Formulation, Characterization, Optimization, and Evaluation of Bifonazole Microemulsion-based Emulgel for Topical Delivery

A BSTRACT Background: Bifonazole is a poorly water-soluble imidazole antifungal agent whose therapeutic performance in topical therapy is often limited by poor aqueous solubility, inadequate dermal penetration, and suboptimal drug release from conventional formulations. Microemulsion-based gels (emulgels) offer a promising strategy to enhance drug solubilization, stability, and topical delivery. Aim and Objectives: To develop and optimize a bifonazole-loaded microemulsion-based gel (emulgel) with improved drug solubilization, stability, in vitro drug release, and dermal safety compared with a conventional marketed cream. Materials and Methods: Solubility screening was performed to select suitable oil, surfactant, and cosurfactant for microemulsion formulation. Microemulsions were optimized based on oil concentration, surfactant-to-cosurfactant ratio, and thermodynamic stability. The optimized microemulsion was incorporated into Hydroxy Propyl Methyl Cellulose (HPMC) K100M gel at polymer concentrations ranging from 1% to 2%. The prepared emulgels were evaluated for pH, viscosity, spreadability, drug content, in vitro drug diffusion, accelerated stability, and skin irritation. Results: Oleic acid exhibited the highest bifonazole solubility among the oils (60.48 mg/mL), while isopropyl alcohol (80.18 mg/mL) and Tween 80 (56.33 mg/mL) demonstrated superior solubilizing capacity among the cosurfactants and surfactants, respectively. The optimized microemulsion containing Tween 80 and Span 80 (1:1) showed a drug content of 88.24% and achieved 85.10% cumulative drug release after 5 h. Increasing the HPMC concentration from 1% to 2% increased viscosity (28,100–36,500 cP) and decreased spreadability (22.40–12.98 g/cm/s). The optimized emulgel containing 1% HPMC exhibited an 87.36 ± 0.23% cumulative drug release after 5 h, higher than that of the marketed cream (83.76 ± 0.30%). Accelerated stability studies showed less than 5% variation in formulation characteristics, and no signs of erythema or skin irritation were observed. Conclusion: The optimized bifonazole microemulsion-based gel demonstrated enhanced in vitro drug release, desirable rheological characteristics, good physicochemical stability, and excellent dermal tolerability. These findings suggest that the developed emulgel is a promising topical delivery system for improving bifonazole therapy and warrants further in vivo and clinical evaluation.