Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties

Abstract

The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.