Physical Pharmacy

20th Lecture

1st Feb, 2023

MICROMERITICS

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 CONTENTS
1. Particle Size and Size Distribution.

2. Methods for determining particle size.

3. Density and Flow properties of powders.

4. Importance of particle size.

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 Micromeritics
• Definition: It is the science and technology of
small particles.
• The unit of particle size used: micrometer (µm),
micron (µ).
• As particle size decreases , area increases 

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 Micromeritics
• Knowledge and control of the size and the size range
of particles are of significant importance in pharmacy
because the size and surface area of a particle related
to the physical, chemical and pharmacologic
properties of a drug.

• 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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 Micromeritics
• 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.

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 Particle Size and
Size Distribution
In a collection of particles of more than one size,
(In other words in a Polydisperse sample)

Two properties are important, namely.

1. The shape and surface area of the individual

particles.

2. The particle size and size distributions (The size

range and number or weight of particles).
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 Particle Size
The size of a sphere is readily expressed in terms of its
diameter.
•  The Surface diameter (ds) is the diameter of a sphere
having the same surface area as the particle.
• The Volume diameter (dv) is the diameter of
a sphere having the same volume as the particle.
 The Projected diameter (dp) is the projected diameter of a
sphere having the same observed area as the particle when
• viewed normal to its most stable plane.
 The Stokes diameter (dst) is the diameter which describes
• an equivalent sphere undergoing sedimentation at the same
rate as the asymmetric particle. Stokes diameter is
determined from sedimentation studies of suspended
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particles.
 Particle Size Distribution
• Any collection of particles is usually polydisperse.

• 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 the particle-size distribution and from it we can

calculate an average particle size for the sample.
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 Particle Size Distribution
• When the number or weight of particles lying
within a certain size range is plotted against the
size range or mean particle size, a so-called
frequency distribution curve is obtained.

• This is important because it is possible to have two

samples with the same average diameter but
different distributions.

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 Methods for determining
particle size
• Many methods available for determining particle size such
as.

1. Optical microscopy (range: 0.2-100 µm).

2. Sieving (range: 40-9500 µm).

3. Sedimentation (range: 0.08-300 µm).

4. Particle volume measurement (range: 0.5-300 µm). 12

 Range of particle sizes
A guide to range of particle sizes applicable to each
method is
Particle size Method
1 m Electron microscope, ultracentrifuge,
adsorption

1 – 100 m Optical microscope, sedimentation,

coulter counter (is an apparatus for
counting and sizing particles suspended
in electrolytes.)

50 m Sieving

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 Optical microscopy
(range: 0.2-100 µm)

The microscope eyepiece is fitted with a micrometer by

which the size of the particles may be estimated.
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Optical Microscopy (range:0.2-100 µm)
• According to the optical microscopic method, an
emulsion or suspension is mounted on ruled slide
on a mechanical stage.

• The microscope eyepiece is fitted with a

micrometer by which the size of the particles can
be estimated.

• The ordinary microscope used for measurement the

particle-size in the range of 0.2 to about 100 µm.
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 Electron Microscopy
An electron microscope is a dynamic instruments that uses highly
energetic electrons of beam for the determination of very fine scales of
particles (up to 0.2 μm).

It has a higher resolving power (0.3 μm) than an optical microscope that
allows the examination of very small objects.

The clear surface features of biological or any other materials can be

observed under electron microscopy, e.g., histopathological studies,
the shape and size of an organelles, and it is useful in the investigation
of clinical specimens like renal diseases, tumor processes, storage
disorders, and infectious agents.

This method provides numerous advantages such as high

magnification (310,000 and high resolution of 0.3 nm), individual
particle examination, and particle shape measurement. However, this
method is expensive and a trained operator is required.
 Disadvantage of
microscopic method

1. The diameter is obtained from only two

dimensions of the particle.

2. The number of particles that must be counted

(300-500) to obtain a good estimation of the
distribution makes the method somewhat
slow and tedious.
Sieving (range: 40-9500 µm)

• Standard size sieves are

available to cover a wide
range of size.
• These sieves are designed to
sit in a stack so that material
falls through smaller and
smaller meshes until it
reaches a mesh which is too
fine for it to pass through.
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Sieving (range: 40-9500 µm)
• The stack of sieves is
mechanically shaken to promote
the passage of the solids.

• The fraction of the material

between pairs of sieve sizes is
determined by weighing the
residue on each sieve.

• The result achieved will depend

on the duration of the agitation
and the manner of the agitation. 19
 Air-jet Sieving

Air-jet sieving overcomes the problem of the formation of

clumps on the sieve, which is a common problem associated
with the simple sieving method.
In this method, a series of plates are fitted with a reduced
pressure stream of air which blows the particles that creates
the blockage during sieving process.
This method is suitable for particles having size below 40 μm.
The sample is introduced into the sieve and covered with a lid.
Sieves fitted with a powerful vacuum cleaner create a strong
jet of air, which helps to disperse the clogged particles present
on the sieve through the slotted nozzle rotating below the
sieve mesh .
Sedimentation (range: 0.08-300 µm)

• By measuring the
terminal settling velocity
of particles through a
liquid medium in a
gravitational centrifugal
environment using
Andreasen appartus.

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 Sedimentation (range: .08 -300μm):

The sedimentation method is based on the

principle of gravity that deals with the
measurement of the rate of settling of the
particles of powders which are uniformly
dispersed in a fluid.
This method is used for the measurement of
particle size in the range of 1200 μm. In this
method, the particle size is expressed via Stokes
diameter (dst) which is referred to as the
diameter of an equivalent sphere having the
same rate of sedimentation of the irregular
particles.
Sedimentation of particles can be studied by
using Andreasen pipette, balance method, and
hydrometer method.
The Andresen pipette is used to extract precise quantities of
suspension ready for analysis. The Pipette is positioned on the
pipette stand that let the vertical movement to be conveniently
adjusted without disturbing the suspension under test.

Andresen Apparatus
 Method of Analysis
A 1% or 2% suspension introduced in the vessel upto 550
ml mark.

The stoppered vessel is shaken to distribute the particles.

At various time intervals, 10ml samples are withdrawn.

Samples are evaporated and weighed and analyzed

by appropriate means.

The particle diameter is calculated from stoke’s equation.

 Particle volume measurement
(range: 0.5-300 µm)
• In this type of machine the powder is suspended in an
electrolyte solution.

• This suspension is then made to flow through a short

insulated capillary section between two electrodes and the
resistance of the system is measured.

• When a particle passes through the capillary there is a

momentary peak in the resistance, the amplitude of the peak
is proportional to the particle size.

• Counting is done by a computer. 26

Particle volume measurement
(range: 0.5-300 µm)

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 References

1. Text book of Physical Pharmacy By Albert

Martin. Chapter 19 Page 486

2. Text Book of Dosage Form Design Considerations, pp.599-

635

3. Text book of Physical Pharmaceutics by CVS

Subramanyam.