What is the “typical” particle shape of active pharmaceutical ingredients?

Abstract

The literature contains many articles describing the criticality of particle shape to the performance of pharmaceutical powders, however very little data has been published on this important particle property. To address this gap, particle shape data for over a thousand active pharmaceutical ingredients (API) were analyzed to provide an initial answer to the simple question of “What is the typical particle shape of APIs?” All of the data were collected using a contemporary dynamic imaging system with the particles dispersed in a moving air stream. The suitability of the selected instrument platform was verified by comparing calculated and experimental aspect ratio distributions for several particle shape reference materials and good agreement was obtained in all cases. The principal finding of this “big data” analysis is that particles of typical low molecular weight (<500Da) API may be expected to have a median aspect ratio between 0.6 and 0.8. The analysis also reveals that the API particles typically have low surface roughness. When compared to commonly used excipients, the API particles are slightly less equant. Whilst the results of this analysis are limited to a single data source and single measurement technique, they provide a benchmark that can be used to help design improved manufacturing processes and on-line analytical methods for active pharmaceutical ingredients.