Chapter-III

Micromeritics
[email protected]/Micromeritics 1/14/2025 1
Outline
• Introduction
• Particle size and size distribution
• Methods for determining particle size

• Particle shape and surface area

• Methods for determining particle surface area
• Derived Properties of powders

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Objectives
 After completion of this topic, the student should be able
to
— Understand the concept of particle size as it applies to the
pharmaceutical sciences
— Understand the application of particle size analysis in pharmacy

— Describe how particle size can be characterized and why these

methods are important
— Discuss the methods for determining particle size, and surface
area
— Describe what a fundamental and derived property of a
powder is and identify the important fundamental and derived
properties
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Introduction
 Knowledge and control of the size and the size range of
particles are of profound importance in pharmacy.

 Thus, size and hence surface area of a particle can be

related in a significant way to the physical, chemical and
pharmacologic properties of a drug.

 Clinically, the particle size of a drug can affect its

release from dosage forms that are administered
orally, parenterally, rectally, and topically.

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Introduction…
 The successful formulation of suspensions, emulsions
and tablets, from the viewpoints of both physical stability
and pharmacologic response, depends on the particle
size achieved in the product.

 In the area of tablet and capsule manufacture, control of

the particle size is essential in achieving the necessary
flow properties and proper mixing of granules and
Powders.

 These and other factors make it apparent that a

pharmacist must possess sound knowledge of
micromeretics.

1/14/2025 [email protected]/Micromeritics 5
What is
Micromeritics?

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Introduction…

Is the science and technology of small

particles that deals with fundamental and
derived properties of individual and
collection of particles

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Introduction…
 Application of particle size analysis
 The particle size of pharmaceutical materials influences
various properties of drugs and formulations, such as;
 solubility, bioavailability, stability, and manufacturability.

 Below are the key applications of particle size analysis

in pharmacy:
 Physical properties of powder
 physical properties of powder are dependent on particle size and size distribution
o Bulk density, compressibility, porosity
 Flow properties of the powder
o Spherical particles:- good flow property
o Asymmetrical particles:- poor flow property
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Introduction… Application
 Release and dissolution of drug
 Higher surface area allows intimate contact of the drug
with the dissolution fluids in vivo & increases the drug
solubility & dissolution

 Absorption and drug action

 Higher the dissolution, faster the absorption & hence
quicker & greater the drug action

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Introduction… Application…
 Physical stability
 Suspensions & emulsions
— Smaller the size of the particle, better the physical stability of the
dosage form.

 Dose uniformity
 Good flow properties of granules & powders are important in
the manufacturing of tablets & capsules
 The flow of granules should be uniform in order to ensure
precise weight of the tablet/capsule and drug content

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Properties of a particle
 Properties of a particle
— Fundamental
— Derived

 Fundamental properties
— These are properties from which other properties can be derived
 Particle size and size distribution
 Particle shape and surface area
 Particle number and weight
 Particle volume

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Properties of a particle… Particle size
What is a Particle?
 Particles are 3-dimensional objects, and unless they are perfect
spheres , they cannot be fully described by a single dimension
such as a radius or diameter.

 Particles can be
o Symmetric
o Asymmetric

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Properties of a particle… Particle size…
Symmetric particles
 The size of particles of simple geometry (e. g. spheres and cubes)
can be accurately and unambiguously determined using diameter
and edge length.
 So, for a perfect sphere;
3
π d
 Surface area, S  πd 2 Volume, V 
A
6

B C
A

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Properties of a particle… Particle size…
Asymmetric particles
— have a definite surface area and volume but being asymmetric,
its apparent length varies with its orientation

— Hence, it is not possible to express its size in terms of its

diameter

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Properties of a particle… Particle size…

Particle size instruments specify the size of

irregularly shaped particles using an
equivalent spherical diameter.

In this case, the particle size is defined by the

diameter of an equivalent sphere having the
same property as the actual particle

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Properties of a particle… Particle size…

Asymmetric
particle

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Properties of a particle… Particle size…

 Surface diameter (ds): the diameter of a sphere

having the same surface area as that of the
asymmetric particles in question.

Stock diameter (dst): the diameter of a sphere

with the same density as the asymmetric particles in
question and which undergoes sedimentation at the
same rate as the asymmetric particles in a given fluid
— dst is usually determined using sedimentation methods

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Properties of a particle… Particle size…

 Projected diameter (dp): the diameter of a sphere having

the same observed area as that of the asymmetric particles in
question when viewed normal to its most stable plane
— Usually determined using microscopic techniques

 Volume diameter (dv): the diameter of a sphere having the

same volume as that of the asymmetric particles in question.

