Formulation Development and Optimization of a Terbinafine Hydrochloride-Loaded Solid Lipid Nanoparticulate Gel for Enhanced Antifungal Efficacy Against Candida albicans

Terbinafine hydrochloride effectively treats superficial fungal infections, but oral use has side effects, and topical forms show poor penetration and short residence. Solid lipid nanoparticles (SLNs) enhance topical delivery by improving skin absorption, providing sustained drug release, and offering a stable, biocompatible carrier for more effective antifungal therapy. This study aimed to develop and optimize a terbinafine hydrochloride-loaded SLN gel to achieve minimal particle size and polydispersity index (PdI), high entrapment efficiency, and enhanced antifungal activity against Candida albicans. SLNs were prepared using a modified hot-melt emulsification followed by ultrasonication. Excipient selection was guided by solubility screening, and a 3³ full-factorial design was used to optimize lipid content, surfactant concentration, and sonication duration. The optimized SLNs were incorporated into a Carbopol® 974P gel and characterized for particle size, PdI, zeta potential, entrapment efficiency, in-vitro drug release, antifungal efficacy, and stability. The optimized formulation produced SLNs with a particle size of 262 nm, a PDI of 0.3, and an entrapment efficiency of 96.88%. The SLN gel showed sustained drug release (85.3% over 24 h), stronger antifungal activity (28 mm inhibition zone) than a marketed cream (10 mm), and good stability for 60 d under International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use conditions. The developed SLN-based gel formulation of terbinafine hydrochloride demonstrated enhanced antifungal efficacy, controlled drug release, and excellent stability, making it a promising candidate for the topical treatment of fungal infections.