Ionic Liquids in Pharmaceuticals: A Scoping Review of Formulation Strategies
Igor Luiz Gonçalves Pereira, Ana Luíza Ziulkoski, Κarine Modolon Zepon, Luiz Alberto Kanis, Henri Stephan Schrekker
Abstract
High Resolution Image Download MS PowerPoint Slide Ionic liquids (ILs) have rapidly emerged as multifunctional formulation tools capable of addressing long-standing challenges in drug delivery. This scoping review systematically assessed their pharmaceutical applications through a structured search of Scopus, PubMed, and Web of Science, yielding 1866 records, of which 91 experimental studies met the inclusion criteria. Across oral, injectable, topical, transdermal, nasal, and advanced delivery systems, ILs consistently improved the drug solubility, chemical stability, mucosal permeability, and overall biopharmaceutical performance. Choline- and imidazolium-based ILs were the most frequently investigated, demonstrating favorable safety profiles and significant pharmacokinetic benefits─including increases in maximum plasma concentration ( C max ), area under the concentration–time curve (AUC), and duration of action for poorly soluble small molecules, peptides, and biologics. Beyond classical excipient roles, ILs acted as structural and functional components in next-generation delivery platforms such as self-emulsifying systems, ionogels, microneedles, polymer–IL nanocomposites, and mucoadhesive films. Mechanistic evidence highlights their capacity to modulate molecular solvation, disrupt biological barriers, enable reversible tight-junction opening, and stabilize labile biomacromolecules. Collectively, these findings establish ILs as versatile and tunable design elements capable of overcoming key limitations in drug solubility and bioavailability. However, despite substantial preclinical progress, the clinical translation of IL-based formulations remains limited by regulatory uncertainty and the need for standardized toxicological and environmental safety evaluations.