Dihydromyricetin-Loaded In Situ Film-Forming Emulsions: A Eudragit® RS 100-Based Strategy for Controlled Topical Delivery

Background/Objectives: Dihydromyricetin (DHM), a poorly water-soluble flavonoid with potent antioxidant and skin-rejuvenating properties, exhibits limited skin permeation. This study aimed to develop and characterize DHM-loaded in situ film-forming emulsions (FFE) using Eudragit® RS 100 as the film-forming polymer to enhance skin permeation while minimizing systemic absorption. Methods: FFE formulations, comprising a DHM-loaded lipid mixture and a Eudragit® RS 100 polymer solution, were developed using a full-factorial design of experiments varying poloxamer 407 (P407) and octyl cyanoacrylate (O60/20)/N-methyl-2-pyrrolidone (NMP) concentrations to evaluate drying time, elongation at break, water vapor transmission rate (WVTR), and dermal permeation. The optimized formulation was further characterized for physicochemical properties, chemical integrity, drug loading, and release behaviour. Results: All formulations were homogeneous and physically stable over 24 h. Drying time was positively influenced by P407 but negatively by O60/20/NMP; P407 reduced dermal permeation, while O60/20/NMP had a biphasic effect without significantly affecting elongation at break and WVTR. The optimized FFE (0.079%w/w O60/20/NMP, without P407) showed rapid drying (2.68 min), elongation >10%, and self-formed nanoscale emulsion droplets from the lipid mixture. FTIR confirmed component compatibility; XRD revealed DHM conversion from a crystalline to an amorphous state. Compared with a system without lipid, FFE exhibited significantly higher moisture content (p < 0.001), a lower swelling index (p = 0.021), comparable occlusive factor (p = 0.68), and followed Higuchi kinetic release. Conclusions: The optimized FFE demonstrated desirable film-forming properties and physicochemical compatibility, offering an innovative formulation strategy with translational potential for topical industries. However, substitution of NMP is recommended for cosmetic formulations.