Self-nanoemulsifying drug delivery system (SNEDDS) with enhanced solubilization of nystatin for treatment of oral candidiasis: Design, optimization, in vitro and in vivo evaluation

摘要

The aim of the present study is to develop and optimize self-nanoemulsifying drug delivery systems (SNEDDSs) to improve the per-oral bioavailability of poorly soluble polyene antifungal drug, nystatin (NYS), and to evaluate its in vitro and in vivo performance. Solubility of NYS was estimated in various vehicles to select proper components combinations. Oleic acid (oil), Tween (R) 20 (Tw20) and Tween (R) 40 (Tw40) (surfactants) as well as dimethyl sulfoxide (DMSO) and propylene glycol (PG) (co-surfactants) were employed to construct pseudo-ternary phase diagrams. Thermodynamic stability, dispersibility and robustness to dilution tests were performed to optimize formulations from phase diagram. Five optimized formulations composed of oleic acid, Tw20 and DMSO or PG at Smix ratios (1:1,2:1 or 3:1) were selected. They were spherical in shape of mean droplet size <100 nm with negatively charged zeta potential <-15 my. The in vitro release profile of NYS-SNEDDSs was found significant in comparison to the plain NYS suspension. In vitro and in vivo evaluations against Candida albicans depicted promoted antifungal efficacy of selected NYS-SNEDDS formulations compared to marketed and plain NYS suspensions. The results indicate that NYS loaded SNEDDS, with enhanced solubilization and nanosizing, has potential to improve the absorption of drug and increase its oral antifungal efficacy. (c) 2016 Elsevier B.V. All rights reserved.