Micromeritics

Wondesen G.
Outline

Micromeritics

Particle size and size distribution

Methods for determination of particle size and size

distribution
 Particle shape and surface area

Methods for determination of surface area

Derived properties of powders

densities, porosity, packing arrangement,

flowability
Objective
o After completion of this chapter, the student will be able to

 Describe the concept of particle size as it applies to

pharmaceutical sciences.
 Discuss the common particle size of pharmaceutical preparation

and their impact on pharmaceutical processing/preparation.

 Discuss the method of determining particle size.

 Discuss the role and importance of particle shape and surface

area.
 Understand the methods for determining particle surface area.

 State the two fundamental properties for any collection of

particles.
 Describe derived properties of a powder and their importance.
Micromeritics
Definition: It is the science and technology of
small particles.
It is the study of a number of characteristics, including
particle size and size distribution, shape, angle of
repose, porosity, apparent density, and bulkiness.
The unit of particle size used is the micrometer,( μm),
micron, (μ), and equal to 10-6 m.
As particle size decreases, the specific surface
area increases
The knowledge & control of the size of particles is of
importance in pharmacy and materials science.
The particle size & the surface area can be related in a
significant way to
 the physical
 chemical
 pharmacologic properties of drugs.
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
 Absorption & drug action
Particle size & surface area influence the drug
absorption & subsequently the therapeutic action.
 Higher the dissolution, faster the absorption & hence
quicker & greater the drug action.
 Physical stability
The particle size in a formulation influences the
physical stability of the suspensions & emulsions.
 Dose uniformity
In tablet and capsule manufacture, control of the particle
size is essential
in achieving the necessary flow properties and proper
mixing of granules and powders.
Particle Size and Size Distribution

Particle size is a basic property of a powder, which is

essential to powder technology and dosage form design.

Particles with different size and size distributions exhibit

different behaviours.
For instance, smaller particles have greater specific

surface area and their bulk density, porosity, flowability,

and solubility significantly differ from that of larger
particle
Fundamental properties of collection of particles

In a collection of particles of more than one size

( polydisperse), two properties are important, namely

 Particle size and size distributions

 the shape and surface area of the individual

particles
The size of a sphere is readily expressed in terms of its
diameter.
As the degree of asymmetry of particles increases,
however, so does the difficulty of expressing size in terms
of a meaningful diameter.
Under these conditions, there is no one unique diameter
for a particle.
 Recourse must be made to the use of an equivalent
spherical diameter, which relates the size of the particle to
the diameter of a sphere having the same surface area,
volume, or diameter
the surface diameter, ds, is the diameter of a sphere
having the same surface area as the particle in
question.
The volume diameter, dv, the diameter of a sphere
having the same volume as the particle
 the projected diameter, dp, is the diameter of a sphere
having the same observed area as the particle when
viewed normal to its most stable plane.
The Stokes diameter, dst, which describes an
equivalent sphere undergoing sedimentation at the
same rate as the asymmetric particle
Usually , the type of diameter used reflects the method
employed to obtain the diameter
 the projected diameter is obtained by microscopic
techniques
 the Stokes diameter is determined from sedimentation
studies on the suspended particles.
Asymmetric particle

Different Equivalent Spheres

11
Average Particle Size

Any collection of particles is usually polydisperse.

therefore necessary to know how many particles of the

same size exist in the sample.

Thus, we need an estimate of the size range present

and the number or weight fraction of each particle size,

i e. the particle-size distribution
 From it we can calculate an average particle size for

the sample.
general equation for the average particle size, whether it be
an arithmetic, a geometric, or a harmonic mean diameter

