Design and Development of Topical Nanoformulations for the Treatment of Fungal Diseases

Abstract

newlineIn the present study, SLN and nanocrystals approach were explored for the effective delivery of combination of antifungal agent (imidazole) with corticosteroid. The combination of clotrimazole (CTZ) and betamethasone dipropionate (BMD) was explored for the effective treatment of candidiasis. Two different novel formulations approaches were adopted: lipid based and non-lipid. With non-lipid based approach media milling technique was successfully explored for the formulation of CTZ and BMD nanocrystals. A stable nanocrystal suspension was obtained with Polysorbate 80 as a stabilizer confirmed after seeing of stabilizers for both the drugs). The DSC and PXRD graphs revealed a reduction in the crystallinity of CTZ-API and BMD-API after media milling which was responsible for improved solubility. newlineWith lipid based approach hot homogenization method was used for formulation of CTZ-SLN and BMD-SLN. Both the drugs show highest solubility in Precirol ATO 5 (PCR) among the screened lipids while Polysorbate 80 was used as stabilizer. The developed CTZ-SLN and BMD-SLN were having good entrapment efficiency and desired particle size (between 200-500 nm) which was confirmed using FESEM. newlineThe nanocrystal and SLN suspension of both CTZ and BMD were incorporated into carbopol gel base to obtain a novel nanogel which would ease the process of application at the infection site. The in-vitro release of the developed nanogel based formulations depicted the 24 h of sustained drug release which makes the formulations suitable for once a day application. newlineEx-vivo skin permeation and drug deposition study reveals the potential of developed nanogel formulation for better deposition of drugs in skin layers with least permeation (lt5). The nanogels were studied for antifungal potential in-vitro with microbial study against C. albicans and in-vivo against C. albicans induced candidiasis in Wistar rats. It was observed that developed nanogels showed significant improvement in the infectious condition with almost complete cure occurring a