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 Example
— Imagine a cylinder of diameter D1 =
20μm (i.e. r=10μm) and height 100μm.
— There is a sphere of diameter, D2
which has an equivalent volume to the
cylinder. We can calculate this
diameter as follows:

Volume of cylinder  πr 2 h  10000 π μm 3  

4
Volume of Sphere  πX 3  10000π μm 3
3
  Where X is equivalent volume radius

3V 3 310000 π  3
X 3   7500  19 .5  m ( r ) or 39  m(d)
4π 4π

 The volume equivalent spherical diameter for a

cylinder of 100μm height and 20μm is 39μm

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Properties of a particle…
Particle size distribution

A powder may contain

1. Mono-disperse particle
— Itscharacteristics can be described by a single diameter
or equivalent diameter

2. Poly-disperse particle
— commonly encounter in pharmaceutical powders
— mixture of particles with varying size and shape
o Can not be described by a single diameter

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Properties of a particle…
Particle size distribution…

— It is therefore necessary to know not only the size of a

certain particle, but also how many particles of the same
size exist in the sample

— Thus, weneed an estimate of the size range present and

the number or weight fraction of each particle size.

— This is called the particle size distribution and from

this, the average particle size of the collection of
particles can be derived.

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Properties of a particle…
Particle size distribution…
Average particle size
 The particle size of a powder is analyzed microscopically and the
number of particles in each size range is determined

Size range Mean size range No particle in each nd

(µm) (in µm ) (d) size range (n)
0.5-1.0 4
1.0-1.5 18
1.5-2.0 39
2.0-2.5 73
2.5-3.0 24
3.0-3.5 14
3.5-4.0 2
n=174 nd=
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Properties of a particle…
Particle size distribution…

Size range Mean size range No particle in each nd

(µm) (in µm ) (d) size range (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

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Properties of a particle…
Particle size distribution…

 From the data, the average particle size of the powder

may be calculated as
 nd
 Particle size =
n
= 377/174
= 2.16 µm

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 The particle size distribution in a powder
may be quantified by one of the following
two ways

— By determining the number of particles

present in each size range (usually
determined by microscopic method)
— By determining the weight/volume of

Frequency
particles present in each size range (usually
determined by sieving method)

 When this number or weight of particles

lying within a certain size range is plotted
against the size range or mean particle size, Particle size
a frequency distribution curve is Frequency distribution curve
obtained.

— Such frequency plots can give a visual

representation of the distribution which an
average diameter can not achieve.

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Properties of a particle…
Particle size distribution…

 When the number of particles is plotted against the

mean particle size, the curve obtained is k/n as
— The number frequency distribution curve

 When the weight of particles is plotted against the

mean particle size, the curve obtained is k/n as
— The weight frequency distribution curve

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Properties of a particle…
Particle size distribution…

 Two samples 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 which will be easily obtained from the
frequency distribution

 From frequency distribution curve

— Particle
size distribution
— The particle size which occurs most frequently

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 Frequency distribution curve…

 Example:
— Consider nine particles of which three particles are 1μm, three are
2μm, and three are 3 μm in size (diameter).

— Build a number and volume distribution for theses particles?

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 Frequency distribution curve…

% By Number = 3/9 = 33%

Size % by # % by
(m) volume
1 33 2.8
2 33 22
3 33 75

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% By Number = 3/9 = 33%
 Frequency distribution curve…
Number frequency distribution Volume frequency distribution

% Frequency (voume)
% Frequency (#)

Particle size Particle size

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 45
 A polydisperse powder is said to have a 40
35
normal distribution if a typical bell-

Frequency
30
25
shaped frequency distribution curve is 20
15
obtained. 10
5
— In such a case one half of the curve is 0
0 5 10 15 20
superimposed on the other half. Particle size
35
30

 However, normal distribution is not

Frequency
25
20
commonly found in pharmaceutical 15

powders 10
5
— More commonly, asymmetric or skewed 0
distribution is obtained 0 5 10 15 20

Particle size
35
30
— Such curve can be converted to a normal

Frequency
25
bell-shaped curve by plotting frequency 20

versus the logarithm of the particle 15

10
diameter. 5

o Log-normal distribution curve 0

0 0.5 1 1.5
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Particle size
Cumulative distribution curve
 Alternatively, a particle size distribution can be obtained by
sequentially adding the percent frequency values (Table
below) to produce a cumulative percent frequency distribution
Table Cumulative frequency distribution data

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Cumulative distribution curve…

Cumulative % frequency undersize

 Cumulative percent
frequency distribution

 Gives sigmoid curve with

the mode being the particle
size of the greatest slope.