Where n -is the number of particles in a size range whose

midpoint, d,
p is an index related to the size of an individual particle,
because d raised to the power p = 1, p = 2, or p = 3 is an
expression of the particle length, surface, or volume,
respectively
p (p is positive mean is arithmetic), (p is zero), geometric
or(p is negative) harmonic
f the frequency index,, has values of 0, 1, 2, or 3, then the
size frequency distribution is expressed in terms of the total
number, length, surface, or volume of the particles,
respectively.
Statistical Diameters
Average particle size
The particle size of a powder is analyzed
microscopically and the number of particles in
each
Size rangesize
(µm) range is determined
Mean size No particle in nd
range each size range
(in µm ) (d) (n)
0.5-1.0 0.75 4 3
1.0-1.5 1.25 18 22.5
1.5-2.0 1.75 39 68.25
2.0-2.5 2.25 73 164.25
2.5-3.0 2.75 24 66
3.0-3.5 3.25 14 45.5
3.5-4.0 3.75 2 7.5
n=174 nd=377

16 Average Particle size = 377/174

Calculation of Statistical Diameters from Data Obtained by Use of
the Microscopic Method (Normal Distribution)
Particle-Size Distribution
Particle size distribution refers to the
percentage of the particles within a certain
size range.
it is important for understanding powder
uniformity
 it has a great impact on the drug
dissolution profile
It can be expressed as the frequency
distribution and the cumulative frequency
distribution
number distribution, implying that they
were collected by a counting technique
such as microscopy.
 The particle size distribution in a
powder may be quantified by:
1. determining the number of particles
present in each size range
2. determining the weight of particles
present in each size range.
 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
19
 number frequency distribution curve
20 FIGURE . A frequency distribution plot.
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

(mode)
21
A poly dispersed powder
system is said to have a
normal distribution if a
typical bell shaped frequency
distribution curve is obtained
 The distribution is symmetric

% frequency
around the mean, which is
also the mode.
 However, normal distribution
is not common in
pharmaceutical powder
Particle size
 which are frequently Fig. normal or
processed by milling or Gaussian size
precipitation frequency distribution
22 curve
But, most powder particles will not
exhibit a normal distribution
 Their curves are usually skewed to
one side depending on which size
range occupies a larger portion of the
powder solids
 the smaller particles
 the larger particles.
Positively skewed
 A frequency curve with an elongated
tail towards higher size ranges
23
Negative skewed:
a positively skewed size negatively skewed size
distribution distribution;
positively or a
negatively skewed
distribution can be
transformed into a log
normal distribution

% frequency
 by replotting the x-axis

with the logarithmic

value of the diameter. Log particle size

log-normal Fig. log normal distribution curve

distribution obtained for a polydisperse
powder
curve
25
Alternatively, a particle size distribution can be obtained

by sequentially adding the percent frequency values to

produce a cumulative percent frequency distribution
 cumulative percent frequency undersize

 It is the values obtained when the addition sequence

begins with the finest particles,

 cumulative percent frequency oversize

 The reverse case

26
ble 2 Cumulative frequency distribution data

27
plot of

Cumulative % frequency undersize

cumulative percent
frequency vs
particle size
• gives sigmoid
curve with the
mode being the
Particle size (μm)

28
particle size of
Cumulative % frequency under size (probability scale)
When the log of the
particle size is plotted
against the cumulative
% frequency on
probability scale a linear
relationship is obtained.
 the log probability plot.

29 log Particle size (µm)

Types of Diameter
 particle size (diameter) can be described by
different expression
A mean particle diameter
the sum of all individual diameter
divided by the total number of
particles .
sensitive to extreme value
represent the size present in the greatest
number

30
Median diameter

a diameter for which 50% of the particles

are less the stated size.
Mode diameter

represent the particle size occurring most

frequently in the sample
Mean volume surface diameter

used to express powder particle size in

terms of surface area per unit volume.
3
 nd
 n2
31
dave =
Example 1
A) Present the size distribution from the
following data by histogram and
B) present the cumulative percent frequency
distribution (under and over size)
C) A mean particle diameter, Median
diameter, Mode diameter and Mean
volume surface diameter
Methods for Determining Particle
Size
 Many methods are available for determining particle size
 Microscopy,
 Sieving,
 Sedimentation, and
 the determination of particle volume (Coulter counter)
 None of the measurements are truly direct methods
 Although the microscope allows the observer to view the
actual particles, the results obtained are probably no more
“direct” than those resulting from other methods
 because only two of the three particle dimensions are
ordinarily seen.
 The sedimentation methods yield a particle size relative to
the rate at which particles settle through a suspending
medium
 a measurement important in the development of emulsions
and suspensions
A guide to the range of particle sizes applicable to each method is given in Figure

Fig. Approximate size ranges of methods

used for particle-size and specificsurface
Optical microscopy (range: 0.2 -100 um)
The microscope eyepiece is fitted with a micrometer by

which the size of the particles may be estimated.

