Madan Bhandari Academy of Health Sciences

PREPARED BY:
Phr. Manima Maharjan (M. Pharm, Pharmaceutics)
Lecturer
Madan Bhandari Academy of Health Sciences
Madan Bhandari Academy of Health Sciences

CONTENTS
• Particle size and distribution
• Average particle size
• Number and weight distribution
• Particle number
• Methods for determining particle volume
• Optical microscopy
• Sieving
• Sedimentation
• Measurement
• Particle shape
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• Specific surface
• Methods for determining surface area
• Permeability
• Adsorption
• Derived properties of powders
• Porosity
• Packing arrangement
• Densities.
• Bulkiness
• Flow properties
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OBJECTIVES

• Understanding the impact of particle sizes on pharmaceutical

processing / preparation.
• Learning of different methods used for characterization of
particles, particle size.
• Discussion of the characteristics and significance of surface area
and particle shape.
• Techniques utilized for determining the particle surface area.
• Derived properties of a powder.
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INTRODUCTION
• Is the science and technology of small particles.
• Also involves the study of the fundamental and derived
properties of the individual as well as collection of particles.
Fundamental properties Derived properties
Derived from

Individual particle Fundamental properties

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• The unit of particle size used in the micrometer

(µm), micron (µ) and equal to 10-6 m.
• As particle size decreases, the surface area
increases.
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Fundamental properties
• Particle size and size distribution
• Particle shape
• Particle surface area
• Particle weigh
• Particle number
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Derived properties
▪ Density of powders
▪ Flow properties of powders
▪ Porosity
▪ Bulkiness
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Importance of micromeritics in pharmacy

➢In pharmacy, knowledge and control of particle size and size
range is of paramount importance.
➢The size & hence the surface area of a particle can be related to
the physical, chemical & pharmacologic properties of drugs.
1. Release & dissolution:
• Particle size & surface area influence the release of a drug from a
dosage form. Higher surface area allows intimate contact of the
drug with the dissolution fluids in vivo & increases the drug
solubility & dissolution.
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2. Absorption & drug action:

• Particle size & surface area influence the drug absorption as well
as the therapeutic action. Higher the dissolution, faster the
absorption & hence quicker & greater the drug action.
3. Physical stability:
• The particle size in a formulation influences the physical stability
of the suspensions & emulsions. Smaller the size of the particle,
better the physical stability of the dosage form.
4. Dose uniformity:
• Good flow properties of granules & powders are important in the
manufacturing of tablets & capsules.
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Particle size

• Powder sample is characterized by particle shape, particle size and

particle size distribution.
• The size of a spherical particle can be easily expressed in terms of
its diameter.
• Size of the particles may be expressed as follows:
▪ Surface diameter, d : Diameter of a sphere having the same surface
s

area as that of the symmetric particle.

▪ Volume diameter, d : Diameter of a sphere having same volume as
v

that of the asymmetric particle.

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• Projected diameter, dp: Diameter of a sphere having the same area

of the asymmetric particle as observed under a microscope.
• Stoke’s diameter, dst: Diameter of an equivalent sphere undergoing
sedimentation at the same rate as the asymmetric particle.
• Sieve diameter, dsieve: Diameter of a sphere that passes through
the same sieve aperature as the asymmetric particle.
• Volume- surface diameter, dvs: Diameter of a sphere that has same
volume to surface area ratio as the asymmetric particle.
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Madan Bhandari Academy of Health Sciences

➢Particle size is denoted by micrometers.

➢One micrometer is equal to 10-3 mm or 10-6 m.
➢One millimicrometer is called one nanometer (nm).
One nanometer = 10-9 m or 10-6 mm or 10-3 µm.
1m = 1000 mm
1mm = 1000 µm
1µm = 1000 nm
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• If all particles have the same diameter then the powder sample is
called a monodisperse system, but if all particles are not of equal
size, then that sample is called polydispersed system
• Most pharmaceutical powders and dispersion are polydisperse
systems.
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Average particle size

• The particle size of a powder is analyzed microscopically and the

number of particles in each size range is determined.
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• From the above data the average particle size of the powder may
be calculated as
Particle size = Ʃnd /Ʃn
= 377/174
= 2.16 µm
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Dimensions of Particles in Pharmaceutical Dispersed

