Chapter-III

Micromeritics
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
— 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

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
 Study of particle size and size distribution has
many applications, like
 Physical properties of powder
 are dependent on particle size and size distribution
Bulk density, compressibility, Porosity

 Flow properties of the powder
 Spherical particles:- good flow property
 Asymmetrical particles:- poor flow property

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Introduction… Application
 Release and dissolution
 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;
π d 3
 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 circle 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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NB:- Equivalent spherical diameters for irregularly shaped particles
determined in different ways are not numerically equal.
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Properties of a particle…
Particle size distribution

A powder may contain

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

2. Poly-disperse particle
— commonly encounter in pharmaceutical powder
— 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, we need 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 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 particles
present in each size range (usually determined
by sieving method)

Frequency
 When this number or weight of particles lying
within a certain size range is plotted against the
size range or mean particle size, a frequency
distribution curve is obtained.
Particle size
Frequency distribution curve
 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.

 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 these 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

% By Number = 3/9 = 33%

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 Frequency distribution curve…
Number frequency distribution Volume frequency distribution

% Frequency (voume)
% Frequency (#)

Particle size Particle size

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 A polydisperse powder is said to 45
40

have a normal distribution if a

35

Frequency
30
25
typical bell-shaped frequency 20
15
distribution curve is obtained. 10
5

— Insuch a case one half of the curve is 0

0 5 10 15 20

superimposed on the other half. Particle size

35

 However, normal distribution is not 30

commonly found in pharmaceutical

25

Frequency
20

powders 15
10

— More commonly, asymmetric or 5

skewed distribution is obtained 0

0 5 10 15 20
Particle size
— Such curve can be converted to a 35

normal bell-shaped curve by plotting 30

frequency versus the logarithm of the 25

Frequency
20
particle diameter. 15
10
o Log-normal distribution curve 5
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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 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

— 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
— Prepare Dilute suspension of the particles
— Place a drop of suspension on the slide

— fit the eyepiece of the microscope with micrometer by which the

size of the particles can be determined
— Count the particles observed
o 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, direction maintained
constant.

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 small amount of sample
 equipment is relatively inexpensive to acquire and maintain
 Aggregates as well as particles of more than one component can
be detected
 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.

 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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Example cont’
 If the particles have passed through a 700 micron sieve and
been retained on a 500 micron sieve then:
— da = (700 + 500)/2 = 600 microns, And dg = •
(700x 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

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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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Sedimentation method…
• The particle size can be obtained by gravity
sedimentation as expressed in Stokes’ law (0.8 to
300µm)

• Stokes' Law :
Where
• v is the rate of settling (x/t)
•x is the distance of fall in time, t
ρs  ρo gd st
2
•dst is the mean diameter of the
ν (x / t)  particles based on the velocity of
18ηo sedimentation (Stokes’ diameter)
• ρs is the density of the particles
18o x •ρo is the density of dispersion
d st 
s  o g t medium
•ηo is the viscosity of the medium
•g acceleration due to gravity
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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 
18x0.01g / 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 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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50 Micromeritics 11/8/2024
 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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Recap
 Particle size distribution  Frequency distribution
can be quantified — Normal
— Skewed
 By # of particles present
in each size range  Cumulative frequency dist
 By wt of “ — Sigmoidal curve
 Particle
#
 Methods of ps
 When # or Wt of determination
particles plotted — Microscopy
against particle size — Sieving
— Sedimentation
 Frequency distribution
— Coulter counter
 # & wt

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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
internal pores or capillary) Inter-connected
(open)
 Bulk volume > true volume Closed

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.
Vb  Vp Vp
ε 1
Vb Vb
Frequently expressed in percent, ε x 100
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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
 Liquid displacement method
 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
ε intra   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
ε intra  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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Micromeritics
 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
  tan (h / r )
1

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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 were

calculated from bulk and tapped densities, using Equation

Compressib ility 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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Summary
• Derived powder properties • Assessment of flow property
 Porosity of powders
 Porous  Angle of repose
 Non-porous  CI/HR
 Density  Flow rate
 True • How to improve flow
 Granular
 Alteration of particle size,
 Bulk shape, texture, surface forces
 Bulkiness  Removing extra moisture
• Flow properties of powders  Addition of flow activators
 Free flowing
 Cohesive

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84 Micromeritics 11/8/2024
 IPPP-II
Chapter - 4

Powders and
granules
11/8/2024
Micromeritics By: Zewdu Yilma 85
 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 by intervention
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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Quiz 2
1. Mention three methods of particle size determination

2. Write the two packing arrangements found in powder bed

3. How could you improve the flow properties of powders

4. Write the steps of powder preparation

5. In what form that powders are packed or dispensed

6. What is the difference b/n powders and granules

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Quiz 1

 What is micromeritics

 Write some application of micromeritics in pharmacy

 What are the fundamental properties of particles

 Ifthe particle is non sphere, how can we determine its

diameter

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