Deep Eutectic Solvents in Active Pharmaceutical Ingredient Development

Deep eutectic solvents (DESs) are liquids formed by mixing two or more solid components, typically hydrogen bond donors and acceptors, resulting in a large decrease in melting point. Since DESs were first reported in 2003, they have attracted growing attention owing to their low cost, tunable physicochemical properties, and potential environmental compatibility. In pharmaceutical sciences, DESs are increasingly being explored as alternative solvents and functional media for active pharmaceutical ingredient (API) development. This review outlines recent advances in the use of DESs in pharmaceutical research, focusing on the solubilization of poorly water-soluble APIs and the formation of multicomponent crystals. DESs can increase API solubility greatly compared with water, in some cases by several orders of magnitude. In addition, DESs can also be used as crystallization media and coformer sources, enabling the preparation of salts and cocrystals without conventional organic solvents. The effects of DES composition, viscosity, and water content on solubility, crystallization behavior, and processability are also discussed. Although challenges, such as high viscosity and separation of products, remain several mitigation strategies including dilution, additive use and solvent recycling have been proposed. Overall, DESs are a promising platform for innovative, sustainable API development.