System
Particle size, Diameter Approximate Examples
sieve size
Micrometers Millimeter
(µm)
0.5-1.0 0.0005-0.010 - Emulsions, suspensions

10-50 0.010-0.050 - Upper limit of sub sieve range coarse

emulsion particles, flocculated suspension
particles
50-100 0.050-0.100 325-140 Lower limit of sieve range, fine powder
range
150-1000 0.150-1.000 100-18 Coarse powder range

1000-3360 1.000-3.360 18-6 Average granule size

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Particle size distribution

A collection of particles having mixture of varying size and shape,
the number of particle of same size range present in a sample is
known as size distribution.
The particle size distribution in a powder may be quantified by:
▪ Determining the number of particles present in each size range
▪ Determining the weight of particles present in each size rang.
When this number/ weight of particles lying within a certain size
range is plotted against size range or mean particle size, frequency
distribution curve is obtained.
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Determining number of particles present in each size range

❖Number of particle in different size range is calculated using
microscope.
Determining weight of particles present in each size range
❖Sieving method is used to determine the weight of the particle
present in each size range.
❖Sieves are arrange according to the descending order of their pore
size in this method.
❖Sieve is shake or agitate for sufficient period of time.
❖Particles settle in the sieve according to their particle size.
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• Particles retain on each sieve is collected and weight of particles

are obtained according to their size.
➢Number frequency distribution cure: Number of particles vs.
mean particle size
➢Weight frequency distribution curve: Weight of particles vs.
mean particle size
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• Two sample of powder may have the same average diameter but
may not have the same frequency distribution.
• So, expression of the size in terms of average diameter may not
give a clear expression of the particle size distribution.
• From frequency distribution curve
▪ Particle size distribution
▪ The particle size which occur most frequently
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Particle size may be expressed in two

ways
1. Monodisperse particle size:
▪ Its characteristics can be described by a
single diameter or equivalent diameter.
2. Polydisperse particle size:
▪ Common encounter in pharmaceutical
powder.
A polydispersed powder system is said to
have a normal distribution if a typical
bell shaped frequency distribution curve
is obtained. Fig: Normal size frequency
distribution curve
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➢However, normal distribution is not common in pharmaceutical

powder which are commonly processed by milling or
precipitation.
➢More commonly asymmetric or skewed distribution is obtained.
➢A frequency curve with an elongated tail towards higher size
ranges is positively skewed; the reverse case exhibits negative
skewness.
➢In some size distribution more than one mode occurs shows
bimodal frequency distribution.
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Madan Bhandari Academy of Health Sciences

Particle size determination methods

• There are various methods used to estimate particle sizes are:

▪ Optical microscopy
▪ Electron microscopy
▪ Sieving method
▪ Sedimentation method
▪ Coulter counter method
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OPTICAL MICROSCOPY
• Particle size in the range of 0.2 - 100µm can be measured.
• This method provides number distribution which can be converted
to weight distribution.
• Optical microscope lens has limited resolving power.
• Advanced microscopes have better resolving power and can
measure size in nano range: Ultramicroscope, Electron
microscope- Scanning Electron microscope (SEM), Transmission
Electron microscope (TEM).
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Procedure
• Eye piece of the microscope is fitted with a
micrometer.
• This eye-piece micrometer is calibrated using a
standard stage micrometer.
• The powder sample is dispersed in a suitable
vehicle in which it does not dissolve and its
properties are not altered.
• This sample is then mounted on a slide and
placed on the stage under the objective of
microscope.
• Around 300-500 particles are visualized. Their
diameter is noted and mean is computed.
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Calibrated using a standard stage micrometer

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Advantages
• Provides a direct visual representation of the particles.
• Any aggregates detected.
• Contamination of particles detected.
• Use of cover slip for arresting motion of particles
• Easy and simple.
• Requires an extremely small amount of sample.
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Disadvantages

▪ Length and breadth can be detected but depth or thickness of

particles cannot be measured.
▪ Slow and time consuming, tedious, inaccurate number of particles
to be measured is more.
▪ Large sample required.
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SIEVING

• Particle size in the range of 30-5000µm can be measured.

