Microemulsion-based antifungal gel delivery to nail for the treatment of onychomycosis: formulation, optimization, and efficacy studies

Onychomycosis is the most common nail disease affecting nail plate and nail bed. Onychomycosis causes onycholysis which creates cavity between the nail plate and nail bed, where drug formulations could be applied, providing a direct contact of drug with the nail bed facilitating drug delivery on the infected area. The purpose of the present study was to design and evaluate the potential of microemulsion-based gel as colloidal carrier for itraconazole for delivery into onycholytic nails for effective treatment of onychomycosis. Itraconazole-loaded microemulsions were prepared and optimized using D-optimal design. The microemulsion containing 6.24 % oil, 36 % Smix, and 57.76 % water was selected as the optimized batch (MEI). The globule size and drug loading of the optimized batch were 48.2 nm and 12.13 mg/ml, respectively. Diffused reflectance FTIR studies were performed to study drug–excipient incompatibility. Ex vivo permeation studies were carried out using bovine hoof and human cadaver skin as models for nail plate and nail bed, respectively. Microemulsion-based itraconazole gel (MBGI) showed better penetration and retention in human skin as well as bovine hoof as compared to commercial preparation (market formulation, MFI). The cumulative amount of itraconazole permeated from the MBGI after 12 h was 73.39 ± 3.55 μg cm−2which was 1.8 times more than MF. MBGI showed significantly higher ex vivo antifungal activity (P < 0.05) against Candida albicansand Trichophyton rubrumwhen compared to MFI. Stability studies showed that MBGI was stable at refrigeration and room temperature for 3 months. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.Onychomycosis is the most common nail disease affecting nail plate and nail bed. Onychomycosis causes onycholysis which creates cavity between the nail plate and nail bed, where drug formulations could be applied, providing a direct contact of drug with the nail bed facilitating drug delivery on the infected area. The purpose of the present study was to design and evaluate the potential of microemulsion-based gel as colloidal carrier for itraconazole for delivery into onycholytic nails for effective treatment of onychomycosis. Itraconazole-loaded microemulsions were prepared and optimized using D-optimal design. The microemulsion containing 6.24 % oil, 36 % Smix, and 57.76 % water was selected as the optimized batch (MEI). The globule size and drug loading of the optimized batch were 48.2 nm and 12.13 mg/ml, respectively. Diffused reflectance FTIR studies were performed to study drug–excipient incompatibility. Ex vivo permeation studies were carried out using bovine hoof and human cadaver skin as models for nail plate and nail bed, respectively. Microemulsion-based itraconazole gel (MBGI) showed better penetration and retention in human skin as well as bovine hoof as compared to commercial preparation (market formulation, MFI). The cumulative amount of itraconazole permeated from the MBGI after 12 h was 73.39 ± 3.55 μg cm−2which was 1.8 times more than MF. MBGI showed significantly higher ex vivo antifungal activity (P < 0.05) against Candida albicansand Trichophyton rubrumwhen compared to MFI. Stability studies showed that MBGI was stable at refrigeration and room temperature for 3 months. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.