pH-Sensitive Nanoparticles Developed and Optimized Using Factorial Design for Oral Delivery of Gliclazide

Abstract

Gliclazide is an oral hypoglycaemic agent used for the treatment of non-insulin dependent diabetes mellitus T2DM. Gliclazide has low solubility in the stomach and poor oral absorption and bioavailability. The pH-dependent solubility of gliclazide influences the intra- and inter-subject variability. The purpose of this study was to develop, optimize and evaluate pH-sensitive nanoparticles (NPs) based on Eudragit® S100 polymer for oral delivery of gliclazide (GLZ) in an attempt to improve its absorption and bioavailability and to reduce its intra- and inter-subject variability. Nanoprecipitation technique was used for preparation of GLZ NPs. A 33 full factorial design was applied to study the effect of independent variables (polymer concentration, volume of the organic phase and stabilizer’s concentration) on the mean particle size, zeta potential and the incorporation efficiency of GLZ NPs. The developed optimal formulation was evaluated using various methods including X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM), drug dissolution and glucose stimulated insulin section test. The analysis of the results revealed transformation of GLZ from crystalline to unstructured form and the absence of any chemical interactions between GLZ and the polymer. The in vitro drug release was dependent on the dissolution behaviour of the polymer. The glucose-stimulated insulin section test showed that incorporation of GLZ into NPs has potentiated its effect on insulin secretion in β cells in presence of 10\xa0mM glucose. Our study suggests that the optimized NPs have a potential to improve the oral absorption of GLZ.