Abstract
Clotrimazole (CTZ) is an imidazole derivative, widely preferred for the treatment of topical fungal infections. In the present investigation, CTZ loaded solid lipid nanoparticles (SLN) consisting of percirol ATO 5 and polysorbate 80 were successfully developed using high pressure homogenization and optimized with QbD approach to enhance skin penetration and improve its efficacy. The CTZ loaded SLNs were characterized according to average particle size (450 ± 3.45 nm) and PDI (-36.00 mV). The results were in concordance with FESEM images suggesting uniform size and shape. Further, the gelling agent carbopol with its pseudoplastic behavior showed a crucial role in forming homogenous and stable network for imbibing the CTZ-SLN dispersion for effective retention in skin. As examined, in-vitro drug release was sustained up to 24 h while ex-vivo skin retention and drug permeation studies showed the highest accumulation (56.85 ± 5.08 %) and lowest permeation (2.85 ± 0.12 %) with nanogel in comparison to pure drug and Candid® cream. Further, antifungal assessment of nanogel in experimental rats suggested once a day application for 10 days for complete eradication of fungal infection, supported by histopathological analysis. Additionally, the stability of CTZ-SLNs for 6 months at long term and accelerated conditions of storage was ascribed by stability studies. Henceforth, the above-mentioned findings suggest, nanogel loaded with CTZ-SLNs with effective skin retention could be a potential carrier for management of cutaneous fungal infections.