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

This finding indicates that deep eutecticsolvents (DESs)can be used for cocrystal or salt crystallization on active pharmaceuticalingredients. DESs were used as the mother liquids for crystallizationand environmentally friendly solvents. Notably, five kinds of cocrystalsor salts precipitated in 10 conditions, two of which were identifiedfor the first time in this study. Active pharmaceutical ingredients (APIs) often exhibitphysicochemicalproblems 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 coformeris widely used today. In recent years, green chemistry and sustainabledevelopment goals have been an active area of research, and a productionmethod is required for reducing the use of organic solvents and implementinga low environmental load. In this study, deep eutectic solvents (DESs)were used as the mother liquids for crystallization and environmentallyfriendly solvents. The DESs were made by combining three types ofcholine salts and a coformer compound of malonic acid. Nine modelAPIs were then dissolved in each DES and crystals precipitated fromthe DESs. As a result, five kinds of cocrystals or salts precipitatedin 10 conditions, two of which were identified for the first timein this study. Crystallization by using DESs is a potent alternativefor discovering novel cocrystals or salts with low environmental impact.