Formulation evaluation of ketoconazole microemulsion-loaded hydrogel with nigella oil as a penetration enhancer.

Abstract

Onychomycosis is an opportunistic fungal infection often infecting people with compromised immune system. Currently available treatment interventions such as physical, surgical, and chemical-based approaches are successful in treating the condition, however, are painful and nonpatient complaint. Moreover, dermal creams with antifungal agents do not penetrate nail plate as required; hence, there is a necessity of developing a novel formulation with enhanced penetration. The aim of the present research work was to develop ketoconazole microemulsion-loaded hydrogel formulation containing nigella oil as permeation enhancer for the treatment of onychomycosis. Screening of oils, surfactants, and cosurfactants were done based on solubility studies followed by the construction of pseudo-ternary phase diagrams with 2% ketoconazole. The microemulsion was characterized for globule size, zeta potential, viscosity, and thermodynamic stability. Ex-vivo studies were carried out using Franz diffusion cells using porcine skin membrane. The antifungal activity of microemulsion-loaded hydrogel was evaluated using cup plate method using Candida albicans and Aspergillus niger. The optimized microemulsion had a composition of 54.97% Capryol:Nigella (2:1), 36.07% Transcutol:Propylene glycol (2:1), and 7.13% water and was later incorporated into polymeric gel base. The microemulsion-loaded hydrogel exhibited a 10hours sustained release profile as compared to the marketed cream and an enhanced activity against marketed ketoconazole cream and compared with marketed ketoconazole formulation. The thermodynamic stability, sustained drug release with greater permeation, and enhanced activity due to the presence of nigella oil in microemulsion-loaded hydrogel warrant its application as an excellent vehicle for treating fungal infections.