Development and optimization of ketoconazole loaded nano-transfersomal gel for vaginal delivery using Box-Behnken design: In vitro, ex vivo characterization and antimicrobial evaluation

In the present study, Ketoconazole loaded transfersomal formulation was developed using 3-factor, 3-level Box-Behnken design to find out the best formulation. Optimized transfersomal formulation was prepared by solvent evaporation method and evaluated in vitro for vesicle size (126.9 +/- 5.45 nm) and entrapment efficiency (82.6%). Transfersomal gel were developed by incorporation of optimized transfersomal formulation into 1% carbopol gel base and characterized by physical evaluation and rheological studies. The cumulative release of drug were shown at 72 h approximately 74% and 97% of ketoconazole from suspension and transfersomal gels respectively. The flux for transfersomal gel was found to be about 3 times that of drug suspension gel. Results of the histopathological studies of gel treated skin indicated negligible sign of toxicity and irritation. The prepared transfersomal gel showed antimicrobial activity against Candida albicans with MIC 4.57-4.6 mu g/mL and better zone of inhibition as compared to reference standard. The developed gel showed promising antimicrobial activity. These overall findings suggested that transfersomal gel holds an excellent potential for ketoconazole delivery. (c) 2017 Elsevier B.V. All rights reserved.