Biocompatible Choline- and Amino Acid-Based Ionic Liquids: Applications in Pharmaceutical Science

In pharmaceutical development, synthesizing active pharmaceutical ingredients (APIs) for small-molecule and macromolecular compounds has become increasingly challenging. Many APIs under development do not have optimal solubility, membrane permeability, or stability, substantially complicating formulation or rendering it impossible. Ionic liquids (ILs) have attracted attention in the pharmaceutical field because their chemical structures can be tailored. Moreover, ILs have simple preparation processes and afford high solubility and chemical and thermal stability. However, the use of conventional ILs in pharmaceutical development is limited owing to concerns about biocompatibility, toxicity, and environmental impact. Therefore, in response to these challenges, greater focus has been placed on developing biocompatible ILs, in which both the cation and anion are composed of components that are biologically compatible and/or capable of reducing the environmental burden. This review focuses on ILs developed from biologically related components, especially biocompatible ILs derived from choline and amino acids. Furthermore, it discusses their use in pharmaceuticals, such as catalysts for API synthesis, crystallization, improving solubility, enhancement of skin permeation, designing oral formulations, antibacterial agents, and protectants for macromolecules. Additionally, this review explores how converting APIs into ILs with choline or amino acids can improve their physicochemical properties.