Surface Defects and Crystal Growth of Apremilast Benzoic Acid Cocrystals.

A cocrystallization process of the active pharmaceutical ingredient apremilast with benzoic acid is explored in this work. The aim of the study is to adjust operating conditions during the crystallization to purposefully tune the dissolution properties of the final product. Understanding the cocrystallization is key to obtaining a consistent, high-quality product, as well as tuning other properties such as powder flowability or dissolution properties. It was discovered early in development that the studied cocrystallization process does not follow the common rules of crystallization. Better crystals were obtained at faster cooling rates and worse crystals at slower cooling rates. Interestingly, this can be explained by crystal collisions and a two-phase growth of the crystals. Standard operating conditions were further tested, resulting in different shapes and sizes of the product. Different types of produced crystals were tested in a dissolution apparatus and provided significantly modified dissolution profiles.