 The effective size range for analyzing particles is about
0.2 to 100 µm.
Dilute suspension of the particles whose size are to be

determined is prepared in a liquid in which it is insoluble.

A drop of suspension is placed on the slide

The eyepiece of the microscope is fitted with micrometer

The particles observed are
counted
 for ease the field can be
projected or photographed
average diameter of a
particulate system is
obtained by measuring the
particles at random along a
given fixed line.
• At least 300- 500 particles
must be counted in order to
obtain a good size
distribution analysis of data.
The particles are measured along an arbitrarily chosen
fixed line, generally made horizontally across the
center of the particle.

Martin's diameter is the length of a line that bisects the

particle image
 The line can be drawn in any direction but must be in
the same direction for all particles measured.

 Feret's diameter, is the distance between two tangents

on opposite sides of the particle parallel to some fixed
direction, the y direction in the figure.

the projected area Diameter is the diameter of a circle

with the same area as that of the particle observed
perpendicular to the surface on which the particle
rests.
A general diagram providing definitions of the
Martin, Feret and projected diameters
 Advantages
 Providing a direct visual representation of the
particles
 Requires an extremely small amount of
sample
 Needs no calibration by other methods
 The equipment is relatively inexpensive to
acquire and maintain
 It can provide details about shape, crystal
habit, and homogeneity within the sample in
addition to size
 Agglomerate can be detected.
 Disadvantage
The measured diameter of the particles
represents two dimensions only.
Slow and tedious process.
 Sieving
Uses nests of standard
sieves stacked one over the
other.
Involves mechanical shaker.
The particles on each sieve
sizes are collected and
weighed.
Useful for coarse particles

(>50m)
if extreme care is used,
however, they can be
employed for screening
material as fine as 44 μm
(No. 325 sieve).
The nest of sieves is arranged from coarser mesh
opening to smaller mesh opening, top to bottom
the powder sample of known weight is placed on the
top of the sieve & shaken for a definite period of time.
The powder is classified as having passed through one
sieve and being retained on the adjacent finer sieve.
 Mass collected on each sieve is weighed

 Percentage of sample, collected on each sieve

 Cumulative percentage of sample retained on each

sieve
Advantage
 low-cost and
 ease of operation.
Disadvantage
 sieving errors can arise from a number of
variables including
 The shape of the particles
 Weight of sample loaded onto the sieve
 Duration and intensity vibration
 aggregation- due to electrostatic charge

caused by friction or moisture

 actual size is not determined
 Attrition of granular pharmaceutical
Sedimentation (range: 0.8 -300μm):
Andreasen pipette usually
consists of
 550 ml stoppered
cylindrical vessel with 5.5
cm internal diameter
 The stopper has an integral
10 ml bulb pipette
 Its lower tip should be 20
Andreasen apparatus
cm below the surface of for determining
the suspension particle size by the
gravity
But, centrifugal sedimentation
method.
sedimentation is used to
1 or 2% suspension of the powder is placed

in the vessel up to 550 ml mark.

Shaked for uniform distribution of the
particles within the medium
Left undisturbed in constant temperature

bath
10 ml sample is drawn at various time

interval
The samples are evaporated and weighed
The particle diameter corresponding to the various time
period is calculated using the Stocks equation
V= h = d2st(ρs – ρo)g
t 18ηo
 V is the rate of settling
 h the height of the liquid above the lower end of
the pipette at the time each sample is removed.
 dst is the mean diameter of the particles based on
the velocity of sedimentation
 ρs is the density of the particles
 ρo is the density of dispersion medium
 ηo is the viscosity of the medium
 g acceleration due to gravity
The equation holds exactly only for spheres falling freely
without hindrance and at a constant rate.
The residue or dried sample obtained
at a particular time is the weight
fraction having particles of size less
than the size obtained by the Stokes-
law calculation for that time period of
settling.
The weight of each sample residue is
the weight undersize and the sum of
the successive weights is the
cumulative weight undersize.
The cumulative weight undersize can then
be plotted on a probability scale against the
particle diameter on a log scale using a log-
Advantage

i. the apparatus is inexpensive and the technique is

simple
ii. The results obtained are precise provided the technique
is adequately standardized
Disadvantages

