Design and Development of Ciclopirox Topical Nanoemulsion Gel for the Treatment of Subungual Onychomycosis

Abstract:

Onychomycosis is the most common infection of nails caused majorly by Trichophyton rubrum and Trichophyton mentagrophytes and minorly by yeasts. Topical delivery of available ciclopirox formulations as nail lacquer, cream, lotion, gel is hindered by the low permeability of human nail plates, and so there is need of repeated dosing for a longer period of time for effective treatment. In the present research work an attempt is made for effective delivery of ciclopirox olamine (CIC) across human nail plates by enahancing the penetration of CIC and retention time in skin layers. For this purpose nanoemulsion gel, composed of oil, surfactant, cosurfactant, and cabopol was developed by aqueous phase titration method and was evaluated for various in-vitro attributes. Oleic acid, tween 80, and PEG 400 were selected as oil, surfactant and co-surfactant respectively. Pseudoternary phase diagrams were plotted to get the range of nanoemulsion area. For the optimization of the formulation Box Benkhem model (RSM) was applied by taking size and zeta potential as dependant variables and formulation components were taken as independent variables. Total 17 formulations were suggested by the model, which were formulated and subjected to thermodynamic stability study and permeation study. Among thermodynamically stable formulation, SF4 had shown lowest permeation across skin (56.672 μg/cm2/h). SF4 formulation was further evaluated for skin retention study by fluorescent microscopy. Fluorescence microscopy studies were done over a period of 6 hrs clearly giving an indication of longer retention capability of the nano-gel formulation, for the desired topical action.

Keywords: Onychomycosis, Nanoemulsion, permeation, fluorescent microscopy. thermodynamic stability