Particle size (μm)

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 When the log of the particle size is
plotted against the cumulative percent
frequency on probability scale, a linear
relationship is obtained.
— This is known as the log probability plot and
can be characterized by two parameters
o The reference point
 Geometric mean diameter, dg
 It is the log of the p.s equivalent to
50% on the probability scale, i.e.,
the 50% size
o The slope of the line
 Geometric standard deviation, g

84% undersize or 16% oversize

g 
50% size

50% size
g 
84% oversize or 16% undersize
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[email protected]/Micromeritics
Particle Number
A significant expression in particle technology is the
number of particles per unit weight, N, which is
expressed in terms of dvn

 The number of particles per unit weight is obtained as

follows.
— Assume that the particles are spheres, the volume of
a single particle is d3/6, and the mass (volume x density)
is (d3)/6 g per particle. The number of particles per gram
is then obtained from the proportion
6
N 3
d vn 
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 The mean volume number
diameter of the powder is 2.41
m, or 2.41 x 10-4cm. If the
Solution
density of the powder is 3.0 6
g/cm3, what is the number of N 
particles per gram?
 d vn3 
6
 Given N 
3 .14 x ( 2 .41 x10  4 ) 3 x 3
—d = 2.41 x 10-4cm
—  = 3.0 g/cm3
 4 . 55 x10 10 particles
 Required
—N =?

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Distribution statistics
 Particle size (diameter) can be described by different expression

 A mean particle diameter:

— the sum of all individuals’ diameter divided by the total number of particles
— sensitive to extreme value
— represents the size present in the greatest number

 Median diameter:
— It is the middle value when numbers arranged based on their size.
— a diameter for which 50% of the particles are less the stated size

 Mode diameter:
— Represents the particle size occurring most frequently in the sample

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Methods of particle size determination
 Particle-size analysis methods can be divided into different
categories based on several different criteria:
— Measuring range required (minimum and maximum size of particle)

— Precision required

— Quantity of sample to be analyzed

— Time of analysis

— Media in which sample can be analyzed (dry or liquid)

 Hence,
— Microscopy (0.2 – 100 μm)

— Sieving (> 50 μm)

— Sedimentation rate method (0.8 - 300μm)

— Coulter counter (0.4-1200 μm)
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 Microscopy
 The effective size range for analyzing particles is about 0.2 to 100
µm.

 Procedure
— Dilute suspension of the particles, whose sizes 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 by

which the size of the particles can be determined
— The particles observed are counted

— For ease, the field can be projected or photographed

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 Microscopy…

• At least 300- 500 particles must be counted in order to obtain a

good size distribution analysis of data.

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 Microscopy…
Diameters measured
Martin's diameter (M) -1
 The length of the line which bisects the
particle image. The lines may be drawn in
any direction which must be maintained
constant for all image measurements.

Feret's diameter (F) -2

 The distance between two tangents on
opposite sides of the particle, parallel to
some fixed direction.

Projected area diameter (da or dp) -3

 The diameter of a circle having the same
area as the particle viewed normally to
the plane surface on which the particle is
at rest in a stable position.

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 Microscopy…
Advantages
 Providing a direct visual representation of the particles
 Requires an extremely small amount of sample
 The equipment is relatively inexpensive to acquire and maintain
 Aggregates as well as particles of more than one component can
be detected
 It can provide details about shape, crystal habit, and homogeneity
within the sample in addition to size

Disadvantage
 The measured diameter of the particles represents two dimensions
only
 Slow and tedious process

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 Sieving Technique

 Sieve analysis is performed using a nest or stack of

sieves where each lower sieve has a smaller aperture
size than that of the sieve above it

 Involves mechanical shaker.

 Sievingis most suitable for powders whose average

particle size > 50 μm (coarse particles)

• It is used for
 Classification of powders
 Determining the size distribution of coarse powders

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 Sieve classification

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 Pharmaceutical powders classification by finness

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Conducting sieving analysis
 A nest of sieves with the coarsest
on top is placed on the shaker, and
the powder sample of known weight
is placed on the top of the sieve &
shaken for a definite period of time.

