Particle Size Analysis

• Knowledge and control of the size and the size range, of particles, are of profound importance in pharmacy. Thus, the size, and hence the surface area, of a particle can be related in a significant way to the physical, chemical, and pharmacological properties of a drug.
• Clinically, the particle size of a drug can affect its release from dosage forms that are administered orally, parenterally, rectally, and topically.
• The successful formulation of suspensions, emulsions, and tablets, from the viewpoints of both physical stability and pharmacologic response, also depends on the particle size achieved in the product.
• In the area of tablets and capsules manufacture, control of the particle size is essential in:

1. Achieving the necessary flow properties, and
2. Proper mixing of granules and powders.

Methods of Particle Size Analysis

1. Sieving Method

• This method is the simplest and most widely used method of determining particle size and size distribution.
• Results are obtained on a weight basis.
• It is useful for a practical lower limit of 76 μ.
• This method utilizes a series of standard sieves calibrated by the National Bureau of Standards.
• According to the method of USP, a definite mass of the sample is placed on the proper sieve in a mechanical shaker. The powder is shaken for a definite period of time, and the material that passes through one sieve and is retained on the next finer sieve is collected and weighed.

2. Optical Microscopy Method

• According to this method, an emulsion or suspension is mounted on a slide and placed on a mechanical stage. The microscope eyepiece is fitted with a micrometer by which the size of the particles may be estimated. The field can be projected onto a screen where the particles are measured more easily, or a photograph can be taken from which a slide is prepared and projected on a screen for measurement.

Disadvantages:

• The diameter is obtained only from two dimensions of the particle, length, and breadth. No estimation of the depth (thickness) of the particle is ordinarily available.
• The number of particles that must be counted is from 300 – 500; in order to obtain a good estimation of the distribution, and this makes the method somewhat slow and tedious.

ALSO READ: SOP for Operation of Malvern Particle Size Analyzer

3. Sedimentation Method

• The analysis is carried out in the following manner: A 1 or 2% suspension of the particles in a medium containing a suitable deflocculating agent is introduced into the Andreasen Apparatus. Then, at various time intervals, a sample of the suspension is taken and analyzed.

Methods of Data Presentation

Tables

The most precise and general method of data presentation is the tabular form since the data can be expressed explicitly. The table can be a listing of size versus one of the many ways of expressing their distribution, e.g., size frequency or size accumulation.

Graphs

Histograms:

A histogram is a plot of the frequency of occurrence as a function of the size range. The ordinate, and frequency, can represent the weight, surface area, or any other weighing process, in the specific size interval.

Size Frequency Curve:

This is a smooth curve drawn through the midpoints of the bars of a histogram.

Cumulative Plots:

Cumulative plots can be described as those which involve plotting the percent of particles greater than (or less than) a given particle size against the particle size. Thus, the limiting values of the ordinate vary from 0 to 100%. The ordinate can represent different weighing processes.

Determination of Particle Size by Sieving Method

Objectives

1. To determine the particle size and size distribution using the sieving method.
2. To get acquainted with the different methods of data presentation and interpretation of the results.

Procedure

• Weigh accurately 100g of the sample powder, then place it on the top sieve of the stack of sieves, cover it, and shake it (mechanically) for 15 minutes.
• Weigh the remaining powder on each sieve.
• Tabulate your results.
• Plot the required curves (histogram, normal distribution curve, and cumulative curves).

Table of Results

Sieve Diameter (Particle Size), mm	Mean Particle Size (mm)	Weight Retained on the smaller sieve (g)	% Weight Retained (Frequency)	Cumulative %
				Under-size	Over-size
1.7 - 1.25
1.25 - 0.8
0.8 - 0.6
0.6 - 0.5
0.5 - 0.315
0.315 - 0.25
0.25 - 0.125
		Σ=

• Using graph paper, plot the following curves:

1. Histogram ( frequency vs. p.s. range).
2. Size distribution curve ( frequency vs. mean p.s.).
3. % cumulative curve ( % cumulative vs. mean p.s.).

ALSO READ: SOP for Calibration of Malvern Particle Size Analyzer