Statistical Optimization of Fluconazole - Loaded Vesicular Systems for the Treatmenet of Skin Fungal Infection

Abstract

The aim of the present study is to improve the bioavailability of fluconazole as a topical antifungal drug by developing an optimized formulation of fluconazole vesicular system for enhanced skin delivery. Different fluconazole loaded vesicular systems were prepared and optimized using a 23 full factorial design considering three independent factors at two levels. In this design, three factors were evaluated; phosphatidyl choline (PC): cholesterol molar ratio (XA), amount of drug added (XB) and type of vesicles either liposomes or ethosomes (XC). The particle size of the vesicles, percentage entrapment efficiency (%EE) and the fluconazole release rate through synthetic membrane were chosen as dependent variables. The levels of the independent variables were chosen based on the preliminary experiments. All fluconazole formulations showed particle size ranging from 794.2 to 5425 (µm), the drug entrapment efficiency ranged from 71.25 to 93.75% and the in vitro drug released ranged from 150.87 to 239.58 (µg/hr/cm2). Screening the influence of the studied factors in the factorial design on the responses revealed that the particle size and %EE of liposomes and ethosomes were increased by decreasing both phosphatidyl choline: cholesterol molar ratio and the drug amount. The release rate of fluconazole through synthetic membrane was increased in both liposomes and ethosomes by increasing phosphatidyl choline: cholesterol molar ratio and the drug amount. It was suggested that the optimized formulation (5:1 phosphatidyl choline: cholesterol molar ratio and 100 mg drug amount) was found to have particle size 5389.85μm, entrapment efficiency 99.5324% and release rate of fluconazole through synthetic membrane 119.906 μg/hr/cm2.