Eco-Friendly high Drug-Loading microemulsions with Incorporation of Deep eutectic Solvents: Advancing precision with the dual Ouzo effect

Abstract

Deep eutectic solvents (DES) enhance drug solubility but require delivery systems, while the Ouzo effect enables surfactant-free microemulsion formation despite limitations in oil phase ratio. By integrating DES as the oil phase, this study develops a dual Ouzo effect microemulsion system that induces both microemulsions and nanoprecipitations simultaneously. Through detailed analysis of composition diagrams, precise adjustment of the mass ratio of VA64 to propylene glycol enables strict control over particle size from 200 nm to 550 nm. This approach enhanced curcumin’s solubility to 17.11 mg/mL, a 1700-fold increase compared to its water solubility, with excellent stability showing only 22.4 % degradation after 4 h of light exposure (versus 90–95 % in conventional carriers). The system increased the cumulative release amount of curcumin and presented a rapid initial release followed by a sustained release. Compared with traditional Ouzo effect systems, introducing DES significantly increased the oil phase ratio from 0.05 % to 30 % through enhanced molecular interactions and supersaturation. DES composition adjustment enabled microemulsion stabilization without complex processing, achieving optimal stability with a three-phase contact angle of 89.2° (±0.3°), approaching the theoretical ideal value of 90° for interface stability.