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 The material that passes
through one sieve and is
retained on the next finer
sieve is collected and
weighed.

 Mass, collected on each

sieve
 Percentage of sample,
collected on each sieve
 Cumulative percentage of
sample retained on each
sieve

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Data presentation

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Mean Sizes
The four most common average or mean diameters employed for
describing polysize particulate masses in sieve analysis are:
Arithmetic mean
1
d a  d 1  d 2  where:
2
d1 : sieve aperture through which the
Geometric mean
particles pass.
dg  d 1 . d 2  d2 : sieve aperture on which the
Volume mean particles are retained.
w :mass/percent of particles retained
dv 
 wd a ∑ : the summation symbol.
w
Surface mean

ds 
 w
wd a
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Example

• dv and ds are 391 microns and 338 microns, respectively.

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Example cont’
 If the particles have passed through a 700 micron sieve and
been retained on a 500 micron sieve then what will be da &
dg?:
— da = (700 + 500)/2 = 600 microns, And dg = (700*500)1/2 = 591
microns.

 The diameter of particles that pass a 40-mesh sieve and are

retained on a 60-mesh sieve (i.e., 40/60) may be expressed as
the arithmetic and geometric mean of the opening of two
sieves
420  250
 335m
2
420 * 2501/ 2  324m
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 Advantage
— Simple
— low cost

— little skill for operation

 Disadvantage
— large sample size required
— blinding of the screens due to mechanical clogging

— Aggregation- due to electrostatic charge or moisture

— Attrition- size reduction

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Sedimentation method

 The sedimentation method employs the settling of

particles in a liquid of a relatively low density,
— under the influence of a gravitational or centrifugal field.

 Several methods based on sedimentation are used.

— The Andreason pipette, which is based on sampling near the
bottom of a glass sedimentation chamber, is the best known
one.
o Because it combines ease of analysis, accuracy and economy of
equipment

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1/14/2025
Sedimentation method…
• The particle size can be obtained by gravity
sedimentation as expressed in Stokes’ law (0.8 to
300µm)
Where
• v is the rate of settling (x/t)
• Stokes' Law : •x is the distance of fall in time, t
•dst is the mean diameter of the
 (x / t) 
s  o gd st
2
particles based on the velocity of
18o sedimentation (Stokes’ diameter)
• ρs is the density of the particles
•ρo is the density of dispersion
18o x medium
d st 
s  o g t •ηo is the viscosity of the medium
•g acceleration due to gravity

• This equation holds true only for particles falling freely

54 without hindrance and at a constant rate
Sedimentation…
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.

d st 
18 x0.01g / cm sec X 7.3x103 cm / sec 
5.60  1.01g / cm X 981cm / sec 
3 2

 5.40 x10  4 cm or 5.40 m

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Sedimentation…
 For Stokes’ law to apply, a further requirement is that
the flow of dispersion medium around the particle as
it sediments is laminar or stream line.

 Whether the flow is turbulent or laminar is indicated

by the dimensionless Reynold’s number, R, which is
defined

 d o
Re 
o
 Stokes’ law cannot be used if Re is greater than 0.2
because turbulence appears above this value

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Sedimentation…
• The limiting particle size under a given set of conditions
can be calculated as follows
R e d 2  s   o g
v 
do 18 
and thus
3 18 R e 2
d 
 s   o  og
EXAMPLE:
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.
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Sedimentation…
2
18 x 0 . 2 x ( 0 . 01)
d3 
( 2.7  1.0) x1.0 x 981
d  6 x10  3 cm  60 m
Example
• If the material used in the above example is flow suspended in a syrup containing
60% by weight of sucrose, what will be the critical diameter, that is the
maximum diameter for which R does not exceed 0.2? The viscosity of the syrup
is 0.567 poise, and the density is 1.3 g/cm3.

2
18 x 0 . 2 x ( 0 . 567 )
d3 
( 2.7  1.3) x1.3 x 981
d  8.65 x10  2 cm  865 m
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Sedimentation techniques
 Andreasen pipette is used for particle size distribution
determination

• 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

cm below the surface of the
suspension
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 18o x
Sedimentation… d st 
s  o g t
Size distribution is determined as follow

— Allow a homogeneous suspension(1-2%) placed in

the vessel up to 550 ml mark to settle in a cylinder
— Left undisturbed in constant temperature bath

— Take 10 ml sample from the settling suspension at a

fixed horizontal level at intervals of time.
— Evaporate and weigh the samples

— This concentration expressed as a percentage of

the initial concentration gives the percentage (w/w)
of particles whose falling velocities are equal to or
less than x/t.
— Substitution in the equation above gives the
corresponding Stokes' diameter.
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Sedimentation…
Advantage
— The apparatus is inexpensive and the technique is simple

— The results obtained are precise provided the technique is

adequately standardized

Disadvantages
— Method is laborious since separate analysis are required for each
experimental point on the distribution curve

— Very small particles cannot be determined accurately since their

settling is unduly prolonged

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Coulter Counter Method

 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.

