sized

through the use of a calibrated network through the use of a calibrated network

background (range: 0.2 to 100 micrometers)background (range: 0.2 to 100 micrometers)

                  

                

Sedimentation :Sedimentation :

Particle size is determined by measuring the Particle size is determined by measuring the

settling velocity of particles through a liquid settling velocity of particles through a liquid

medium in a gravitational or centrifugal medium in a gravitational or centrifugal

environment.environment.

Sedimentation rate may be calculated from Sedimentation rate may be calculated from Stokes' Stokes'

law law

Using the "Andreasen Pipet.“Using the "Andreasen Pipet.“

The Andreasen pipet is designed where a sample The Andreasen pipet is designed where a sample

can be removed from the lower portion at selected can be removed from the lower portion at selected

time intervals. The powder is dispersed in a time intervals. The powder is dispersed in a

nonsolvent in the Andreasen Pipet.nonsolvent in the Andreasen Pipet.

Agitated, and 20 mL samples removed over a period Agitated, and 20 mL samples removed over a period

of time. of time.

Each 20 mL sample is dried and weighed.Each 20 mL sample is dried and weighed.

Light energy diffraction:Light energy diffraction:

Particle size is determined by the reduction in light Particle size is determined by the reduction in light

reaching the sensor when the particles, dispersed in a reaching the sensor when the particles, dispersed in a

liquid or gas, passes through the sensing zone. liquid or gas, passes through the sensing zone.

Laser holography:Laser holography:

in which a pulsed laser is fired in which a pulsed laser is fired

through an aerosolized particle through an aerosolized particle

spray and photographed in three spray and photographed in three

dimensions with a holographic dimensions with a holographic

camera, camera,

Angles of Repose Angles of Repose

ФФ The angle of repose is a relatively simple The angle of repose is a relatively simple

technique for estimating the flowability of a technique for estimating the flowability of a

powder.powder.

Such measurements give at least a qualitative Such measurements give at least a qualitative

assessment of the internal cohesive and assessment of the internal cohesive and

frictional effects under low levels of external frictional effects under low levels of external

loading, as might apply in powder mixing, or in loading, as might apply in powder mixing, or in

tablet die or capsule shell filling operations.tablet die or capsule shell filling operations.

The height and diameter of the resulting cone is The height and diameter of the resulting cone is

measured. measured.

It is the maximum angle that can be obtained between It is the maximum angle that can be obtained between

the free standing surface of a powder heap and the the free standing surface of a powder heap and the

horizontal plane.horizontal plane.

The angle of reposeThe angle of repose can be can be

determined experimentally by determined experimentally by

allowing a powder to flow through allowing a powder to flow through

a funnel and fall freely onto a a funnel and fall freely onto a

surface. surface.

D

h2Tan Tan ФФ = =

Angle of repose Angle of repose ФФ can be defined by the equation: can be defined by the equation:

Where:Where:

hh is the height of the powder cone. is the height of the powder cone.

DD is the diameter of the powder cone. is the diameter of the powder cone. Values of Values of ФФ between 20° - 40° indicate between 20° - 40° indicate

reasonable flow.reasonable flow.

Powders with low angles of repose will flow Powders with low angles of repose will flow

freelyfreely

Above 50° the powder flows only with great Above 50° the powder flows only with great

difficulty.difficulty.

Mass-Volume Mass-Volume RelationshipsRelationships

The mass of a bulk powder can be accuracy The mass of a bulk powder can be accuracy

determined determined

but measurement of the volume is more but measurement of the volume is more

complicated. complicated.

The main problem arises in measuring the volume The main problem arises in measuring the volume

of of

bulk powders is the presence of three types of air bulk powders is the presence of three types of air

spaces or voids between particles. spaces or voids between particles.

1.1.Open intraparticulate voids:-Open intraparticulate voids:-

Those within a single particle but open to the Those within a single particle but open to the

external external

environment.environment.

2.2. Closed intraparticulate voids:-Closed intraparticulate voids:-

Those within a single particle but closed to the Those within a single particle but closed to the

external external

environment.environment.

3. Interparticulate voids:-3. Interparticulate voids:-

The air spaces between individual particles.The air spaces between individual particles.

Therefore, at least three interpretations of Therefore, at least three interpretations of

"powder volume may be proposed "powder volume may be proposed

The true volume (VThe true volume (Vtt):):

The total volume of the solid particles, which The total volume of the solid particles, which

excludes all excludes all

spaces greater than molecular dimensions, and spaces greater than molecular dimensions, and

which has which has

a characteristic value for each material.a characteristic value for each material.

