Micromeritics

JOHN M. (B.pharm, Msc in pharmaceutics)

Lecturer
department of pharmacy
college of medicine and health sciences
(Wollo University)

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Outline

• Micromeritics and Solid dosage forms

– Micromeritics
• Particle size and size distribution
• Methods for determining particle size
• Particle shape and surface area
• Properties of powders

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Micromeritics……………

• The term micromertics was introduced by Dallavale in 1948 to

describe the science of small particles.

• Brought together information on particle size measurement, size

distribution, and packing arrangements.

 Definition:
It is the science and technology of small particles
deals with fundamental and derived properties of individual
and collection of particles

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• In the field of pharmacy, micromertics has become an important
area of study because it influences a large number of parameters

• Research and development

• manufacturing of dosage forms such as
 suspension to be reconstituted
 tablet
 capsule

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 Study of particle size and size distribution has many application in
pharmacy

 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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 Release & dissolution
• Higher surface area allows intimate contact of the drug
with the dissolution fluids in vivo & increases the drug
solubility & dissolution

 Absorption & drug action

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

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 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

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Fundamental properties of collection of particles
• 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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 Particle size and size distribution

• Particle shape plays an important role in particle size

determination

• Particles possess different shapes, for example, rod, cubical,

granular, etc

• The size of a spherical particle can be easily expressed in terms of

its diameter

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A B C

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Particle size and size distribution…………

• Particles can be asymmetric and symmetric

• The size of a spherical particle can be easily expressed in terms of its
diameter

• So, for a perfect sphere;

2
• surface area, S   d

d3
• Volume, V
6

• Non-spherical particles also has 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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• various equivalent diameters have been developed to relate the
size of such particles to that of a sphere with identical diameter,
surface area, or volume.

• Surface diameter , ds the diameter of a sphere having the same

surface area as that of the asymmetric particles in question.

• Volume diameter, dv the diameter of a sphere having the same

volume as that of the asymmetric particles in question.

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 Asymmetric particle

Different Equivalent Spheres

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• 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

• 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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• Any collection of particles is polydisperse
 mixture of particles with varying size and shape

• 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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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 (µm) Mean size range No particle in each nd
(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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• From the data the average particle size of the powder may be
calculated as

• Particle size =  nd
n

= 377/174
= 2.16 µm

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Particle size distribution

The particle size distribution in a powder may be

quantified(expressed or measured) by;

1. determining the number of particles present in each size range

2. determining the weight of particles present in each size range

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• 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

 number frequency distribution curve

number of particles vs mean particle size
 weight frequency distribution curve
weight of particles vs mean particle size

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FIGURE . A frequency distribution plot. 20
• Two sample of powder may have the same average diameter
but may not have the same frequency distribution.

• So, expression of the size in terms of average diameter may

not give a clear expression of the particle size distribution

• From frequency distribution curve

 particle size distribution
 the particle size which occur most frequently

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• Particle size can be expressed in two
ways
1. Monodisperse particle size
• its characteristics can be described by a
single diameter or equivalent diameter

2. Polydisperse particle size- common

% frequency
encounter in pharmaceutical powder
• A poly dispersed powder system is said
to have a normal distribution if a typical
bell shaped frequency distribution curve
is obtained
Particle size
Fig. normal or Gaussian size frequency distribution
curve

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• However, normal distribution is not common in pharmaceutical
powder which are commonly processed by milling or
precipitation

• More commonly asymmetric or skewed distribution is obtained

• A frequency curve with an elongated tail towards higher size

ranges is positively skeiwed; the reverse case exhibits negative
skewness.

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Fig. Frequency distribution curves corresponding to (a) a normal distribution,
(b) a positively skewed distribution and (c) a bimodal distribution.

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• Such a curve can be converted to a normal bell shaped curve
by plotting frequency vs the logarithm of the particle size
diameter
log-normal distribution curve

% frequency

Log particle size

Fig. log normal distribution curve obtained for a polydisperse powder

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• Alternatively, a particle size distribution can be obtained by
sequentially adding the percent frequency values (Table 2) to
produce a cumulative percent frequency distribution

• If the addition sequence begins with the coarsest particles, the

values obtained will be cumulative percent frequency oversize;

• The reverse case produces a cumulative percent frequency

undersize

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Table 2 Cumulative frequency distribution data

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 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.

• Geometric mean diameter.
It is the log of the p.s equivalent to 50% on the probability
scale, i.e., the 50% size.

