Molecularly pegylated lipid microparticles as a novel sustained-release vaginal delivery system for miconazole nitrate

Abstract

The purpose of this study was to investigate intravaginal drug delivery system based on biocompatible phytolipids [Softisan^® 154 (SF) (hydrogenated palm oil) and super-refined sunseed oil (SO)] and polyethylene glycol (PEG)-4000 for sustained delivery of miconazole nitrate (MN). Lipid matrices (LMs) consisting of optimized 1:9 blend of SO and SF with increasing amounts of PEG-4000 (0, 10, 20, 40 % w/w) were prepared by fusion, characterized by differential scanning calorimetry and employed to formulate MN-loaded solid lipid microparticles (SLMs) by melt-homogenization. In vitro drug permeation of the SLMs was evaluated in simulated vaginal fluid (SVF, pH 4.2). Results of thermal analysis confirmed the amorphous nature of the LMs and also indicated that PEG-4000 was molecularly integrated in non-PEGylated LM yielding more amorphous PEGylated LMs. Drug-loaded PEGylated SLMs based on SO:SF (1:9) and PEG-4000 (40 %w/w) (batch DM) exhibited significantly (p < 0.05) higher in vitro permeation coefficient (1.8022 × 10^-4 cm/min) than commercial topical formulation of MN (Fungusol^® lotion) (1.3765 x 10^-4 cm/min) and pure MN sample (1.1892 x 10^-4 cm/min). The developed formulations could be exploited as alternative sustained release intravaginal delivery platform for miconazole nitrate.

Keywords: Miconazole nitrate, Softisan^® 154, Intravaginal drug delivery, PEGylated solid lipid microparticles, Sustained release, Sunseed oil