Design and Characterization of Voriconazole-Loaded Topical Gel for Localized Antifungal Delivery

Abstract

Voriconazole is a broad-spectrum triazole antifungal with limited aqueous solubility. The present study was designed to formulate and evaluate a voriconazole-loaded topical gel using Carbopol 971P for localized antifungal delivery. Five formulations (F1-F5) were prepared with increasing concentrations of Carbopol 971P and evaluated by preformulation studies, physicochemical testing, in vitro drug release, antifungal activity against Candida albicans, and short-term stability testing. Voriconazole showed solubility values of 0.75 mg/mL in water and 1.27 mg/mL in phosphate-buffered saline pH 6.4, with substantially higher solubility in chloroform, acetone, and ethanol. The melting point was 128°C and the UV absorption maximum was 255 nm. The calibration curve over 0-50 µg/mL was linear (R² = 0.9988). Drug content of the gels ranged from 97.0% to 98.0%, pH from 6.8 to 7.1, reported spreadability from 10.25 to 11.75, and viscosity from 46,685 to 48,942 cP. Increasing Carbopol 971P concentration increased viscosity and reduced spreadability. At 270 min, F1 showed the highest tabulated cumulative drug release (98.846%), followed by F2 (95.741%), F3 (94.11%), F5 (89.439%), and F4 (88.96%). F1 was selected as the optimized formulation and showed a reported antifungal inhibition value of 6.6 against C. albicans, compared with 7.6 for the standard drug and 0 for placebo. After one month, F1 retained 96.5% drug content at 30 ± 2°C/65 ± 5% RH, whereas drug content decreased to 75% at 40 ± 2°C/75 ± 5% RH. The study demonstrates that Carbopol 971P concentration strongly affects the rheological and release characteristics of voriconazole gels, with F1 providing the most favorable overall profile among the formulations tested.