Pharmaceutical Cocrystals: A Perspective on Development and Scale-up of Solution Cocrystallization

Pharmaceutical cocrystals represent an emergent class of successful materials designed based on crystal engineering principles, in which the limitations of the extant drugs are addressed. Though the number of newly reported cocrystals is increasing exponentially, the scale-up of the cocrystallization process has not received enough attention. Solution cocrystallization techniques offer scalable processes that can utilize conventional crystallization machinery and process analytical technologies. The presence of multiple components and competing kinetics of the starting materials as well as the cocrystal make the cocrystallization process harder to study and control. This perspective emphasizes the importance of multicomponent phase diagrams for identifying operating regions in solution cocrystallization and discusses the effects of various operating parameters on the process kinetics. It also covers the intermolecular interactions involved in cocrystal development, cocrystallization methods, and quality control in pharmaceuticals. Furthermore, the role of the Design of Experiment and Quality by Design in scaling up the cocrystallization process efficiently is highlighted. A systematic decision tree has been proposed for scaling up the production of promising cocrystals using solution-based techniques, which can effectively address the current challenges in large-scale cocrystal production and help bring these potential materials to the market in the near future.