Development and Evaluation of an Efinaconazole–Calotropis procera Latex Antifungal Oil-in-Water Microemulsion for Enhanced Transungual Delivery in Onychomycosis

Abstract

Onychomycosis: a chronic fungal infection of the nail that is limited in penetration of topical drugs because of the thick, keratinized nail plate. The goal of the study was to create and assess an oil-in-water (O/W) microemulsion containing efinaconazole and Calotropis procera latex for transungual antifungal delivery. The formulation was developed using olive oil, Tween 80, PEG 400, glycerine, C. procera latex, and efinaconazole and optimized using a ternary phase diagram followed by physicochemical characterization. Formulations F1–F3 were evaluated comparatively, with an appropriate untreated/free-drug/marketed formulation control used where applicable. All experiments were performed, and quantitative data were analysed, with statistical significance defined as p < 0.05. The optimized formulation (F3) exhibited a droplet size of 42.6 ± 3.1 nm, PDI of 0.21 ± 0.04, zeta potential of −18.7 ± 2.3 mV, viscosity of 38.2 ± 1.5 cP, pH of 6.4 ± 0.2, and drug content of 92.3 ± 2.8%. Compared with efinaconazole-containing control formulation(s), incorporation of C. procera latex was associated with a reduction in MIC from 8 to 2 µg/mL against Candida albicans and from 16 to 4 µg/mL against Trichophyton rubrum. Biofilm assays showed approximately 72% and 74% reduction against C. albicans and T. rubrum, respectively. Confocal laser scanning microscopy demonstrated formulation-dependent coumarin-associated fluorescence, with F3 showing approximately 5.70-fold higher fluorescence than F1. The C. procera latex sample exhibited DPPH radical-scavenging activity with an IC₅₀ of 42.55 ± 0.03 µg/mL. In the transungual release study, F3 showed 24.68% cumulative drug release at 420 min and a maximum recorded flux of 1.44 µg/cm²/h. The principal novelty of the study was the development of an O/W microemulsion combining efinaconazole with C. procera latex and the experimental evaluation of its physicochemical properties, antifungal activity, biofilm reduction, nail-associated fluorescence, and drug-release behaviour. These findings demonstrate the experimentally observed performance of F3 across the evaluated formulation and biological endpoints.