Nano-vesicular delivery system loaded by Bifonazole: Preparation, optimization, and assessment of pharmacokinetic and antifungal activity

Abstract

Bifonazole (BF) is a highly lipophilic antifungal drug that has limited absorption. A self-nano-emulsifying drug delivery system (SNEDDS) not only aids solubility, but it also enhances the absorption. The aim was to formulate BF-SNEDDS for topical delivery using the mixture design and to evaluate the antifungal activity, permeability, and in-vivo pharmacokinetics. Solubility of BF in different oils, surfactants, and cosurfactants was evaluated. A mixture design was used to optimize the formulation variables, X1 (Peceol% as oil), X2 (Kolliphore % as a surfactant), and X3 (Plurol Oleique% as cosurfactant), to evaluate their effects on the globule size. Antifungal activity against Candida albicans, and ex-vivo permeability across rat abdominal membrane were evaluated. The in-vivo pharmacokinetics was also assessed. Results of mixture design indicated that the optimum levels for SNEDDs components were X1(15%), X2(65%), and X3(20%). The globule size, the zone of inhibition, and permeability coefficient for the optimized formula were 36 ± 3 nm, 26 ± 3 mm, and 7.3 × 10−4 cm/min, respectively. This results indicated that, the optimum formula enhances the antifungal activity, ex vivo permeability, and in vivo bioavailability by 1.85-fold, 2.179-fold, and 6-fold, respectively, compared to aqueous suspension. In conclusion, BF-SNEDDS had enhanced anti-fungal pharmacotherapy and acts as a promising medium for transdermal delivery.