Physical Pharmacy

Chapter # 03

Physico-Chemical Principles

F. Micromeritics

Department of Pharmacy
The Islamia University of Bahawalpur

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 Micromeritics
TABLE OF CONTENTS
1. INTRODUCTION
2. PARTICLE SIZE AND SIZE DISTRIBUTION
3. RANGE OF PARTICLE SIZES
4. METHODS FOR DETERMINING PARTICLE SIZE
5. MICROMERITICS APPLICATIONS
6. IMPORTANCE OF MICROMERETICS IN PHARMACY

Introduction
• Micromeritics is the study of fundamental and derived properties of individual as well
as a collection of particles and thus can be called the science and technology of small
particles.
• The particle size of a drug can affect its release from dosage forms that are administered
orally, parenterally, rectally and topically.
• 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.

PARTICLE SIZE AND SIZE DISTRIBUTION

Particle Size
In a collection of particles of more than one size, two properties are important, namely.
1. The shape and surface are of the individual particles.
2. The particle size and size distributions (The size range and number or weight of particles).
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.
RANGE OF PARTICLE SIZES
 A guide to range of particle sizes applicable to each method is.

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METHODS FOR DETERMINING PARTICLE SIZE
Many methods available for determining particle size such as optical microscopy, sieving,
sedimentation and particle volume measurement.
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).
1. 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.
 A dilute suspension of the powder whose particle sizes are to be determined is
suspended in a vehicle in which it is insoluble. A drop of the suspension is mounted on
a slide or and observed under a microscope.
 The data may be scientifically represented as a size- frequency distribution curve. From
the data the average particle size as well as distribution is determined.
Advantages and Disadvantages
Advantages:
 Agglomerates (clusters) (clumps) as well as particles of more than one component can
be detected.
Disadvantages:
 Include the fact that the measured diameter represents 2 dimensions only. The method
tends to be slow and tedious since at least 300 to 500 particles should be counted to get
a reliable data.

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2. 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.
 The stack of sieves is mechanically shaken
to promote the passage of the solids.
 The result achieved will depend on the
duration of the agitation and the manner of
the agitation.

Classification of powder on the basis of sieve no:

3. 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 apparatus.
• The apparatus consists of 200 mm graduated cylinder which can hold a 500 ml of
suspension fluid. A stoppered cylindrical vessel of about 5.5 cm internal diameter with

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 a vertical scale graduated from 0 to 20 cm on it. The stopper has an integral 10 ml bulb
pipette fitted with a 2 way stop cock and a side tube for discharging the sample. The
stem of the pipette is made of narrow bore tubing in order to retain as little of sample
as possible.
Advantages and Disadvantages
Advantages:
• The apparatus is inexpensive and the technique
simple
• The results obtained are precise provided the
technique is standardized.
Disadvantages:
• The method is laborious since separate analysis
is required for each point on distribution curve.
• Very small particles cannot be determined
accurately since their settling is unduly
prolonged and is subject to interference due to
convection, diffusion, and Brownian movement.

4. 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

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Micromeritics Applications
1. Release and dissolution
2. Absorption and drug action
3. Physical stability
4. Dose uniformity

1. Release and dissolution

 Particle size and surface area influence the release of a drug from a dosage form.
 Higher surface area allows intimate contact of the drug with the dissolution fluids in
vivo and increases the drug solubility and dissolution.

2. Absorption and drug action

 Particle size and surface area influence the drug absorption and subsequently the
therapeutic action.
 Higher the dissolution, faster the absorption and hence quicker and greater the drug
action.

3. Physical stability
 The particle size in a formulation influences the physical stability of the suspensions
and emulsions.
 Smaller the size of the particle, better the physical stability of the dosage form.

4. Dose uniformity
 Good flow properties of granules and powders are important in the manufacturing of
tablets and capsules
IMPORTANCE OF MICROMERETICS IN PHARMACY
 The physical properties of powders such as bulk density and compressibility are dependent
on the particle size and size distribution.
 The rate of dissolution of poorly soluble drugs is directly related to the size of the drug
particles. In general, a decrease in the particle size of the drug increases the dissolution rate.
 Properties of drugs such as rate of absorption and hence the pharmacological activity
depends on the particle size

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 Elegance of pharmaceutical preparations such as emulsions, suspensions, ointments often
depend upon the particle size of the dispersed phase.
 The release characteristics of drugs from ointments, creams and suppositories are
dependent on the particle size of the dispersed drug.
 Particle size of the dispersed drug also influences the spread ability and performance of
some cosmetic preparations like dusting powders.

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