• It is an ordinary and simple method.
• Widely used as a method for the particle size analysis.
• Usually carried out using dry powders.
• Uses nests of standard sieves stacked one over the other.
• The particles on each sieve sizes are collected and weighed.
• Useful for coarse particles.
• Used to determine sieve diameter.
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• It find application in dosage form development of tablets and

capsules.
• Normally, 15% of fine powder should be present in granulated
material to get proper flow of material and achieve good
compaction.
• Thus percent of coarse, moderate, fine powder is estimated by
this method.
• Sieve analysis utilizes a wire mesh made of brass, bronze or
stainless steel with known aperture diameter which form a
physical barrier to particles.
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Method of sieving

1. Mechanical dry sieving method

a. Agitation method (Oscillation, Vibration, Gyration)
b. Brushing method
c. Centrifugal method
2. Wet sieving method
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Table: Opening of standard sieves, U.S series

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Madan Bhandari Academy of Health Sciences

In determining particle size by this method

• A nest of sieves with the coarsest on top is placed

on the shaker, a
powder sample of known weight is placed on the top of the sieve
shaken for a definite period of time.
• The powder passes through sieve and retain on that sieve
depending upon their size.
• The data obtained is analyzed and particle size as well as size
distribution is calculated.
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Disadvantages

• Aggregation: Due to electrostatic charge or moisture actual size is

not determined.
• Attrition: Size reduction
• Sieve shaking and duration of mechanical shaking can influence
the results.
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SEDIMENTATION METHOD

• Particle size can be determined by examining the powder as it

sediments out.
• Sample preparation: Powder is dispersed in a suitable solvent.
• If the powder is hydrophobic, it may be necessary to add
dispersing agent to aid wetting of the powder.
• In case where the powder is soluble in water it will be necessary to
use non-aqueous liquids or carry out the analysis in a gas.
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Principle of Measurement

• Particle size analysis by sedimentation method can be divided into

two main categories according to the method of measurement used.
• One of the type is based on measurement of particle in a retention
zone.
• Another type uses a non-retention measurement zone.
• An example of a non-retention zone measurement is known as the
pipette method.
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Andreasen pipette method

oOne of the most popular of the pipette methods was that developed
by Andreasen and Lunberg and commonly called the Andreasen
pipette.
oThe diameter is expressed as Stoke’s diameter, d - describes the
st

diameter of an equivalent sphere having the same rate of

sedimentation as that of the asymmetric particle.
Where,
h= distance of fall in time t
ρs= density of particle
ρo = density of dispersion medium
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Construction

• Consist of fixed-position pipette with 200

mm graduated cylinder (550mL) which
can hold about 500 mL of suspension
fluid.
• Pipette is located centrally in the cylinder
and is held in position by a ground glass
stopper so that its tip coincides with the
zero level.
• Three way tap allows fluid to be drawn
into 10 mL reservoir which can then be
emptied into a beaker or centrifuge tube.
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Method
▪ 2% suspension of powder is prepared in a suitable medium.
▪ For uniform distribution of drug deflocculating agent may be
added
▪ The suspension is transfer into the andreasen vessel.
▪ Place the stopper and shake the vessel to distribute the suspension
uniformly.
▪ Remove the stopper and place the two-way pipette and securely
suspend the vessel in a constant temperature water bath,
▪ At different time intervals. 10mL samples are withdrawn using
two- way stopcock and collected in watch glass.
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▪ Samples are evaporated and weighed.

▪ The weight or the amount of particles
obtained in each time interval is referred to
as weight undersize.
▪ The weights are converted into cumulative
weight undersize.
▪ Particle diameter is calculated from stoke’s
law, with ‘h’ in equation being height of the
liquid above the lower end of the pipette at
the time of withdrawing the samples.
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Advantages
• Can obtain precise result.
• Apparatus is inexpensive and the technique is simple.

