Crystallization process development

In the manufacture of active pharmaceutical ingredients (APIs), crystallization is a key unit operation. The importance of designing the solid state and particle form of a given API is well-appreciated in the industry as it can impact the downstream processability of the isolated material and can be used to maximise the efficacy of the final drug.

Crystallization provides the first-choice opportunity to achieve this designed particle, however, historically time and cost pressures have inhibited developing the understanding required for robust and reliable processes at an early stage. Consequently, issues such as oiling out, solvent and impurity entrapment, multimodal particle size distributions and previously unseen polymorph transitions have been all too common to first be seen upon process scale-up, often requiring significant quantities of additional time and investment to circumvent.