Cocrystal or Salt Crystallization for Active Pharmaceutical Ingredients By Using Deep Eutectic Solvents

Active pharmaceutical ingredients (APIs) often exhibit physicochemical problems that one can remedy by various methods (e.g., salt formation, grinding, ordered mixtures, and cocrystal or amorphous formation). Crystallizing salts or cocrystals from solutions of an API and a coformer is widely used today. In recent years, green chemistry and sustainable development goals have been an active area of research, and a production method is required for reducing the use of organic solvents and implementing a low environmental load. In this study, deep eutectic solvents (DESs) were used as the mother liquids for crystallization and environmentally friendly solvents. The DESs were made by combining three types of choline salts and a coformer compound of malonic acid. Nine model APIs were then dissolved in each DES and crystals precipitated from the DESs. As a result, five kinds of cocrystals or salts precipitated in 10 conditions, two of which were identified for the first time in this study. Crystallization by using DESs is a potent alternative for discovering novel cocrystals or salts with low environmental impact.