Formulation and evaluation of a dual-drug film-forming topical gel for synergistic antifungal therapy against cutaneous candidiasis.

Cutaneous candidiasis remains a therapeutic challenge owing to limited skin penetration of anti-fungal agents, high recurrence, and increasing resistance to azoles. In this work, a chitosan-based film-forming gel (FFG) was developed incorporating luliconazole (LUL) and carvacrol (CAR) to improve dermal delivery and therapeutic performance. A 3² factorial design was employed to optimize polymer and plasticizer concentrations, with drying time, spreadability, and viscosity as key formulation attributes. The optimized gel exhibited rapid in situ film formation, suitable viscosity, and mechanical resilience. FTIR and DSC confirmed the absence of drug-excipient interactions. In vitro diffusion and ex vivo permeation studies revealed higher drug release, enhanced skin penetration, and greater retention compared with drug suspensions. The synergistic activity of pure LUL and CAR was demonstrated by checkerboard (FICI = 0.5) and well diffusion assays, confirming a fourfold reduction in minimum inhibitory concentrations. Anti-fungal testing of the CAR-LUL gel showed larger inhibition zones than marketed formulations, while time-kill studies validated faster and more sustained fungicidal activity. Safety was confirmed through skin irritation and histopathological evaluations, and stability analysis demonstrated robustness for six months. These findings establish CAR-LUL FFG as a promising topical platform for effective management of resistant Candida infections.