1. Method is laborious
2. Very small particles cannot be determined accurately
since their settling is unduly prolonged
3. The particles must not be aggregated or clumped together
in the suspension
4. the rate of sedimentation of a particle must not be so
rapid that turbulence is set up
 because this in turn will affect the sedimentation of
Example, Stokes Diameter
A sample of powdered zinc oxide, density 5.60

g/cm3 is allowed to settle under the acceleration

of gravity, 981 cm/sec2 at 25 C. The rate of
settling v is 7.30 x 10-3 cm/sec; the density of
the medium is 1.01 g/cm3, and its viscosity is 1
centipoise= 0.01 poise or 0.01 g/cm sec.
Calculate the Stokes diameter of the zinc oxide
Powder.

 Answer 5.4 x 10-4 cm or 5.4 m

Particle Volume
Measurement
(Coulter counter)
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
Schematic diagram of a
Coulter counter
o Powder samples are dispersed in the
electrolyte to form a very dilute suspension.
oA known volume of the suspension is
pumped through the orifice so that only one
particle passes at a time through the orifice
o A constant voltage is applied across the
electrodes so as to produce a current.
o As the particle travels through the orifice
it displaces its own volume of electrolyte
and
 this results in an increased resistance b/n
the two electrodes.
For Stokes's law to apply, a further
requirement is that
 the flow of dispersion medium around the
particle as it sediments is laminar or
streamline.
 i.e the rate of sedimentation of a particle
must not be so rapid that turbulence is set
up
 because this in turn will affect the
sedimentation of the particle.
Whether the flow is turbulent or laminar is
indicated by the dimensionless Reynolds
number, Re, which is defined as
According to Heywood, Stokes's law cannot
be used if Re is greater than 0.2
 because turbulence appears at this value.
 On this basis, the limiting particle size under
a given set of conditions can be calculated as
follows.
Rearranging equation and combining it with
equation gives

And thus
Example 1
Largest Particle Size
1. A powdered material, density 2.7 g/cm3, is suspended
in water at 20°C. What is the size of the largest particle
that will settle without causing turbulence? The
viscosity of water at 20°C is 0.01 poise, or g/cm sec,
and the density is 1.0 g/cm3.

Example 2
Particle Size, Setting, and Viscosity
2. If the material used in Example 1 is now suspended in
a syrup containing 60% by weight of sucrose, what will
be the critical diameter, that is, the maximum diameter
for which Re does not exceed 0.2? The viscosity of the
syrup is 0.567 poise, and the density is 1.3 g/cm3.
o The change in resistance is converted into a

voltage pulse which is amplified and

processed electronically.
o Pulses falling within precalibrated limits or

thresholds are used to split the particle size

distribution into many different size ranges.

Equivalent diameter
o Volume diameter, dv
Advantage
o The operation is very rapid (<30s)

o The result is reliable (4000 particle per

second ,large number of particles are counted)

o Operator variability is avoided

Disadvantage
o The material has to be suspended in an

electrolyte liquid
o Aggregation of particles can give false result.
2. Particle Shape and Surface Area

Knowledge of the shape and the surface

area of a particle is desirable.
The shape affects

the flow

packing properties of a powder

It also has some influence on the surface

area.
The surface area per unit weight or
volume is an important characteristic of a
Particle Shape
A sphere has minimum surface area
per unit volume
 The more asymmetric a particle, the
greater is the surface area per unit
volume
The surface area and volume of a
sphere:

and
o To obtain an estimate of the surface or volume of a
particle (or collection of particles) whose shape is not
spherical
 it is necessary to choose a diameter that is
characteristic of the particle and relate this to the
surface area or volume of sphere through a correction
factor.
o Suppose the particle size is determined
microscopically in terms of dp , then

