MICROMERITICS

• The term micromeritics simply

indicates the science of small particles

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• The drug content in a tablet or
capsule dosage form is influenced by
the particle size and the size
distribution

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• The availability of a drug to reach
the general circulation, from tablet,
capsule, and suspension dosage
forms, is very much influenced by the
powder particle size

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• The physical and chemical stability
of a drug is very much influenced by
the particle size

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• The bioavailability of a drug, the
ultimate criterion to evaluate a
dosage form, is very much influenced
by the powder particle size;
particularly, for problematic
hydrophobic drugs.

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• For topical products (talc powder and
other cosmetics), very fine particle
size is absolutely essential.
• For many liquid antacid and anti-
diarrheal suspensions, to be effective
quickly, very small particle size is
desired

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• Micromeritics plays a very important
role in the drug development process, the
use of these drugs by patients, and the
performance of a drug in the body,
particularly from the solid dosage forms
such as tablet and capsules, powders,
topical products, and a liquid dosage
form such as suspension (oral as well as
ophthalmic).

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Particle Size & Size Distribution

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Particle Size

• Particle size of a powder is expressed by

measuring the diameter of the particle;

• the smaller the diameter of the particle, the

smaller is the particle size

• This is based on the assumption that the powder

particles are perfectly spherical

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• The reality, however, is quite different.
• In a given powder sample, the particles possess
different shapes (rod, cubical, spherical, granular,
etc.) and different sizes (1, 5, 8, 15, 20, 25
microns, or mm, etc.)

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• Furthermore, as the size of the particle decreases,
so does the tendency of powder particles to
become more irregularly shaped and this
complicates the measurement of the true particle
size determination.

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• Therefore, different particle shape coefficients
have been derived for different geometries and
various equivalent diameters have been
developed to relate the size of the particle to the
shape.

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 EQUIVALENT SPHERICAL DIAMETERS

• Relates the size of the particle to the diameter of

a sphere having the one of the following as
same a parameter:
• Surface area: surface diameter (d ),
s

• Volume: volume diameter (d ),

V

• Observed area: projected diameter (d ),

p

• Sedimentation rate: Stoke’s diameter (d ).

st

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 Size Distribution
• Any collection of particles is polydisperse (i.e.,
more than one particle size);
• Therefore, the size distribution of the particle
must also be determined to characterize the
powder (drug as well as excipients) and determine
the average particle size.

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16
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AVERAGE PARTICLE SIZE

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AVERAGE PARTICLE SIZE

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• When a number or weight of the particles, within a
certain range, is plotted against the size range or
the mean particle size, a frequency distribution
curve is obtained.
• The next figure represents the ideal frequency
curve for the powder material, which never
happens to the particulate matters we deal with in
the development of the dosage forms.

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A typical plot of normal or Gaussian size frequency
distribution curve

What does normal

distribution mean?

(S. Jambhekar, From Theory and Practice of Contemporary

Pharmaceutics) 21
• From the figures of frequency distribution curves
and the data presented in table it should be
apparent what particle size, in the sample, occurs
most frequently.
This is termed mode.

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 Number distribution and weight distribution

The number distribution implies that data were

collected by using a method that counts the
number of particles and the weight distribution
implies the data were generated by using
weighing technique.

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 A typical frequency distribution plot for
pharmaceutical powders

The number distribution

implies that data were
collected by counting the
number of particles

The weight distribution

implies the data were
collected by weighing
technique

(S. Jambhekar from Theory and Practice of Contemporary Pharmaceutics) 24

 SKEWED/NON-SYMMETRICAL SIZE
DISTRIBUTION
Plot the data as frequency vs. logarithm of
particle diameter, a typical bell shaped curve is
obtained.
This is called as log-normal distribution

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 CONVERSION
Number distribution to weight distribution

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LOG-NORMAL DISTRIBUTION
Plot log of particle size
against cumulative
percent frequency on a
probability scale, a
linear relationship is
obtained
Reference point used in
log of particle size
equivalent to 50% of
the probability scale,
that is 50% size.
This gives geometric
mean diameter (dg)
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LOG-NORMAL DISTRIBUTION
Slope is given by geometric
standard deviation, σg

σg = 84% undersize or 16%

oversize/50% size

OR

σg=50%size/16% undersize
or 84% oversize

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 CONVERSION
Number distribution to weight distribution
Hatch Choate Equations

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 PRACTICE QUESTION
Hatch Choate Equations

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 Particle Number (N)

• This is another important powder property in

micromeritics and it is also related to the particle
size of the powder.
• As the name implies, it is the number of particles
(N) per unit weight (gram) of the powder.

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 Particle Number (N)

Assuming that the particles are spherical, the number of

particles (N) in a unit weight of a powder may be computed
as follow;
p.dvn3
Volume of a single particle = ---------
6
Since mass (m) of a particle = volume x ρ

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Therefore,
p.dv3.N. r
Weight of a single particle = -----------
6
The number of particles per gram is then obtained
from the proportion
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N = ---------
p.dv3.r
From the knowledge of the mean volume diameter
(dvn3) and the true density (r) of the a powder, one
can determine the number of particles.

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PRACTICE QUESTION

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How do we measure the particle size?
By using a suitable method, one needs
to determine the particle size of about
500 particles individually. The
available methods will include the
followings:

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• Microscopic (number method)
• Electron Microscopes (number method)
• Sedimentation (weight method)
• Sieving (weight method)
• Coulter Counter method (surface area method)

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MICROSCOPY (NUMBER METHOD)

ADVANTAGES

 0.2-100µ particles
 Helps detect agglomeration
 Adulteration by any other type of particles

DISADVANTAGES

 Slow and tedious

 Provides no estimation of depth (particle thickness)

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SIEVING

 Method uses a series of sieves calibrated by the National

Bureau of standards

DISADVANTAGES

 Variations: sieve loading, duration and intensity of agitation

 Agitation can cause particle attrition

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SEDIMENTATION RATE

h is the distance of fall in time t, dst is the mean diameter of the

particles based on the velocity of sedimentation, ρs in the density
of the particle and ρ0 that of the dispersion medium, ƞ0 is the
viscosity of the medium

LIMITATIONS

 Applies to only spheres falling freely without any hindrance

 Particles must not be aggregated or clumped together
 Flow of the dispersion medium around the particle must be
streamline/laminar, not turbulent

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SEDIMENTATION RATE

 ANDREASEN APPARATUS

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COULTER COUNTER
(PARTICLE VOLUME MEASUREMENT)

 Principle: When a particle is suspended in a conducting liquid passes

through a small orifice on either side of which are electrodes, a change is
electric resistance occurs.
 Change in resistance is related to the particle volume
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 Can count upto 4000 particles/second