The granular volume (particle volume)The granular volume (particle volume) (V(Vgg):):

The cumulative volume occupied by the particles, The cumulative volume occupied by the particles,

including all intraparticulate (but not including all intraparticulate (but not

interparticulate) interparticulate)

voids. voids.

The bulk volume (VThe bulk volume (Vbulkbulk):):

The total volume occupied by the entire powder The total volume occupied by the entire powder

mass mass

under the particular packing achieved during the under the particular packing achieved during the

measmeas

POROSITY, VOID AND BULK POROSITY, VOID AND BULK

VOLUMEVOLUMEPacking and flow of powders are important for:Packing and flow of powders are important for:

Impacting the size of container required for Impacting the size of container required for

packagingpackaging

The flow of granulationsThe flow of granulations

The efficiency of the filling apparatus during the The efficiency of the filling apparatus during the

tablettingtabletting

Encapsulating process. Encapsulating process.

A number of characteristics can be used to A number of characteristics can be used to

describe powders including:describe powders including:

Porosity, true volume, bulk volume, apparent Porosity, true volume, bulk volume, apparent

density, true density, and bulkiness. density, true density, and bulkiness.

The void is the space between the particles which The void is the space between the particles which

resulting in a porosity. resulting in a porosity.

If particles are not uniform, the smaller particles will If particles are not uniform, the smaller particles will

slip into the void spaces between the larger slip into the void spaces between the larger

particles and decrease the void areas.particles and decrease the void areas.

The Void =The Void = Where:Where:

Bulk Volume, Bulk Volume, V V bulkbulk = The volume occupied by a = The volume occupied by a

selected selected

weight of a powder. weight of a powder.

The True volume, The True volume, VVtt = The space occupied by the = The space occupied by the

powder powder

exclusive of spaces greater exclusive of spaces greater

than than

the intramolecular space.the intramolecular space.

The PorosityThe Porosity = X = X 100 100

The bulk volume = True volume + PorosityThe bulk volume = True volume + Porosity

APPARENT DENSITY, TRUE DENSITY AND APPARENT DENSITY, TRUE DENSITY AND

BULKINESS BULKINESS

Bulk densityBulk density is of great importance for is of great importance for capsule capsule

filling, tablet Compressibilityfilling, tablet Compressibility and for the and for the

homogeneity of formulation in which there are homogeneity of formulation in which there are

large differences in drug and excipient densities.large differences in drug and excipient densities.

Apparent bulk density (g/ml) is determined by Apparent bulk density (g/ml) is determined by

pouring presieved (40-mesh) bulk drug into a pouring presieved (40-mesh) bulk drug into a

graduated cylinder via a large funnel and graduated cylinder via a large funnel and

measuring the volume and weight "as is." measuring the volume and weight "as is."

The Apparent Density The Apparent Density PPaa== bulkV

theSampleofWeight

The True Density PThe True Density P ==V

theSampleofWeight

The bulkiness, BThe bulkiness, B = is the reciprocal = is the reciprocal

of the apparent densityof the apparent densityB = 1 /paB = 1 /pa

Powders with low apparent density and large bulk Powders with low apparent density and large bulk

volume are "light" powders, and those with high volume are "light" powders, and those with high

apparent density and small bulk volume are "heavy" apparent density and small bulk volume are "heavy"

powders.powders.

Tapped densityTapped density is determined by placing a is determined by placing a

graduated cylinder containing a known mass of drug graduated cylinder containing a known mass of drug

or formulation on a mechanical tapper apparatus, or formulation on a mechanical tapper apparatus,

which is operated for a fixed number of taps (≈1000) which is operated for a fixed number of taps (≈1000)

until the powder bed volume has reached a until the powder bed volume has reached a

minimum. minimum.

Using the weight of drug in Using the weight of drug in

the cylinder and this the cylinder and this

minimum volume, tapped minimum volume, tapped

density can be determined.density can be determined.

Where:Where:

PPtt = The tapped bulk density = The tapped bulk density

PP00 = The initial bulk density= The initial bulk density

Compressibility

% Compressibility = X % Compressibility = X 100100

t

ot

P

PP

A simple indication of the flow property of a powder A simple indication of the flow property of a powder

is given by using of is given by using of compressibility index (I)compressibility index (I)

Where:Where:

VV = the volume occupied by a sample of the powder = the volume occupied by a sample of the powder

after after

tapping proceduretapping procedure

VVoo = the volume before tapping. = the volume before tapping.

Values of I below 15% usually give rise to good flow Values of I below 15% usually give rise to good flow

characteristics, but above 25% indicate poor characteristics, but above 25% indicate poor

flowability.flowability.

Compressibility index (I) = X 100Compressibility index (I) = X 100

01V

V