 Powder samples are dispersed in the electrolyte to form a very

dilute suspension.

 A known volume of the suspension is pumped through the orifice

so that only one particle passes at a time through the orifice

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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 b/n the two electrodes.

 The change in the electrical resistance b/n the electrodes

that is proportional to the volume of the particle is
converted in to a voltage pulse that is amplified and
processed electronically.

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64 [email protected]/Micromeritics 1/14/2025
 Advantages
— Evaluation is fast.
— Since a large number of particles are counted, the results are
more reliable
— Since the aperture is automatic, operator variability is avoided

 Disadvantage
— The sample must be suspended in an electrolyte.
o In many cases the fluid in which the particles are suspended is non-
conducting.
— Aggregation of particles can give false results

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Derived properties of powders

— Porosity

— Density

— Bulkiness or specific bulk volume

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Derived properties of powders
Porosity of powder
The quality or state of being porous or the proportion of a
powder bed or compact that is occupied by pores.
 It is a measure of the packing efficiency of a powder
 Powders can be
i. Porous (most pharmaceutical solids are porous, i.e., they have
Inter-connected
internal pores or capillary)
(open) Closed
 Bulk volume > true volume

ii. Non-porous

Passing (open)

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 Porosity…
When a 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 b/n particles

The volume of the spaces, the void volume,

V = Vb – Vp
 The porosity (ε) of powder is determined as the ratio of void
volume to bulk volume. ε =
V

Vb  Vp Vp
Frequently expressed in percent, ε x 100 ε 1
Vb Vb

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 Porosity…

Packing arrangement in Powder Beds

 Two types of packing are possible

Rhombohedral packing Cubic packing

 Closest packing (=26%) Most open/ Loosest packing(=48%)

ε = 26% ε = 48%

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 Porosity…

 Pharmaceutical powders have porosity range from 30 to 50%.

 When the particles of varying sizes are present, porosity lower

than the theoretical minimum of 26% is also possible.Why ?

 If the powder contains floccules or aggregates, the porosity may

go beyond the theoretical maximum of 48%.Why ?

 Highly compressed crystalline materials,  < 1%

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 Examples on porosity
Example
 A sample of calcium oxide powder with a true density of 3.203 and
weighing 131.3 g was found to have a bulk volume of 82 cm3 when
placed in a 100-ml graduated cylinder. Calculate the porosity ?
 Ans.=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.
 Ans=70%

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 Density of powder
 Density is defined as weight per unit volume (W/V).
— The difficulty arises when one attempts to determine the
volume of particles containing microscopic cracks, internal
pores, and capillary spaces.

 Based on the method of determination, three types of

densities can be defined
— (a) the true density of the material itself, exclusive of the
voids
— (b) the granule density as determined by the displacement of
mercury, which does not penetrate at ordinary pressures into
pores smaller than about 10 m, and
— (c) the bulk density as determined from the bulk volume and
the weight of a dry powder in a graduated cylinder
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 Density of powder
A- True density
 The true density, or absolute density, of a
sample excludes the volume of the pores and
voids within the sample.

 Methods
 Gas displacement method (He, H2)
 better penetration ability

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 Density of powder…
B. Granule density (g )
 Mass of the granular powder and the volume occupied by
the granular material together with its intra particle space
— Method-using Liquid displacement Method (Mercury)

Vg Vp Vp ρg
εintra 1 1
Vg Vg ρp

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 Density of powder…

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 Density of powder…
C- Bulk density (b)
— Itis the ratio of the mass of the powder
and its bulk volume
— Includes the volume of all of the pores
within the sample.

—A sample of powder is carefully introduced

into a 100 mL graduated cylinder.

