Particle Engineering of an Active Pharmaceutical Ingredient for Improved Micromeritic Properties

A range of particle‐engineering techniques were applied to modify unfavorable bulk solid properties of an active pharmaceutical ingredient (API), with the solid‐state form of the compound remaining constant. The compound under investigation has been crystallized as needle‐like particles, which lead to poor powder‐flow properties, ineffective processing, and problematic formulation behavior. The results show that design and optimization of a cooling crystallization procedure as well as application of alternative approaches, i.e., spherical agglomeration, additive‐controlled crystallization, or ultrasonication, can improve the solid‐state properties of the studied compound. The improvements were quantified by measuring bulk density and flowability, and by comparing the jet‐milling behavior. The design and optimization of robust crystal‐habit‐modification procedures can improve the solid‐state properties of an active pharmaceutical ingredient (API). A toolbox of techniques is available to develop or optimize crystallization processes in light of the crystal shape, thereby enabling more efficient processing and subsequent formulation.