o αs is the surface area factors and

o ds the equivalent surface diameter

o αv is the volume factor and

o dv is the equivalent volume diameter
Specific surface area
is the surface area per unit volume (Sv ) or per unit

weight (Sw) and can be derived as follows

 The surface area per unit weight (Sw) is therefore

Where ρ is true density of the particles

61
Particle shape and surface area…
Substituting for Sv

dvs is the volume-surface diameter

For spherical and nearly spherical

simplifies to because αs/αv = 6.0 for a

62
sphere.
Example 1
Determine the total surface of 5 g of an
antibiotic powder in which particle have
an average diameter dvs of 2 μm and a
true density of 2.4 g/cm3. assume that
the particles are spherical.
Example 2
What are the specific surfaces, Sw
and Sv, of particles assumed to be
spherical in which ρ = 3.0 g/cm3 and
dvs is 2.57 μm?.
Methods for Determining Surface Area
Two methods are commonly available that permit
direct calculation of surface area.
 In the first, the amount of a gas or liquid solute
that is adsorbed onto the sample of powder to
form a monolayer is a direct function of the
surface area of the sample.
 The second method depends on the fact that
the rate at which a gas or liquid permeates a bed
of powder is related to the surface area exposed
to the permeant
In practice, the flow rate through the plug, or
bed, is also affected by (a) the degree of
compression of the particles and
Adsorption Method
Particles with a large specific surface are good
adsorbents for the adsorption of gases and of
solutes from solution

In determining the surface of the adsorbent, the

volume in cubic centimeters of gas adsorbed per
gram of adsorbent can be plotted against the
pressure of the gas at constant temperature to give
a type II isothermas shown in Figure

The adsorbed layer is monomolecular at low

pressures and becomes multimolecular at higher
pressures.
 The completion of the monolayer of nitrogen on a
powder is shown as point B in Figure
Fig. Isotherm showing the volume of nitrogen
adsorbed on a powder at increasing pressure
ratio.
Point B represents the volume of adsorbed gas
The volume of nitrogen gas, Vm, in cm3 that 1 g of
the powder can adsorb when the monolayer is
complete is more accurately given by using the
Brunauer, Emmett, and Teller (BET) equation,
which can be written as

where V is the volume of gas in cm3 adsorbed per

gram of powder at pressure p,
 p0 is the saturation pressure of liquefied nitrogen at
the temperature of the experiment, and
b is a constant that expresses the d/f b/n the heat of
adsorption and heat of liquefaction of the adsorbate
(nitrogen).
Fig. 18-11. A linear plot of the Brunauer,
Emmett, and Teller (BET) equation for the
adsorption of nitrogen on a powder
Air Permeability Method
The principal resistance to the flow of a fluid
such as air through a plug of compacted powder
is the surface area of the powder.
The greater is the surface area per gram of
powder, Sw, the greater is the resistance to flow.
Hence, for a given pressure drop across the plug,
permeability is inversely proportional to specific
surface
 measurement of the former provides a means
of estimating this parameter
A plug of powder can be regarded as a series of
capillaries whose diameter is related to the
average particle size.
The internal surface of the capillaries is a
function of the surface area of the particles.
According to Poiseuille equation,

where V is the volume of air flowing through a

capillary of internal diameter d and length l in
t seconds under a pressure difference of ΔP.
The viscosity of the fluid (air) is η poise
The Kozeny–Carman equation, derived from the
Poiseuille equation, is the basis of most air
permeability methods. Stated in one form, it is
where A is the cross-sectional area of the plug,
K is a constant (usually 5.0  0.5) that takes
account of the irregular capillaries, and
ε is the porosity
Fig The Fisher subsieve sizer. An air pump generates air
pressure to a constant head by means of the pressure
regulator. Under this head, the air is dried and
conducted to the powder sample packed in the tube.
The flow of air through the powder bed is measured by
Derived properties of powders
Porosity
Suppose a nonporous powder is placed in a graduated
cylinder:
 the total volume occupied is known as the bulk volume Vb

 bulk volume (Vb) = true volume (Vp) + volume of spaces

• The volume of the spaces, the void volume, V = Vb – Vp

• The porosity or voids ε of the powder is defined as the ratio

of the void volume to the bulk volume of the packing.

