Monitoring the impact of processing on the size and shape of API particles

As the pharmaceutical industry continues to move towards a quality by design (QbD) paradigm, the design and control of active pharmaceutical ingredient (API) particle characteristics, in particular the control of API particle size and habit with respect to the intended process route, is becoming an area of great interest. Achieving target characteristics for any API can be demanding, but for materials prone to attrition, keeping those characteristics constant can be a significant challenge.

Whilst it is readily accepted that during the development of an API, various processing steps can induce attrition, the initial (pre-formulated) API particle properties are often assumed to be directly indicative of the API properties within the final dosage form. The primary reason for making this assumption is the challenges involved with accurately measuring the particle size characteristics of a single component within a multi-component sample.

The Morphologi G3-ID is an image-based particle characterization system with an integrated Raman probe. The system enables the characterization of particles in terms of both size and shape, and with the use of the Raman probe, can sub-classify the components within a blended sample in terms of their chemistry, thus enabling the determination of the actual particle size and shape distributions for individual components.

The aim of the initial study was to assess the impact of typical unit processes on an attrition-prone API, using a Morphologi G3-ID system to track the material characteristics during processing. The study also investigated the role of excipient selection, impact of similar unit processes upon cohesively-aggregated particles and also how the approach was used to determine the source of the observed attrition.