DEEP EUTECTIC SOLVENTS AS EMERGING PLATFORMS FOR IMPROVING THE SOLUBILITY OF POORLY WATER-SOLUBLE DRUGS: A COMPREHENSIVE REVIEW

Background: Insufficient aqueous solubility remains one of the most critical obstacles in the formulation and clinical performance of many contemporary drug molecules, particularly those classified under BCS classes II and IV. Traditional solubility enhancement strategies frequently exhibit limitations related to toxicity, formulation instability, and restricted applicability. Purpose: The present review aims to systematically examine the application of deep eutectic solvents (DESs) and therapeutic deep eutectic systems (THEDES) as novel solubilization tools for poorly water-soluble drugs, highlighting their mechanisms of action, formulation advantages, safety considerations, and translational challenges. Methods: An extensive review of the scientific literature was carried out using major electronic databases including PubMed, ScienceDirect, Google Scholar, and ACS Publications. Peer-reviewed studies published up to early 2025 were evaluated with emphasis on pharmaceutical DES design, solubility enhancement performance, physicochemical characterization, and biological evaluation. Results: DESs have demonstrated remarkable capability to enhance drug solubility by modulating hydrogen bonding interactions, solvent polarity, and microstructural organization of drug molecules. Numerous poorly soluble drugs, such as anti-inflammatory agents, anticancer compounds, and phytoconstituents, have shown substantial improvements in solubility and formulation performance when incorporated into DES-based systems. Nonetheless, concerns related to viscosity, toxicity, and regulatory classification persist. Conclusion: Deep eutectic solvents represent a versatile and environmentally benign alternative to conventional solubilization approaches. Although their pharmaceutical potential is evident, further in-depth toxicological, in vivo, and regulatory studies are essential to facilitate their progression from laboratory research to clinical and commercial applications.