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 Cumulative % frequency under size (probability scale)

Fig. Log probability plot

Particle size (µm)

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• 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

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• 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
 nd 3
per unit volume.
 n2
dave =
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 assignment
• How to describe particle size distributions quantitatively
• Skewness
• Kurtosis is the sharpness of the peak of a frequency
distribution curve

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 Methods of particles determination

• Particle-size analysis methods can be divided into different

categories based on several different criteria:
• size range of analysis
• wet or dry methods
• manual or automatic methods
• speed of analysis
Hence,
• Microscopic
• Sieving technique
• Sedimentation
• Coulter counter
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 Microscopy
• 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 0.25
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
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• 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.

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 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

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• Disadvantage

 The measured diameter of the particles represents two

dimensions only

 Slow and tedious process

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 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)

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40
In determining particle size by this method,

• 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 powder is classified as having passed through one sieve

and being retained on the adjacent finer sieve.
 Mass, collected on each sieve
 Percentage of sample, collected on each sieve
 Cumulative percentage of sample retained on each sieve

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• Particle diameter is considered as the size of the arithmetic or
geometric mean of the opening of the two sieves.

• Whichever size is chosen, it should be stated and used

throughout the study.

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• For example, 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 mean of the opening of two sieves

• The size of the particles can also be expressed as the geometric

average of the two sieve openings:

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• The weight of the powder retained on each sieve is weighed and,
assuming log-normal distribution, the cumulative percent by weight
of powder retained is plotted on a probability scale against the
logarithm of the arithmetic mean size of the opening of two
successive screens.

• Disadvantage
 aggregation- due to electrostatic charge or moisture
actual size is not determined
 Attrition- size reduction
 Sieve loading and duration of mechanical shaking can influence the
results
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Sedimentation
• Anderson pipette is used for particle size distribution
determination

• The particle size in sub-sieve range can be obtained by gravity

sedimentation as expressed in Stokes’s law (0.8 to 300µm)

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 Anderson pipette

• 550 ml stopper 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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• 1 or 2% suspension of the powder is placed in the vessel up to
550 ml mark.
• Shacked 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
•

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• 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 is the distance of fall in time
 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
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• 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 since separate analysis are required for

each experimental point on the distribution curve
2. Very small particles cannot be determined accurately since
their settling is unduly prolonged
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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.

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• 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 stream line.
• Whether the flow is turbulent or laminar is indicated by the
dimensionless Reynolds number, R, which is defined

• According to Heywood.’ Stokes’s law cannot be used if R is

greater than 0.2 because turbulence appears at this value.

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 • the limiting particle size under a given set of conditions can be
calculated as follows

EXAMPLE 18-41
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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E.g 2
• 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.

d =8.65 x 10-2cm = 865µm

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 Method for Particle Volume Measurement

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
• 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.
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55
 Derived properties of powders

1. Porosity of powder
The quality or state of being porous
• Powders can be
i. Porous (most pharmaceutical solids are porous, i.e., they
have internal pores or capillary)
 Bulk volume > true volume
ii. Non-porous

When a powder, is placed in a graduated cylinder: the total volume

occupied is known as the bulk volume Vb .
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• 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.

• Porosity = ε = Vb – Vp = 1 - Vp
Vb Vb
• frequently expressed in percent, ε x 100

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• Packing Arrangement in Powder Beds
• Two types of packing are possible

• Cubic packing Rhombohedral packing

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

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• pharmaceutical powders have porosity range from 30 and 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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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 ?
• 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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2. Densities of particles:
Density is defined as weight per unit volume (W/V).
Types of densities:
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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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  V p Vp g
 int ra  1  1 
Vg Vg p

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C- 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.

• Weighed quantity of the powder material is introduced into a

graduated measuring cylinder and is tapped mechanically or
manually till a constant volume is obtained.

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• This volume, known tapped volume of the powder is noted
and includes the true volume of the powder as well as the
volume occupied by the interparticle and intraparticle spaces.
D. Tapped density (T)
• It is the ratio of mass of powder to tapped volume

V1 M
b 
V1
V2

M
T 
V2
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Tappe densitometer

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

Vb  V g Vg b
 int er  1  1 
Vb Vb g
• Ans=25.3%

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3. Bulkiness = Specific bulk volume

 The reciprocal of bulk density

 Bulkiness usually increases with a decrease in particle size.
However, in a mixture of particles with different sizes, the
bulkiness may get reduced. Why??

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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• The bulk density of calcium carbonate vary from 0.1 to 1.3,
and the lightest (bulkiest) type require a container about 13
times larger than that needed for the heaviest variety.