Disadvantages
• Labarious method.
• Very small particles cannot be measured accurately due to prolong
settling rate
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Method for particle volume measurement

Conductivity method /Coulter counter method
• Used for measuring particle volume which is converted in
diameter.
• Particles ranging from 0.5-400µm can be measured by this method
and gives number distribution.
• The size expressed as volume diameter (dv)
Principle:
• When a particle suspended in a conducting liquid passes through a
small orifice (opening), on either side of which are electrodes, a
change in electric resistance occurs.
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• To form a very dilute suspension, powder samples are dispersed in

the electrolyte.
• A known volume of the suspension is pumped through the orifice
so that only one particle passes at a time through the orifice.
• If the suspension is sufficiently dilute, the particles pass through
the orifice one at a time.
• A constant voltage is applied across the electrodes so as to produce
a current.
• As the particle travels through the orifice, it displaces its own
volume of electrolyte and this results in an increased resistance
between the two electrodes.
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PROCEDURE
• It consists of two electrodes one of which is immersed into a beaker
containing the particle suspension in an electrolyte (NaCl).
• Other electrode is immersed into the electrolyte contained in a glass
tube and this tube is immersed into the beaker containing the
particle suspension in the electrolyte.
• This dispersion is filled in the sample cell which has an orifice and
maintains contact with the external medium.
• A known volume of suspension is passed through the orifice so that
only one passes at a time.
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• A constant voltage is applied across the electrodes so as to produce

current.
• When a suspended particle travels through orifice, it displaces its
own volume of electrolyte into the beaker.
• The change in electrical resistance is proportional to the volume of
the particles converted into a voltage pulse that is amplified and
processed electronically.
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Madan Bhandari Academy of Health Sciences

Advantages
• It is one of the precise and accurate method.
• Wide range of measurement particle diameter from approximately
0.5-400µm.

Disadvantages:
❑Aggregation of particle produce wrong result.
❑Coarse particles blocking a small diameter orifice.
❑Medium must be an electrolyte and low particle concentration.
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Particle shape
• Geometric shape and surface irregularity.
• It influence the surface area, flow of particles, packing and
compaction properties of the particles.
• Surface area per unit weight and unit volume are important in the
studies of absorption and dissolution.
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Particle number
• Defined as number of particles per unit weight.
• Suppose that the particles in powder are spherical then the volume
of a single particle is πdvn3/6 and mass will be (πdvn3ρ)/6g per
particle.
• The number of particles per gram can be obtained as
N=6/ πdvn3ρ
Where,
dvn = mean diameter based on volume and number
ρ= density of particle
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Specific surface area

• Specific surface of a powder is defined as the surface area per unit

volume (Sv) or surface area per unit weight (Sw).
• It may be derived from the following equation:
▪ Asymmetric particles-
Surface area per unit volume
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Surface area per unit weight

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Spherical particles-
Surface area per unit volume
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Method for determining surface area

• Surface area can be determined by one of the following two methods:

a. Adsorption method
b. Air permeability method
ADSORPTION THEORY:
• The amount of gas or solute adsorbed on the sample of powder is
found out and the surface area of the powder is determined
a. By using a solute which form a monolayer
b. By using adsorption of gas on powder
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By using a solute which form a monolayer

• This method involve the adsorption of solute from its solution on the
surface of powder whose area is to be determined.
• Firstly a solution of suitable solute is prepared in powder insoluble
medium.
• A known amount of powder is added in solution.
• After equilibrium the powder is filtered and remaining solute is
determined.
• Difference between quantity added and remaining gives the amount
adsorbed.
• If X g of solute adsorbed.
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• 1g mole of material contain avogedro’s number 6.0223 × 1023

number of molecules.
• Then total number of molecules will be
X × 6.0223 × 1023
❖Surface area of 1 molecule of solute is known and surface area of
powder can be calculated.
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By using adsorption of gas on powder

• Quantosorb is an instrument used for determination of surface area
by gas adsorption method.
• The powder whose surface area is to be determined is introduced
into a cell.
• Nitrogen is used as adsorbed gas and helium is an inert gas and
passed through the powder in the cell.
• A thermal conductivity detector measures the amount of nitrogen
adsorbed at every equilibrium pressure.
• A bell shaped curve is obtained on a strip chart recorder.
• The single height gives the rate of adsorption of nitrogen gas.
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• The area under curve gives the amount of gas adsorbed on the
powder sample.
• The volume of nitrogen gas [(cm3)] adsorbed by 1 g of powder is
given by BET equation:
P/ V (P0 – P) = 1/ Vmb + (b-1)P/ Vmb P0
Where,
V = Volume of gas in cm3 adsorbed per g of powder at pressure (p)
P0 = Saturated vapor pressure of liquid nitrogen at the temperature
b = Constant
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The given equation is used for determining the specific surface area
of the powder:
Sw = AmN / m/ρ × Vm
Where,
m/ρ = Molar volume of the gas which is equal to 22,414 cm3/ mole
at N.T.P
N = Avogadro’s number
Am = Area of a single close packed gas molecule absorbed as a
monolayer on the surface of the powder particles. For nitrogen the
value is 16.2 × 10-16 cm2.
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AIR PERMEABILITY METHOD