— The cylinder is dropped onto a hard wood

surface three times from a height of 1 inch.
o The hulk density is then obtained by dividing the
weight of the samp1e in grams by the final
volume in cm3 of the sample contained in the
cylinder.
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 Density of powder…

C2.Tapped density (T)

 It is the ratio of mass of powder to tapped volume
— Tapped volume
o the volume of the powder obtained after tapping the powder 250 times using Tap
Densitometer

M
V1 ρb 
V1
V2
M
ρT 
V2
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 Density of powder…

Tap densitometer
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 Density of powder…

Example:
 Estimate the Intraparticle porosity of sulfadiazine granules having a
granule density of 1.12 g/cm3 and true density of 1.5g/cm3.

VgVp Vp ρg
εintra 1 1
Vg Vg ρp

 Ans=25.3%

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 Bulkiness or specific bulk volume
 It is the reciprocal of bulk density and k/n as
— Bulk, bulkiness, or specific bulk volume

 Bulkiness usually increases with a decrease in particle

size.
— However, in a mixture of particles with different sizes,
the bulkiness may get reduced.

Application of Bulkiness
— It is a useful property to be considered while choosing a
suitable container for packaging or during filling of drug
powders in to capsules.

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 Flow properties of powders
• Important parameter to be considered in the
production of pharmaceutical dosage forms.

• Example:
 Uniform filling of dies during tableting, and
 Proper filling of capsules during capsule
filling
 directly depends on the flow properties of
the powder

• Based on their flowability, the pharmaceutical

powders are classified as:
 Free-flowing : easily flowing
 Cohesive (“sticky”) or non-free-flowing: do
not flow as readily as possible

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 Flow properties of powders…
The poor flow in powders is attributed to:
1) 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
 Density or porosity of the powders
 Dense materials tend to be less cohesive than lighter ones

 The presence of adsorbed materials on the powder surface

 Moisture increase cohesiveness of particles

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 Flow properties…
2) Adhesion between the particles and the container wall
due to the above forces.

3) Friction between particles due to surface roughness

4) Physical interlocking of particles specially if these are of

irregular shape

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 Flow properties…
 Many common manufacturing problems are attributed to
powder flow:

 Uneven powder flow

 Excess entrapped air within powders → capping or
lamination
 Increase particle’s friction with die wall causing lubrication
problems, and
 Increase dust contamination risks during powder transfer
 Non-uniformity of dose

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Assessment of flow properties of powders

 Flow properties of powders can be assessed by

— Angle of repose

— Compressibility index and Housener ratio

— Flow rate

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Assessment of flow properties of powders…

 Angle of repose
— Angle of repose is a function of the surface
roughness

The rougher and more irregular the surface of

particles, the more the angle of repose

— As the particles become less and less spherical, the

angle of repose increases while the bulk density and
flowability decreases
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Assessment of flow properties of powders…

—A sample of powder will be made to flow through a

funnel, on to a graph paper from a certain height.
The height (h) as well as the diameter (d) of the pile
will be measured.
Then the angle of repose () was calculated from
h and radius (r = d/2) using Equation

tan   h / r
1
  tan (h / r )

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Assessment of flow properties of powders…

Angle of repose () Flow properties

<25o Excellent

25 – 30o Good

30 – 40o Satisfactory

40 – 50o Poor

>50o Very poor

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Assessment of flow properties of powders…
 Compressibility index (Carr’s Index) and
Hausner ratio
— Hausner ratio is related to the interparticle friction

— The compressibility index (CI) and Hausner ratio are

calculated from bulk and tapped densities, using Equation

Compressibility Index 
t  b  x100
t

t
Hausner ratio 
b

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Assessment of flow properties of powders…

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Assessment of flow properties of powders…

 Flow rate
— The flow rate through an orifice is measured as the mass per
time flowing from any of a number of types of containers
— Useful for only free flowing materials

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 Improvement of the flow properties of powders

Flow properties of powders can be improved by one of the

following methods

1) Alteration of particle’s size and distribution

— particle size  improves flow property

o Due to reduction in cohesive forces

— Coarse particles are more preferred than fine ones as

they are less cohesive.

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 Improvement…

2) Alteration of particle shape and texture

— Particle’s shape: generally, more 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
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 Improvement…
3) Alteration of surface forces
— Reduction of electrostatic charges can improve powder flowability.
o Altering process conditions to reduce frictional contacts

4) Removing extra moisture

— Moisture content of particle greatly affects powder’s flowability
o Drying the particles will reduce the cohesiveness and improve the flow.
o Hygroscopic powders, stored and processed under low humidity conditions.

