Quality by Design-Driven Formulation and Evaluation of an Itraconazole Film-Forming Gel for Enhanced Antifungal Activity

Background: Itraconazole, a broad-spectrum antifungal agent, exhibits poor aqueous solubility and limited skin permeability, restricting its effectiveness in conventional topical formulations. Film-Forming Gels (FFGs) represent a promising strategy for enhancing cutaneous drug delivery by forming a sustained-release reservoir on the skin. Objectives: The study aimed to develop and optimize an itraconazole-based Film-Forming Gel (FFG) for enhanced transdermal drug delivery using a Quality by Design (QbD) approach, targeting improved diffusion, antifungal efficacy, and formulation stability. Materials and Methods: A 3² full factorial design was utilized to evaluate the effects of two independent variables-Eudragit RS PO and Carbopol 940 concentrations-on drug diffusion and viscosity. The formulations were evaluated for pH, viscosity, spreadability, drying time, drug content, in vitro drug diffusion, and antifungal activity using standard protocols. Statistical analysis and formulation optimization were performed using Design Expert® 7.0 software. Results: The optimized formulation, comprising 15% Eudragit RS PO and 4.5% Carbopol 940, achieved 99.03% cumulative drug diffusion with a viscosity of 6368 cp. Regression models confirmed the significance of model terms (p<0.05) for both responses, with high model fit (R²=0.9931 for diffusion and 0.9404 for viscosity). The optimized FFG showed a significantly larger inhibition zone (26.87±0.93 mm) against C. albicans compared to the control (14.59±1.25 mm), with statistical confirmation (p<0.001). Stability studies indicated minimal variation in key parameters over three months, maintaining formulation integrity. Conclusion: The QbD-based development successfully optimized a film-forming gel of itraconazole, demonstrating improved drug diffusion, mechanical properties, and antifungal activity. This formulation offers a promising alternative to conventional topical antifungal therapies and supports further clinical investigation.