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4. Flow properties of powders

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

 Important parameter to be considered in the production of
pharmaceutical dosage forms.

• Example:
 dies filling during tableting
 capsules filling
directly depend on the flow properties of the powder

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 Flow properties of powders depends on;
i. Cohesiveness or stickiness between particles due to presence
of Van der Waals, surface tension and electrostatic forces.
• Cohesiveness of particles has been found to depend upon a
number of factors
a. Particle size and shape
 Very fine particles tend to be more cohesive due to their
large surface area
b. Density or porosity of the powders
 dense materials tend to be less cohesive than lighter
ones
c. The presence of adsorbed materials on the powder surface
 Moisture increase cohesiveness of particles

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ii. Adhesion between the particles and the container wall due to
the above forces.

iii. Friction between particles due to surface roughness.

iv. Physical interlocking of particles specially if these are of

irregular shape

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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
- non-uniformity (segregation) in blending

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Assessment of flow properties of powders
1- Carr’s compressibility index

• Bulk density = weight / bulk volume

• Tapped density = weight / true volume

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• Relationship between powder flowability and % compressibility

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2- Hausner ratio:
• Hausner ratio was related to interparticle friction:

• Value less than 1.25 indicates good flow

• The powder with low interparticle friction, such as coarse
spheres.
• Value greater than 1.5 indicates poor flow
• more cohesive, less free-flowing powders such as flakes.

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• Between 1.25 and 1.5, added glidant normally improves flow.
• > 1.5 added glidant doesn’t improve flow.

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 3.Angle of Repose ()
• The sample is poured onto a horizontal surface and the angle of
the resulting pyramid is measured.
• The user normally selects the funnel orifice through which the
powder flows slowly and reasonably constantly.
h
tan  
r

where,
, angle of repose, h & r are height and radius of the
powder, respectively

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• 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.

• Angle of repose ( ) Flow properties

<25o excellent
25 – 30o good
30 – 40o satisfactory
40 – 50o poor
>50o very poor

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Factors affecting the flow properties of powders
Alteration of Particle’s size & Distribution
• There is certain particle size at which powder’s flow ability is
optimum.

• Coarse particles are more preferred than fine ones as they are
less cohesive.

• The size distribution can also be altered to improve flowability by

removing a proportion of the fine particle fraction or by
increasing the proportion of coarser particles, such as occurs in
granulation.

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Alteration of Particle Shape & 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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Alteration of Surface Forces
• Reduction of electrostatic charges can improve powder
flowability. Electrostatic charges can be reduced by altering
process conditions to reduce frictional contacts.
• Moisture content of particle greatly affects powder’s flowability.
• Adsorbed surface moisture films tend to increase bulk density
and reduce porosity.
• Drying the particles will reduce the cohesiveness and improve the
flow.
• Hygroscopic powders, stored and processed under low humidity
conditions.

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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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84
solid oral dosage forms

85
• Oral dosage forms are taken orally
 a local effect in the mouth, throat, or GIT
a systemic effect in the body after absorption from the
mouth or GIT.

• Oral dosage forms can be divided into two main groups

 solid DF
 liquid DF

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• Solid oral dosage forms
1. Powder and granules
2. Tablets
3. Capsules

• conventional oral solid dosage forms will be defined as those solid

dosage forms taken by or given orally to patients and intended to
deliver the drug to the site of action without any time delay

87
 Powders and granules
• Powders are dry mixtures of finely divided medicinal and non-
medicinal agents intended for internal or external use.

• Powders may be dispensed to a patient

• Multiples dose (bulk form such as powders measured
by the spoonful to make a douche solution)
• Single dosage units

88
• Powders represent one of the oldest dosage forms.

• However, with the increased use of highly potent compounds,

they have been largely replaced by
capsules and tablets.

• In certain situation, powders still possess advantages

 powders disperse & dissolve more readily than compacted
dosage forms.
 Children and adults who have trouble swallowing tablets or
capsules may find powders more acceptable.
89
1. Oral Powders
• Oral powders generally can be supplied as finely divided
powders or effervescent granules.
• The finely divided powders are suspended or dissolved in
water or mixed with soft foods such as applesauce before
administration.
• Antacids and laxative powders
• Powdered antibiotic syrups to be reconstituted before
administration are also classified as oral powders.

90
2. Douche Powders
• Douche powders are completely soluble and are dissolved in
water prior to use as antiseptics or cleansing agents for a body
cavity.