• It is based on the principle that the resistance offered to the flow of air
through the compact powder is proportional to the surface area of the
powder.
• The greater the surface area per gram of the powder, the greater is the
resistance to flow.
• When the air is allowed to pass through the plug of powder resistance
to the flow of air occurs.
• This resistance is related to the surface area of the powder.
• The specific surface (Sw) can be calculated by Kozeny – Carman
equation is used to estimate the surface area by this method.
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Where,
A = cross sectional area of the bed (pack), cm2
∆P = pressure difference of the plug
t = time of flow, seconds
l = length of the sample holder, cm
Ɛ = porosity of the powder
Sw = surface area per gram of the powder, cm2/g
ղ = viscosity of the air, (poise)
K = a constant (5.0 ±0.5) that accounts the irregular capillaries
V = volume of air flowing through the bed, cm3
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METHOD
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DERIVED PROPERTIES OF POWDER

• A part from fundamental properties, there are derived properties
which are based on fundamental properties.
• These are as follows:
1. Porosity
2. Packing arrangement
3. Densities
▪ Bulk density
▪ Tap density
▪ Granular density
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4. Particle volume
▪ Bulk volume
▪ Tap volume
▪ Void volume
5. Bulkiness
6. Angle of repose
7. Compaction
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POROSITY

• Porosity is defined as the number of small spaces or voids

present within a solid material.
• It is a measure of the void spaces in a material and is a fraction of
the volume of voids over the total volume (bulk volume),
between 0 and 1, or as a percentage between 0-100%
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• Porosity is expressed as percentage

Ɛ = Vb – Vp
V b

• In a non –porous material, the bulk volume is equal to the true

volume.
• Most of the solids are porous i.e., they have internal pores, hence
the volume is greater than the true volume.
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• The volume of space is known as the void volume given by:

V = Vb – Vp
Where,
Vb = bulk volume
Vp = True volume
V = Void volume
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Intraparticular porosity

➢It means space within a single layer particle.

% Ɛ = (1-ρg / ρ) ×100
Where,
ρg = Granular density
ρ = True density
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Interparticular porosity

• It means space between two or more than two particles.

% Ɛ = (1-ρb / ρ) ×100
Where,
ρb = Bulk density
ρ = True density
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EXAMPLE
• A sample of calcium oxide powder with a true density of 3.203
and weighing 131.3g was found to have a bulk volume of 82cm3
when placed in a 100 mL graduated cylinder. Calculate the
porosity?
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Packing arrangement in powder bed

• When the particles are of uniform size of spheres, they can be
packed by any one packing arrangement
1. Closest or rhombohedral packing
2. Most open, looset or cubic packing

Closest packing
Loosest packing
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❑The total volume occupied by the particles is affected by its

arrangement in a powder ----- affects the bulk density and porosity
of the powder.
❑Particles in a powder are neither spherical nor uniform in size, any
type of packing between these ideal solutions is possible.
• If the porosities of spherical particles of a powder are about 26%, it
represents a closed packing arrangement.
• If the porosities of spherical particles of a powder are about 48%, it
represents a loose packing arrangement.
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• Generally, the porosities of powder lie between 30-50%.

• If the particles differ in size distribution extensively, the porosities
are below 30. The small particles accommodate the voids between
large particles.
• If aggregated and flocculated particles are present in a powder, the
porosities are above 50%.
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The packing arrangement in a powder

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DENSITY

• Density is defined as weight per unit volume (W/V).