Porosity = ε = Vb – Vp = 1 - Vp
Vb Vb
Porosity is frequently expressed in percent, ε x 100
Packing Arrangements
Powder beds of uniform-sized spheres can
assume either of two ideal packing
arrangements:
closest or rhombohedral
most open, loosest, or cubic packing.
The theoretical porosity of a powder
consisting of uniform spheres in closest
packing is 26% and for loosest packing is
48%.
The arrangements of spherical particles in
closest and loosest packing are shown in
Figure .
The particles in real powders are neither spherical
in shape nor uniform in size.
Thus, the particles of ordinary powders may have
any arrangement intermediate b/n the two ideal
packings
 most powders in practice have porosities b/n 30%
and 50%.
 If the particles are of greatly different sizes,
 the smaller ones may shift b/n the larger ones to
give porosities below the theoretical minimum of
26%.
In powders containing flocculates or aggregates,
 which lead to the formation of bridges and arches
in the packing, the porosity may be above the
theoretical maximum of 48%.
 In real powder systems, then, almost any degree of
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 82 cm3 when placed in a
100-ml graduated cylinder. Calculate the porosity ?
Answer = 0.5 0r 50%

Calculate the percent porosity of TiO2 having a true

density of 4.26g/cm3 and 100g sample of which

was found to occupy a bulk volume of 80 mL.
B/ Densities of particles:
 Density is physical property of powders, defined as
weight per unit volume
Types of densities:
1. True density
 True density refers to the ratio of the mass of the
particle to its actual volume
 excluding pore volume and the volume of the gap
between particles
 A helium pycnometry is commonly used method for the
determination of true density
 Helium can readily penetrate into small pores; therefore,
it is considered that the density measured by helium
pycnometry approximates the true density
 Conversely, liquids, such as water and alcohol, cannot

79
penetrate small pores, so the density measured by these
fluids is often slightly smaller than the true density
 Water or mercury
surrounds such a particle
and rests only in the
surface irregularities such
as regions A and B.
Helium molecules may
enter deep into the cracks
at points C
 Allowing calculation of true
rather than granule density
Pore size classification
 Micropores - Less than 2
nm
 Mesopores - Between 2 and
50 nm
Pores and crevices of a pharmaceutical granul
 Macropores - Greater than
50 nm
2. Granule density (g )
 The ration of the mass of the granular powder

and the volume occupied by the granular

material together with its intra particle space.
 determined by the displacement of mercury,
which does not penetrate at ordinary
pressures into pores smaller than about 10 μm
When a solid is nonporous, true and granule
densities are identical, and
both can be obtained by the displacement of
helium or a liquid such as mercury, benzene,
81 or water.
3. bulk density (b)
It is the ratio of the mass of the powder and its bulk
volume
includes the volume of all of the pores within the
sample.
The bulk density of a powder depends primarily on
 particle-size distribution,
 particle shape,
 the packaging arrangement
 the tendency of the particles to adhere to one
another.
The particles may pack in such a way as to leave
large gaps between their surfaces, resulting in a
light powder or powder of low bulk density.
 On the other hand, the smaller particles may shift
82
between the larger ones to form a heavy powder or
4. Tap density
It is the ratio of mass of powder to tapped
volume (V2 below)
is achieved by mechanical tapping a
measuring cylinder containing a powder
sample
The cylinder is mechanical tapping, and
volume readings are taken
V1 until little further
volume change is observed
V2

