Ionic Liquids: New Forms of Active Pharmaceutical Ingredients with Unique, Tunable Properties

This Review aims to summarize advances over the last 15 years in the development of active pharmaceutical ingredient ionic liquids (API-ILs), which make up a prospective game-changing strategy to overcome multiple problems with conventional solid-state drugs, for example, polymorphism. A critical part of the present Review is the collection of API-ILs and deep eutectic solvents (DESs) prepared to date. The Review covers rules for rational design of API-ILs and tools for API-IL formation, syntheses, and characterization. Nomenclature and ionic speciation, and the confusion that these may cause, are highlighted, particularly for speciation in both ILs and DESs of intermediate ionicity. We also highlight in vivo and in vitro pharmaceutical activity studies, with differences in pharmacokinetic/pharmacodynamic depending on ionicity of API-ILs. A brief overview is provided for the ILs used to deliver drugs, and the Review concludes with key prospects and roadblocks in translating API-ILs into pharmaceutical manufacturing.