Formulation and Evaluation of Microemulsion Gel of Efinaconazole

Onychomycosis is a persistent fungal infection of the nail unit, and its topical treatment is often challenging because of the limited permeability of the nail plate. Efinaconazole, a triazole antifungal agent, exhibits limited aqueous solubility, which may affect its formulation and delivery. The present study aimed to formulate, optimize, and evaluate an efinaconazole-loaded microemulsion gel using a design of experiments (DoE) approach for potential topical application in the management of onychomycosis. Solubility and emulsification studies were performed to select suitable formulation components, resulting in the selection of Captex 500 as the oil phase, Cremophor EL as the surfactant, and ethanol as the cosurfactant. A 3² full factorial design was employed to investigate the effects of surfactant–cosurfactant mixture (Smix) concentration and mixing speed on globule size, percentage transmittance, and in vitro drug release. The optimized microemulsion, EM5, exhibited a globule size of 54.1 nm, percentage transmittance of 90.4%, and in vitro drug release of 88.12%. The microemulsion was subsequently incorporated into Carbopol 934P gel at concentrations of 0.5%, 1.0%, and 1.5% w/w. Among the evaluated formulations, EMG2 containing 1.0% w/w Carbopol 934P demonstrated favorable physicochemical characteri.stics, including a pH of 6.89 ± 0.20, spreadability of 23.4 ± 1.1 g·cm/s, viscosity of 5870.90 ± 30.50 cP, and drug content of 99.2 ± 1.1%. Furthermore, EMG2 achieved 95.3% cumulative drug release over 8 hr. The factorial models exhibited high coefficients of determination, indicating a good fit to the experimental data. Overall, the findings demonstrate the feasibility of developing an efinaconazole-loaded microemulsion gel with favorable physicochemical properties and promising in vitro drug release performance.