Design of Experiments: Optimized Terbinafine-loaded Nanosponge Tablets Using Locust Bean Gum and Chitosan for Enhanced Antifungal Therapy

A BSTRACT Background: Candida albicans infections remain a clinical challenge due to limitations in drug delivery and therapeutic efficacy. Terbinafine is a potent antifungal agent, but conventional formulations often show limited skin retention and penetration. Objective: This study aimed to develop and evaluate terbinafine-loaded nanosponge tablets (TUR-NS-T) for improved topical antifungal therapy. Methods: Nanosponges were formulated using the solvent evaporation technique and characterized for particle size, zeta potential, porosity, and drug entrapment efficiency. The optimized nanosponges were compressed into tablets and assessed for precompression parameters (bulk density, tapped density, Carr’s index, Hausner’s ratio) and postcompression attributes (weight, thickness, hardness, friability, and drug assay). In vivo antifungal efficacy was evaluated in a rat skin infection model. Results: The optimized formulation demonstrated a high entrapment efficiency of 83.84%, a zeta potential of −30 mV indicating good stability, and a porosity of 65.87%, suitable for sustained drug release. The tablets exhibited favorable flow and compressibility with a consistent weight (~400 mg), appropriate hardness (~5.5 kg/cm²), friability of 0.752%, and assay of 99.21%, all complying with regulatory standards. In vivo studies showed a significant reduction (P < 0.05) in C. albicans load compared to untreated, placebo, and even commercial Lamisil®-treated groups. Conclusion: TUR-NS-T formulations demonstrated superior drug retention, deeper skin penetration, and sustained antifungal activity, highlighting their potential as an effective alternative to conventional therapies for treating fungal skin infections.