Optimization and Characterization of Synergistic Antifungal Agents Loaded Hydrogel Formulations for Enhanced Superficial Mycoses
Megharaj Chowdenahalli Narayanashetty, Shashank Gangaiah, Butchi Raju Akondi, Bhavya Prabhakar, Prakash Goudanavar, Mallamma ThippeswamyIntroduction:
Invasive fungal infections caused by Candida albicans have increased markedly among immunocompromised patients. Conventional topical antifungal therapies are often associated with skin irritation, poor patient compliance, and drug resistance, partly due to alcohol-based solvents. This study aimed to develop and evaluate an alcohol-free dual-drug hydrogel containing ketoconazole (KTC) and clotrimazole (CTZ) to enhance antifungal efficacy through synergistic action.
Methods:
The hydrogel formulation was prepared using a co-solvency approach without alcohol solvents. Optimization was carried out using a Box-Behnken design with carbopol, polyethylene glycol 400, and glycerol as independent variables, and spreadability and drug flux as dependent responses. The optimized formulation was evaluated for pH, viscosity, drug content, spreadability, ex vivo drug diffusion, and skin deposition. Antifungal activity was assessed against Candida albicans using the well-diffusion method.
Results:
The optimized hydrogel demonstrated good spreadability, a near-neutral pH of 7.2, and a viscosity of 46,400 cP. Ex vivo diffusion studies showed a drug flux of 0.0332 μg/cm²/min, higher than commercially available formulations. The dual-drug hydrogel exhibited a maximum zone of inhibition of 25.2 mm against C. albicans, indicating enhanced antifungal activity and reduced potential for drug resistance compared to single-drug formulations.
Discussion:
The enhanced antifungal effect is attributed to the synergistic action of KTC and CTZ combined with the optimized hydrogel matrix, which promoted effective drug diffusion, skin retention, and minimal irritation.
Conclusion:
The developed dual-drug hydrogel represents a promising alcohol-free antifungal delivery system with improved efficacy, safety, and patient compliance.