Evaluation of Crystallization Kinetics to Achieve Equant-Shaped Crystals from an Acicular Active Pharmaceutical Ingredient

The crystal morphology of active pharmaceutical ingredients (APIs) significantly affects processing properties, and behavior postformulation, impacting substance performance. Despite vast research on crystallization kinetics and morphology, there is still a gap in integrating these aspects for a comprehensive understanding in bulk crystallization of APIs. This study leverages contemporary technology of miniaturized stirred crystallizers to efficiently correlate crystal morphology and kinetics of a specific API, Bitopertin, whose crystal morphology is highly dependent on supersaturation. By linking positive morphological outcomes with crystallization fundamentals, this study aims to enable rational routes to optimize the crystal morphology and the crystallization process of the selected API. This contribution presents a general method with results specific to Bitopertin, yet providing high transferability, feasibility, and robustness to similar substances with significant morphology-supersaturation dependency.