Impact of Mixed Solvent on Co-Crystal Solubility, Ternary Phase Diagram, and Crystallization Scale Up

This contribution covers the identification, understanding, and rationale of the interplay between the choice of mixed solvent on the crystallization of the co-crystal system benzoic acid and isonicotinamide (BZ:INA). A critical first step was gauging the impact of solvent choice and composition on the overall crystallization process, across a number of temperature points. This required defining the solubility and phase diagrams of the co-crystal system at specified temperatures, which reflects the cooling crystallization profile encountered in a batch crystallization step. To this end, identifying and understanding the impact of solvent composition over a selected temperature range on the solubility of co-crystal underpins this contribution.