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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