Quantitative particle analysis based on electron microscopy imaging data

Keywords:
image analysis electron microscopy particle size distribution

Abstract:
In pharmaceutical industry there is a growing tendency to develop less soluble active ingredients (API). In order to assure acceptable in-vivo dissolution and bioavailability, the trend is to use larger specific surface area of the active substance leading to smaller drug particles. Since the shape of a particle can be considered as its size manifestation in three dimensions and since the surface/volume ratio exponentially increases with a smaller size of the particles, for sub-micron and nano-sized particles the characterization of shape becomes increasingly important. Current size measurement techniques generally rely on an indirect measurement of the particle size, and reporting of Particle Size Distribution (PSD) data generally occurs based on the assumption that the particles are spherical. As pharmaceutical actives are typically obtained by crystallization and milling processes, particles are non-spherical and hence there is an interest in characterizing the accurate particle size and shape. In this study we present promising results based on expanding the “seeing is believing” addagium, i.e. scanning electron microscopy images are used for the quantitative PSD analysis of a pharmaceutical sub-micron suspension. The effects of sample preparation, image acquisition conditions and image processing are evaluated.

Nanotech 2008 Conference Program Abstract