Particle Analysis and Laser Diffraction for Providing Effective Pharmaceutical Standards

Analytical method development Analytical method validation guidelines Electron microscopy sciences


Laser diffraction analysis

Traditionally, particle size analysis was conducted using sieving and sedimentation. Over the past 2 decades, however, laser diffraction has significantly replaced these traditional methods.

Particle Sizing and Sieving

This method for providing an analysis of particle size is the oldest in use. It continues to be used, however, for measuring relatively large particles of approximately 1 millimeter.

Particle Sizing and Laser Diffraction Analysis

This method of sizing is especially used for particles that range in size from 0.5 to 1000 microns. Basically, when a laser’s light beam is scattered by a group of particles, the angle at which it scatters is inversely proportional to the size of the particle. In other words, the smaller the particle, the larger the angle at which the light scatters.

It is important to note that Dynamic Light Scattering is considered to be the easiest method to use when measuring very small particles. These would include particles that are as small as 0.5 micrometers.

In general, standard laser diffraction equipment can be utilized for particles that range in size from approximately 400 nanometers to a few millimeters. Other techniques can be used in combination with laser diffraction when working with newer equipment. These include conducting measurements of scattering intensities in various directions down to the lower nanometer range.

Steps to Determine Particle Size by Sieving and Laser Diffraction Methods

Particle size analysis can be determined through both sieving and laser diffraction. This includes taking the following steps in sequential order:

  • Sampling of bulk powders
  • Sub-sampling of bulk samples for specimen
  • Specimen preparation or dispersion
  • Instrument set-up and verification
  • Size measurements
  • Data analysis and interpretation
  • Report of size results

Drug Substances and The Importance of Particle Size Specifications

The International Conference on Harmonization guideline Q6A outlines drug substance particle size specifications and when they should be considered. When a drug’s performance is dependent on and critical to the particle size of the substance, this is vital information. When these analytical method validation guidelines are adhered to, it makes a significant difference as to the quality of the substance. Furthermore, these analytical method validation guidelines are also an indicator of whether or not performance standards will be met.

Particle size has an influence on particular material properties. This applies to the following types of substances:

  • Powders
  • Suspensions
  • Emulsions
  • Aerosols

When powder or droplets ranging in size from 2 to 5 micrometers, for example, they are able to penetrate into the lungs deeper than larger sizes due to being a more efficient aerosol delivery system.

Particle size determination, analysis, and testing are all integral to determining the efficacy of a drug substance. An analytical testing laboratory is able to provide these and other services so that analytical method validation guidelines are being met.

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