Types of densities:
▪ There are 3 types of densities:
❖True density
❖Bulk density
❖Granular density
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True density (ρ)

• It is the density of the actual solid material.
• It is defined as ratio of the given mass of a powder to true volume.
True volume = Bulk volume – void volume
True density = weight of the powder / true volume of powder
➢ Can also be defined as the density of the sample which excludes
the volume of the pores and voids within the sample (intra-
particular).
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Measurement of true density

• Gas displacement method
• Liquid displacement method

Gas (Helium or Nitrogen) Displacement method:

• Helium gas can penetrate the smallest pores and clefts between the
particles due to its smaller size.
• The method is more preferable for obtaining precise values close
to its true density.
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Helium pycnometer includes the following components:

i) Sample Cell or Holder (A):
• Sample cell present at the left side of the helium pycnometer is
sealed after sample loading.
ii) Valve (B):
• It is attached to the sample holder and is used to discharge air from it
and introduce helium gas in the apparatus.
iii) Pressure Detector (C):
• Used to maintain constant pressure.
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iv. Piston (D):

• Included in order to read the corresponding pressures, which are
also associated with the powder volume.

Helium pycnometer
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Method

• Volume of empty pycnometer is determined.

• Air present in the sample holder is removed by applying vacuum
and helium gas is introduced into the instrument through the valve.
• Using the movable piston, the pressure is adjusted at a particular
value.
• At this point, the scale reading is symbolized by U1 signifying the
empty cell volume.
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• The pycnometer is calibrated by loading the sample holder with a

standard sample (stainless steel spheres) of known true volume
(Vc).
• Sample holder is then sealed and air is removed.
• Same concentration of helium gas is introduced into the apparatus.
• Pressure is adjusted to pre – set the value with the help of movable
piston.
• Reading on the scale is represented by U2 at this point.
• The total volume occupied by the sphere can be calculated by
subtracting the value of U1 from U2.
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i.e., Volume occupied by the sphere = U1 – U2

• Last step is used for calculating the sample volume.
• The stainless steel spheres are replaced with the test sample
powder.
• Air is removed and same amount of helium gas is introduced in the
pycnometer.
• Pressure is adjusted with the help of movable piston.
• At this point, the reading on the scale is denoted by Us.
• The difference between U1 and Us denotes the volume occupied
by the sample.
•
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i.e., volume occupied by the sample = U1 –Us

The working mechanism of the apparatus is based on following
equation:

Where,
Vt = True volume of the sample
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Liquid displacement method:

• Used for determining the true density of non –porous powders by

using pycnometer or graduated cylinder.
• A solvent in which the powder is insoluble is selected.
• Values obtained in this method are comparatively lower than those
obtained in helium displacement method.
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Method

Pycnometer or specific gravity bottle may be used.

Weight of pycnometer = W1
Weight of pycnometer + sample (or glass beads) =W2
Weight of sample = W3 = W2 - W1
Weight of pycnometer with powder and filled with solvent = W4
Weight of the liquid displaced by solids = W4 –W2
True density = W2 – W1 / W4 – W2
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Granule density (ρg)

• May be determined by the displacement of mercury which fails to

penetrate the internal pores of the particles at ordinary pressures.
• Granule density is the ratio of the granule weight to the granule
volume and can be expressed as:
Granule density = Granule weight / Granule volume
• Granule volume is the mercury weight displaced by the granules in
pycnometer.
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Bulk density (ρb)

▪ It is the ratio of the mass of the powder and its bulk volume.
▪ Includes the volume of all the pores within the sample.
▪ For determination of bulk density- a weighed quantity of powder
introduced in graduated measuring cylinder tapped mechanically
either manually till a constant volume is obtained.
Madan Bhandari Academy of Health Sciences

Tapped density (ρT)

• It is the ratio powder to tapped volume.

Madan Bhandari Academy of Health Sciences

During tapping, particles

gradually pack more
efficiently, the powder
volume decreases and the
tapped density increases.

Tap densitometer
Madan Bhandari Academy of Health Sciences

Bulkiness
➢Specific bulk volume
➢The reciprocal of bulk density.
➢Important consideration in the packaging of powders.
➢Bulkiness increases with the decrease in a particle size.
➢In mixture of materials of different sizes, the smaller particles
shift between the larger ones and tend to reduce bulkiness.
➢The bulk density of calcium carbonate vary from 0.1 to 1.3 and
the lightest (bulkiest) type require a container about 13 times
larger than that needed for the heaviest variety.
Madan Bhandari Academy of Health Sciences

Application

• It is a useful property to be considered while choosing a suitable

container for packaging or during filling of drug powders into
capsules.
Madan Bhandari Academy of Health Sciences

Flow properties of powders

• Powders may be free- flowing or cohesive (“sticky”).