M
b 
V1
The intraparticle porosity of the granules can
be computed from a knowledge of the true
and granule density.
The porosity is given by the equation

where Vp is the true volume of the solid

particles and Vg is the volume of the particles
The interspace or void
porosity of a powder of
porous granules is the
relative volume of
interspace voids to the
bulk volume of the
powder
 exclusive of the
intraparticle pores.
 The interspace
porosity is computed
from a knowledge of
the bulk density and
the granule density
 Interparticle porosity is
85 calculated as
Total porosity is the sum Interparticle

porosity and Intraparticle porosity and

calculated as
but
and

where w is the mass (“weight”) of the

powder, ρ is the true density, and ρb is the

bulk density
86
Example
The granule density, ρg, of sodium
bicarbonate is 1.450 and the true density,
ρ, is 2.033. Compute the intraparticle
porosity
Example
The weight of a sodium iodide tablet was
0.3439 g and the bulk volume was
measured by use of calipers and found to
be 0.0963 cm3. The true density of sodium
iodide is 3.667 g/cm3.
What is the bulk density and the total
porosity of the tablet?
Example:
Estimate the Intraparticle porosity of
sulfadiazine granules having a granule
density of 1.12 g/cm3 and true density of
1.5g/cm3.
The granule density of sodium bicarbonate

is 1.450 g/cm3 and true density of 2.033

g/cm3 . Compute intraparticle porosity.

88
Example
The following data apply to a 1 g sample of a
granular powder:

(a) What are the specific true volume, V, the

specific granule volume, Vg, and the specific
bulk volume, Vb?
(b) Compute the total porosity, εtotal, the
interspace porosity, εinterspace, or void spaces
between the particles, and the intraparticle
89 porosity, εintraparticle, or pore spaces within the
Bulkiness
Specific bulk volume (bulkiness), the reciprocal
of bulk density
It is an important consideration in the packaging
of powders.
The bulk density of calcium carbonate can vary
from 0.1 to 1.3, and the lightest or bulkiest type
would require a container about 13 times larger
than that needed for the heaviest variety.
Bulkiness increases with a decrease in particle
size.
 In a mixture of materials of different sizes,
however, the smaller particles shift between the
larger ones and tend to reduce the bulkiness
Flow Properties
Flowability refers to the ease with which a powder
will flow under a specified set of conditions
A bulk powder is somewhat analogous to a non-
Newtonian liquid, which exhibits plastic flow and
sometimes dilatancy,
 the particles being influenced by attractive forces to
varying degrees
Accordingly, powders may be free-flowing or
cohesive (“sticky
Powder flowability is an essential property, which
has a great impact on many pharmaceutical
processes, such as
 blending, transfer, storage, compression, and
handling,
 as well as the quality of pharmaceutical dosage
Factors Affecting Powder Flowability
There are many factors that affect the flowability of
powder solids, such as
 particle size,
shape,
 porosity
density, and
Surface texture
With relatively small particles (less than 10 μm),
particle flow through an orifice is restricted
b/c the cohesive forces b/n particles are of the
same magnitude as gravitational forces.
Because gravitational forces are a function of the
diameter raised to the third power, they become
more significant as the particle size increases and
flow is facilitated
 methods for evaluating flow properties of powders &
granules
the flow properties of a powder is quantify either
 directly using dynamic or kinetic methods, or
 indirectly, generally by measurements carried out on
static beds
Hopper flow rate
 The simplest method of determining powder flowability
directly is to measure the rate at which powder
discharges from a hopper
A simple shutter is placed over the hopper outlet and the
hopper filled with powder.
The shutter is then removed and the time taken for the
powder to discharge completely is recorded.
By dividing the discharged powder mass by this time, a
flow rate is obtained
 which can be used for quantitative comparison of
Recording flowmeter
the powder is allowed to discharge from a
hopper or container on to a balance.
In the case of analogue balances a chart
recorder is used to produce a permanent
record of the increase in powder mass with
time
In some systems the signal from the balance
is digitized and processed by a microcomputer.
Recording flowmeters allow mass flow rates to
be determined
 also provide a means of quantifying
uniformity of flow.
Angle of repose
Angles of repose have been used as indirect
methods of quantifying powder flowability
because of their relationship with
interparticle cohesion
Angle of Repose (θ) is the maximum angle
between the surface of a pile of powder and
horizontal plane
Carr’s compressibility index
The percentage compressibility (Carr’s Index) can be
calculated by the following equation:

It indirect method of measuring powder flow from

bulk densities
 Hausner found that the ratio tap density
to bulk density was related to
interparticle friction
 could be used to predict powder flow
properties