MICROMERITICS
MICROMERITICS is the science and technology of small particles. The unit of
particle size used is the micrometer (μm) micron (μ) .The knowledge and control
of the size of particles is very important in pharmacy and materials science. The
size & hence the surface area of a particle can be related to the physical, chemical
& pharmacologic activity of drug.
Application
1. Release & dissolution:
Particle size & 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 & increases the drug solubility & dissolution. The
particle size of dispersed drug in ointment or suppositories also affects its
release characteristics from to the skin or mucous membrane.
2. Absorption & drug action:
Particle size & surface area influence the drug absorption & subsequently
the therapeutic action. Higher the dissolution, faster the absorption & hence
quicker & greater the drug action
3. Physical stability:
The particle size in a formulation influences the physical stability of the
suspensions & emulsions. With optimum size of the particle, better the
physical stability of the dosage form. If optimum partical size not achieved it
may lead to faster sedimentation or creaming.
4. Dose uniformity:
Good flow properties of granules & powders are important in the
manufacturing of tablets & capsules to get dose uniformity.
Fundamental properties
Particle size and particle size distribution
Particle shape
Particle volume
Particle number
Particle surface area
Particle size and particle size distribution
Powders have collection of particles of more than one size and shape. For
symmetric particles like spheres its easy to describe the size in terms of diameter
but most of the powders are not symmetric in their shape, hence the particle size of
asymmetric particles are expressed in terms of equivalent diameter.
Surface diameter (ds):- The diameter of a sphere having the same surface area as
the particle
Volume diameter(dv) :- The diameter of a sphere having the same volume as the
particle
Projected diameter (dp):- The diameter of a sphere having the same observed
area as the particle.
Stokes’diameter(dst) :-An equivalent sphere undergoing sedimentation at the
same rate as the asymmetric particle.
Average Particle Size (edmundson equation)
The general equation for the average particle size:
n = is the number of particles in a size range whose midpoint, d, is one of the
equivalent diameters.
P= is an index related to the size of an individual particle, because d raised to the
power p = 1, p = 2, or p = 3 is an expression of the particle length, surface, or
volume, respectively.
When the frequency index, f, has values of 0, 1, 2, or 3, then the size frequency
distribution is expressed in terms of the total number, length, surface, or volume of
the particles, respectively.
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.
Fig:A frequency distribution curve
FIG:B (Frequency distribution plot of the data)
An alternative method of representing the data is to plot the cumulative percentage
over or under a particular size versus particle size as shown in Fig C (cumulative
frequency plot). This gives a sigmoid curve with the mode being the particle size
of the greatest slope.
Fig C cumulative frequency plot
When the data is plotted as %frequency verses the logarithm a typical bell shaped
curve is frequently obtained. This is shown in the Fig D
Fig D: log normal distribution curve for polydispersed powder
In case of pharmaceutical powder, these systems tend to have an nonsymmetric, or
skewed, distribution of the When the logarithm of the particle size is plotted
against the cumulative percentage on a log probabilty scale, a linear relationship is
observed as shown in Fig E (log probability Plot). Such a linearplot characterize a
log normal distribution curve by means of two parameters,
The slope of the line
A reference point
The reference point used is the logarithm of the particle size equivalent to 50% on
the probabilty scale, that is the 50% size. This is known as the geometric mean
diameter and is given the symbol d g. The slope is given by the geometric standard
deviation, .
Log probability plot data
Methods for determining particle size
1. Microscopy ( Optical Microscopy)
2. Sieve Analysis
3. Sedimentation Method
Optical Microscopy : Used for partical size determination in size range of 0.2-100
micrometre. Atleast 300 -500 Particals must be counted.
Procedure:
1. A dilute suspension of the powder particles whose sizes are to be determined
is prepared in liquid vehicle in which the powder is insoluble.
2. A drop of suspension is mounted on a slide & observed under the
microscope.
3. The Eye piece of the microscope is fitted with the micrometre (which is
calibrated using stage micrometer) so that, particle size can be measured.
4. All the particles observed in the field are counted & measured through the
eye piece.
5. The dat a is represented as size frequency distribution curve.
6. From the data the avg. particle size & size is determined.
7. For ease of counting the particles, the field viewed through microscope can
be projected on screen or photographed & be measured later.
8. Also particles can be counted with electronic scanner to avoid strain of
visual observation for very small particle.
9. An electron microscope or scanning electrone microscope can be used
Diameters
Martin's diameter (M) The length of the line which bisects the particle image.
The lines may be drawn in any direction which must be maintained constant for all
image measurements. •
Feret's diameter (F) is the distance between two tangents on opposite sides of the
particle, parallel to some fixed direction. •
Disadvantage
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
Advantages
1. Able to examine each particle individually has led to microscopy being
considered as an absolute measurement of particle size.
2. Can distinguish aggregates from single particles