• Important parameter to be considered in the production of
pharmaceutical dosage forms.
• Example:
✓Dies filling during tableting
✓Capsules filling
Directly depend on the flow properties of the powder.
Madan Bhandari Academy of Health Sciences

Flow properties of powders depends on

i. Cohesiveness or stickiness between particles due to presence of
Van der Waals, surface tension and electrostatic forces.
• Cohesiveness of particles has been found to depend upon a number
of factors.
a. Particle size and shape
✓Very fine particles tend to be more cohesive due to their large
surface area.
b. Density or porosity of the powders
✓Dense materials tend to be less cohesive than lighter ones
Madan Bhandari Academy of Health Sciences

c. The presence of adsorbed materials on the powder surface

✓Moisture increase cohesiveness of particles
ii. Adhesion between the particles and the container wall due to the
above forces.
iii. Friction between particles due to surface roughness.
iv. Physical interlocking of particles specially if these are of
irregular shape.
Madan Bhandari Academy of Health Sciences

Many common manufacturing problems are

attributed to powder flow:
• Uneven powder flow
➢Excess entrapped air within powders- capping and lamination
➢Increase particle’s friction with die wall causing lubrication
problems and
➢Increase dust contamination risks during powder transfer.
➢Non- uniformity of dose
oNon-uniformity (segregation) in blending
Madan Bhandari Academy of Health Sciences

• Powder transfer through large equipment such as hopper.

• Powder storage – Which for example result in caking tendencies
within a vial or bag after shipping or storage time.
• Separation of small quantity of the powder from the bulk –
specifically just before the creation of individual doses such as
during tableting, encapsulation and vial filling which affect the
weight uniformity of the dose.
Madan Bhandari Academy of Health Sciences
Madan Bhandari Academy of Health Sciences

Powder flow problems

Madan Bhandari Academy of Health Sciences

TEST TO EVALUATE THE FLOWABILITY OF A

POWDER

1. Carr’s compressibility index

2. Hausner’s ratio
3. Angle of repose
Madan Bhandari Academy of Health Sciences

1. Carr’s compressibility index

A volume of powder is filled into a graduated glass cylinder and

repeatedly tapped for a known duration. The volume of powder after
tapping is measured.
• Carr’s index (%) =
Tapped density – Poured or bulk density ×100
Tapped density
• Bulk density = weight / bulk volume
• Tapped density = weight / true volume
Madan Bhandari Academy of Health Sciences

Relationship between powder flowability and %

compressibility
Consolidation index (Carr, %) Flow properties
5-15 Excellent
12-16 Good
18-21 Fair to passable
23-35 Poor
33-38 Very poor
>40 Extremely poor
Madan Bhandari Academy of Health Sciences

2. Hausner ratio:
Hausner ratio =Tapped density / Poured or bulk density

Hausner ratio is related to interparticle friction:

• Value less than 1.25 indicates good flow.
The powder with low interparticle friction, such as coarse spheres.
• Value greater than 1.5 indicates poor flow.
more cohesive, less free-flowing powders such as flakes.
• Between 1.25 and 1.5, added glidant normally improves flow.
• > 1.5 added glidant doesn’t improve flow.
Madan Bhandari Academy of Health Sciences

Hausner ratio Flow Porperties

1.00-1.11 Excellent
1.12-1.18 Good / free flow
1.19-1.25 Fair
1.26-1.34 Passable
1.35-1.45 Poor
1.46-1.59 Very poor
>1.60 Non - flow
Madan Bhandari Academy of Health Sciences

ANGLE OF REPOSE (θ)

• When a powder is poured onto a surface, a pile is formed. One of the simplest
indicators of the flow properties is the angle of repose, which is formed
between the free surface of the powder and the horizontal surface.
• Mathematically,
tanθ = h/r
Where,
• h= height of pile
• r = radius of pile
• θ =angle of repose
Madan Bhandari Academy of Health Sciences

• Angle of repose is a function of the surface roughness.