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 Factors affecting…

5) Formulation additives ( Flow activators)

— Flow activators are commonly referred as glidants.
— Flow activators improve the flowability of powders by reducing adhesion
and cohesion.
— e.g. talc, maize starch and magnesium stearate

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96 [email protected]/Micromeritics 1/14/2025
 IPPP-II
Chapter - 4

Powders and
granules
1/14/2025
[email protected]/Micromeritics By: Zewdu Yilma 97
 Introduction
Dosage forms
 Definition:
— the means by which drug molecules are delivered to sites of action within the
body.

 Can be classified as follows

— Based on route of administration
o Oral
o Topical
o Parenteral
o Vaginal
o Rectal
o Inhaled
o Ophthalmic
o Otic
— Based on their physical form
o Solid
o Liquid
o Semisolid

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Introduction…
 Solid dosage forms include
— Powders,
— Granules,

— Capsules, and

— Tablets

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 Powders
 Powders are dry mixtures of finely divided medicinal and
non-medicinal agents intended for internal or external
use.
 Powders represent one of the oldest dosage forms

 Powders may be dispensed to a patient as

— Divided powders (single dosage units), or

o are dispensed in the form of individual doses and generally are dispensed
in papers, properly folded.
o They also may be dispensed in metal foil, small heat-sealed plastic bags, or
other containers
— Bulk powders (multiple)

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Powders…

 Bulk powders
— Are powders which are dispensed in large quantity or
containing multiple doses
— Bulk powders may be classified as
o Oral powders,
o Dentifrices,
o Douche powders,
o Dusting powders,
o Insufflations, and
o etc

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Powders…

Oral powders
— generally supplied as finely divided powders.

— The finely divided powders are intended to be suspended

or dissolved in water or mixed with soft foods prior to
administration.

o Antacids (e.g., sodium bicarbonate) and

o Laxative powders (e.g., psyllium) are frequently administered in
this form.

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Powders…

 Dentifrices
— Dentifrices may be prepared in the form of a bulk powder,
generally containing a soap or detergent, mild abrasive,
and an anticariogenic (anti tooth decay) agent.

 Douche powders
— Douche powders are completely soluble and are intended
to be dissolved in water prior to use as antiseptics or
cleansing agents for a body cavity.

— They are most commonly intended for vaginal use, although

they may be formulated for nasal, otic, or ophthalmic use
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Powders…

Dusting powders
— Dusting powders are locally applied nontoxic preparations that
are intended to have no systemic action.

— They are applied to various parts of the body as

o lubricants, protectives, absorbents, antiseptics, antipruritics,
astringents, and antiperspirants.

— Dusting powders always should be dispensed in a very fine

state of subdivision to enhance effectiveness and minimize
irritation.

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Powders…

Insufflations
— Insufflations are finely divided powders introduced into body cavities
such as the ears, nose, throat, tooth sockets, and vagina.

— An insufflator (powder blower) usually is employed to administer

these products.
o However, the difficulty in obtaining a uniform dose has restricted their
general use.

— Specialized equipment has been developed for the administration of

micronized powders of relatively potent drugs.
o The Norisodrine Sulfate Aerohaler Cartridge (Abbott)
o The Spinhaler turbo-inhaler (Fisons)
o Pressure aerosols

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Preparation of powders

 In
both the manufacturing and extemporaneous
preparation of powders, the following general
techniques are applied.

— Reduction of particle size of all ingredients to the same

range (to prevent stratification)
o Trituration
o Pulverization
o Levigation

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Preparation of powders…

— Sieving

— Weighing of each ingredient.

— Mixing.
o Spatulation (spatula + tile)
o Trituration (mortar + pestle)
o Tumbling (wide mouth closed container)

— Packaging
o Divided
o Bulk

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Preparation of powders…
 However, the following procedures should receive special
attention.

— Use of geometric dilution for the incorporation of small amounts

of potent drugs.

— Reduction of particle size of all ingredients to the same range to

prevent stratification of large and small particles.

— Sieving when necessary to achieve mixing or reduction of

agglomerates, especially in the preparation of dusting powders or
powders into which liquids have been incorporated.

— Heavy trituration, when applicable, to reduce the bulkiness of a

powder.

— Protection against humidity, air oxidation, and loss of volatile

ingredients.
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Steps in geometric dilution
1. Weigh ingredients
2. Place the ingredient with the smallest quantity in a mortar.
3. Combine this powder with an amount of the material present
in the second largest quantity approximately equal to the
amount already in the mortar.

