Formulation And Evaluation of Clotrimazole and Beclomethasone Dipropionate Loaded Nanosponge Based Hydrogel for Improved Topical Delivery

Abstract

Fungal infections affect over a billion individuals annually and are often inadequately treated with conventional topical therapies due to poor skin permeation, uncontrolled drug release, and associated side effects. This study aimed to formulate and evaluate a nanosponge-based hydrogel (NSH) loaded with clotrimazole (CT) and beclomethasone dipropionate (BD) for enhanced topical delivery. Nanosponges were prepared using the emulsion solvent evaporation method with ethyl cellulose as the rate-retarding polymer and polyvinyl alcohol as the emulsifier. The formulations were characterized for particle size (256–613 nm), polydispersity index, zeta potential (–14.3 to –35.4 mV), entrapment efficiency (up to 89.2% for CT and 86.4% for BD), production yield, and surface morphology via scanning electron microscopy, which revealed porous, spherical particles. FTIR and DSC studies confirmed drug-polymer compatibility and a shift to an amorphous state. The nanosponges were incorporated into a hydrogel using Carbopol 934, along with propylene glycol, methylparaben, propylparaben, and triethanolamine. The resulting hydrogel was evaluated for pH (5.1–5.4), viscosity, spreadability, physical appearance, and drug content. In vitro drug release studies demonstrated sustained release from optimized formulations (NS4–NS6), achieving 90.85%, 92.16%, and 94.52% release respectively over 12 hours, following the Higuchi model with Fickian diffusion kinetics. The hydrogel exhibited effective antifungal activity against Candida albicans and was confirmed non-irritant via Draize’s skin irritation test on rabbits. Stability studies conducted under ICH guidelines at 4 ± 2°C and room temperature for 90 days showed no significant changes in physical properties or drug content.These findings demonstrate that the developed CT and BD-loaded nanosponge hydrogel is a stable, effective, and patient-compliant system for the sustained topical treatment of fungal infections such as candidiasis.