• Rougher and more irregular the surface of particles, the more the
angle of repose.
• As the particle become less and less spherical, the angle of repose
increases while the bulk density and flowability decreases.
• Powder with low angle of repose will flow freely and powders
with the high angles of repose will flow poorly.
Madan Bhandari Academy of Health Sciences

Repose angle (o) Flow properties

25-30 Excellent
31-35 Good
36-40 Fair
41-45 Passable
46-55 Poor
56-65 Very poor
>66 Very very poor
Madan Bhandari Academy of Health Sciences

DIFFERENT METHODS OF DETERMINING ANGLE OF

REPOSE
1. Static angle of repose (Funnel method)
• Allow the material to flow through a funnel or orifice onto a
horizontal surface below.
• The angle of conical heap so formed can be determined from
simple geometry.
Madan Bhandari Academy of Health Sciences

2. Dynamic angle of repose: (Tilting box method and

rotating cylinder method)
a. Tilting box method:
• A sand paper lined rectangular box is fixed with the powder
and carefully tilted until the contents begin to slide.
• The repose angle is the angle formed by surface of the box
with the horizontal plane.
Madan Bhandari Academy of Health Sciences
Madan Bhandari Academy of Health Sciences

b. Rotating cylinder method

• A hollow cylinder half- filled with the test powder with

one sealed by transparent plate.
• Rotate it on horizontal plane, until the powder surface
levels.
• The curved wall is lined with sand paper to prevent
slippage.
• The angle formed by surface levels with the horizontal
plane is the repose angle.
Madan Bhandari Academy of Health Sciences
Madan Bhandari Academy of Health Sciences

3. Drained angle of repose

a. Ledge method:
• A rectangular vessel (ledge), which contains a movable or sliding
shutter at the bottom side.
• A vessel is filled with the sample to be tested.
• Then the shutter is opened to allow the drainage of material itself.
• The angle formed by material left in the ledge with horizontal
plane is known as drained angle of repose.
Madan Bhandari Academy of Health Sciences
Madan Bhandari Academy of Health Sciences

b. Crater method
• A cubic vessel, which contains a movable or sliding shutter at the
center of the bottom.
• A vessel is filled with the sample to be tested.
• Then the shutter is opened to allow the drainage of material itself.
• The angle formed by material left in the cubic vessel with
horizontal plane is known as drained angle of repose.
Madan Bhandari Academy of Health Sciences

c. Platform method

• A large container with built-in-platform is used.

• The bottom of the container is provided with a sliding shutter.
• The container is filled with the sample to be tested.
• Then the shutter is opened and the material is allow to flow out at the
bottom, leaving an undisturbed conical heap on the platform.
Madan Bhandari Academy of Health Sciences

FACTORS AFFECTING FLOW PROPERTY OF A POWDER

Particle’s size and distribution

Particle shape and texture

Surface forces

Flow activators
Madan Bhandari Academy of Health Sciences

Alternation of particle’s size and distribution

• Flow ability of powder is optimum in certain particle size.

• Coarse particles are more preferred compared to fine ones as they
are less cohesive.
• Size distribution can also be altered to improve flowability by
removing a proportion of the fine particle fraction or by increasing
the proportion of coarse particles, such as occurs in granulation.
Madan Bhandari Academy of Health Sciences

Alternation of particle shape and texture

• Particle shape : Spherical particles have better flow properties than

more irregular particles.
• Spherical particles are obtained by spray drying or by temperature
cycling crystallization.
• Particle’s texture: Particles with very rough surfaces will be more
cohesive and have a greater tendency to interlock than smooth
surfaced particles.
Madan Bhandari Academy of Health Sciences

Alteration of surface forces

• Reduction of electrostatic charges can improve powder flowability.
Electrostatic charges can be reduced by altering process conditions
to reduce frictional contacts.
• Moisture content of particle affects powder’s flowability.
• Adsorbed surface moisture films tend to increase bulk density and
reduce porosity.
• Drying the particles will reduce the cohesiveness and improve the
flow.
• Hygroscopic powders, stored and processes under low humidity
conditions.
Madan Bhandari Academy of Health Sciences

Formulation additives (flow activators)

• Flow activators are commonly referred as glidants.

• Improves the flowability of powders by reducing adhesion and
cohesion.
• E.g., talc, Maize starch and magnesium stearate

n-gl.com