• They most commonly are intended for vaginal use, although

they may be formulated for nasal, otic, or ophthalmic use.

91
3. Insufflations
• Insufflations are finely divided powders introduced into body
cavities such as the throat.
• An insufflator (powder blower) usually is employed to
administer these products. The Norisodrine Sulfate Aerohaler
Cartridge (Abbott) is an example.
• In the use of this aerohaler, inhalation by the patient causes a
small ball to strike a cartridge containing the drug. The force
of the ball shakes the proper amount of the powder free,
permitting its inhalation.

92
• Another device, the Spinhaler turboinhaler (Fisons), is a
propeller-driven device designed to deposit a mixture of
lactose and micronized cromolyn sodium into the lung as an
aid in the management of bronchial asthma. However, the
difficulty in obtaining a uniform dose has restricted their
general use.

93
4. Oral Antibiotic Syrups
• For patients who have difficulty taking capsules and tablets,

• but many antibiotics are physically or chemically unstable

when formulated as a suspension or solution.
• Prepared in the form of a powder or granules.

• When the pharmacist dispenses the product, a given quantity

of water is added to constitute the solution or suspension.

94
• Sometimes the amount of water added is varied to obtain
nonstandard doses of the antibiotic as shown in the following
example.

• If a prescription for an amoxycillin product calls for the

addition of 80 ml of water to make 100 ml of constituted
solution containing 125 mg amoxycillin per 5 ml, how should
the instruction be changed to obtain 100 mg amoxycillin per 5
ml?

95
5. 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

96
• The release of the water of crystallization makes the powder
coherent and helps form the granules.

• The effervescence from the release of the carbon dioxide

masks the taste of salty or bitter medications.

97
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.

98
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.

99
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.

100
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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PREPARATION OF POWDERS AND GRANULES

• During the manufacture and extemporaneous preparation of

powders, the general techniques of weighing, measuring,
sifting, and mixing are applied.

• The manually operated procedures usually employed by

pharmacists for preparing powders are
co-milling,
trituration,
pulverization by intervention, and
levigation

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• Trituration, reduce the particle size of powders by grinding
with a mortar and pestle.
• pulverization is also used for reducing the particle size of
solids.
• e.g, camphor, which can’t be pulverized easily by trituration
( sticky properties);
• however, on the addition of a small amount of alcohol or
other volatile solvent, this compound can be reduced readily
to a fine powder because when the solvent is permitted to
evaporate a fine powdered material is formed.

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• Levigation is the process in which a nonsolvent is added to
solid material to form a paste, and particle-size reduction then
is accomplished by rubbing the paste in a mortar with a pestle
or on an ointment slab using a spatula.

• When blending two or more powders the method of

geometric dilution is preferred, especially for unequal
quantities of powders.

• ensures uniformly distribution of small quantities of

ingredients, usually potent drugs

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Steps
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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 COMPOUNDING PHARMACEUTICAL POWDERS

• When working with powders pharmacists should look out for

efflorescent powders
• efflorescent powders include caffeine, citric acid, codeine
phosphate, ferrous sulfate, and atropine sulfate.

• Hygroscopic and deliquescent powders should also be handled

with care since these substances become moist because of their
affinity for moisture in the air. Double wrapping is desirable for
further protection.

• Extremely deliquescent compounds cannot be prepared

satisfactorily as powders.
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 PACKAGING OF POWDERS AND GRANULES

• Oral powders may be dispensed in

 in divided powders wrapped in materials such as bond
paper and parchment, polyethylene envelopes

in bulk
are dispensed in papers, metal foil, small heat-sealed
plastic bags, or other containers

• Hygroscopic and volatile drugs can be protected

using a waxed paper, double-wrapped with a bond paper
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 SIZE CLASSIFICATION OF POWDERS
After preparation powders are classified according to their
particle size.
In order to qualify the particle size of a given powder, the USP
uses the following descriptive terms:
• Very coarse powder: All particles pass through a No. 8 sieve
(2.38 mm) and not more than 20% pass through a No. 60
sieve.
• Coarse powder: All particles pass through a No. 20 sieve (0.84
mm) and not more than 40% pass through a No. 60 sieve.

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• Moderately coarse powder: All particles pass through a No. 40
sieve (0.42 mm) and not more than 40 % pass through a No. 80
sieve.
• Fine powder: All particles pass through a No. 60 sieve (0.25 mm)
and not more than 40% pass through a No. 100 sieve.
• Very fine powder: All particles pass through a No. 80 sieve (0.18
mm). There is no limit to greater fineness.

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