Exploration of Ionic Liquid in Crystal Engineering: Sustainable Development of Pharmaceutical Solid Forms

Abstract

Ionic liquids (ILs) have garnered remarkable attention in pharmaceutical sciences due to their remarkable tunability and exceptional ability to enhance the physicochemical attributes of drug molecules. ILs possess charge ordering due to different ionic compositions, which may affect the crystallization properties due to the electrostatic interactions with solute molecules. These unique characteristics make them valuable tools in crystal engineering, where they play a crucial role in the development of IL-assisted pharmaceutical solid forms (cocrystals, salts, polymorphs, and eutectic mixtures). Additionally, ILs contribute to a more sustainable and environmentally friendly impact than conventional organic solvents. Therefore, the present review focuses on the integration of ILs in crystal engineering and traces the studies employing diverse ILs for the development of solid forms of API. These reports highlight the ability of ILs to influence a variety of supramolecular interactions impacting the crystal packing. Among the reported studies, salts were found to be more predominant than cocrystals due to the inherent ionic nature of ILs. Nevertheless, the potential of ILs to generate novel salts and metastable polymorphs plays a significant role in extending solid-state landscape endeavors. Keywords: Crystal engineering; cocrystal; polymorphs; ionic liquids; sustainable development