4. Triturate the powders until a uniform mixture is formed.

5. Add another amount of the second ingredient equal in size to

the powder volume already in the mortar and triturate well.

6. Continue adding powder to the mortar in this fashion until all

the powder ingredients have been added.

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Problems encountered in powder
formulation
1- Hygroscopic and Deliquescent Powder
 Problem:
— Absorption of moisture from air leading to partial or complete
liquefaction.

 Solution:
— Apply in a granular form to decrease the exposed surface to
air
— Pack in aluminum foil or in plastic film packets
— Addition of adsorbent materials such as starch
 Examples: -
— halide salts (ex. Sod. Iodide)
— Certain alkaloids (physostigmine Hcl)
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Problems encountered…

2- Efflorescent powders

 Problem:
— Crystalline substances which during storage loose their water
of crystallization and change to powder (to be efflorescent).
— The liberated water convert the powder to a paste or to a
liquid.

 Examples:
— Alum- atropine sulfate- citric acid- codeine phosphate…

 Solution:
— Using the anhydrous form, and treating it in a manner similar
to hygroscopic powders

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Problems encountered…

3- Eutectic Mixtures
 Problem:
— mixture of substances that liquefy when mixed, rubbed or triturated
together.
— The melting points of many eutectic mixtures are below room
temperature.

 Examples:
— menthol- thymol- phenol- salol- camphor…….

 Solution:
— using inert adsorbent such as starch, talc, lactose to prevent
dampness of the powder
— dispensing the components of the eutectic mixture
separately.
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Granules
 Granules
— are prepared agglomerates of powdered materials, may be used
per se for the medicinal value of their content, or they may be
used for pharmaceutical purposes, as in making tablets.

 Advantages
— Granules flow better than powders
— Granules increase compressibility

— Granules are more stable b/c they have smaller surface area

— Granules produce particle-size uniformity, thus content

uniformity.

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Methods of granulation
1. Wet Granulation
 In wet granulation,
— a liquid binder or an adhesive is first added to the powder
mixture.
— The wetted mass is then passed through a screen of the
desired mesh size, and resulting granules are dried.
— The dried granules can be passed through a second screen of a
smaller mesh to reduce the size of the granules even further.

 Over-wetting usually results in granules that are too hard for

proper tableting, while
 Under-wetting usually results in the preparation of tablets that
are too soft and tend to crumble.
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Methods of granulation …

2. Dry Granulation
 In dry granulation,
— granules are formed by compacting large masses of the powder
mixture and subsequently crushing into pieces.
— These pieces are then sized into smaller granules.

 The dry-granulation method requires the drug to have

cohesive properties for the large masses to be formed.

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 Granules as dosage forms

Effervescent Granules
 Effervescent granules contain sodium bicarbonate and either
citric acid, tartaric acid, or sodiumbiphosphate in addition
to the active ingredients.

 On solution in water, carbon dioxide is released because of the

acid-base reaction.

 Citric acid: 3 NaHCO3 + C6H8O7.H2O = C6H5Na3O7 + 3 CO2 + 3 H2O

 Tartaric acid: 2 NaHCO3 + C4H6O6 = C4H4Na2O6 + 2 CO2 + 2 H2O

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 Granules…

 Theliberated carbon dioxide has the following

advantages:
— It masks the bitter and nauseous taste.
— It promotes gastric secretions.

— It acts as a carminative.

— psychological impression at the patient

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Advantages & disadvantages of powders and
granules
Advantages of powders and granules :
1. Solid preparations are more stable than liquid preparations. e.g the
shelf life
 powders for antibiotic syrups, is 2 to 3 years,
 reconstituted with water it is 1 to 2 weeks.
2. Powders and granules are convenient forms in which to dispense
drugs with a large dose.
 E.g if the dose of a drug is 1 to 5 g it is not feasible to
manufacture tablets.
3. Orally administered powders & granules of soluble medicaments
have a faster dissolution rate than tablets or capsules
4. Powders offer a lot of flexibility in compounding solids.

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 Advantages & disadvantages…

Disadvantages of powders and granules :

1. Bulk powders or granules are far less convenient for patients to
carry than a small container of tablets or capsules.
2. The masking of unpleasant tastes may be a problem with this type
of preparation.
3. Bulk powders or granules are not a good method of administering
potent drugs with a low dose. why ????
4. Powders and granules are not a suitable method for the
administration of drugs that are inactivated in the stomach
5. Powders and granules are not well suited for dispensing
hygroscopic or deliquescent drugs.

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