Optimisation of sample preparation in the particle-size characterization of active pharmaceutical ingredients by laser diffraction

Abstract

The particle size of active pharmaceutical ingredients (API’s) can affect medicinal product processability, manufacturability, and biopharmaceutical characteristics. Thus, it is imperative to monitor mean particle size and particle size distribution to establish particle size supplier specifications. Laser diffraction is currently the dominant method of particle size distribution analysis, since it is a fast and non-destructive technique, which may be applied to an array of particulate systems presented in various physical forms. However, successful particle size measurement depends on the development of appropriate sampling, sample preparation and measurement techniques. Spatulation, a dispersion technique wherein small portions of the API powder are mixed with small portions of the dispersant, and worked in together using a spatula until all of the components are uniformly combined and blended, suffers from operator variability. The objective of this study was therefore to optimise the method of preparation of two API dispersions, by eliminating the need for spatulation.