Development and Optimization of Zaleplon Loaded Eudragit® Nanoparticles for Oral Delivery: In-Vitro and in-Vivo Evaluation

Abstract

Polymeric nanoparticles (PNPs) have a great potential as drug delivery systems regarding their small size, high physicochemical stability, and sustainedrelease properties. Zaleplon (Za) is a model BCS class II drug with sedative and hypnotic actions. Zaleplon loaded polymeric nanoparticles (Za-NPs) were prepared from Eudragit ® RS100 using a single emulsion solvent evaporation technique. Full factorial design (2 3) was applied to optimize the physicochemical characterization of Za-NPs. The three independent variables were the amount of polymer, the concentration of PVA and the volume of organic phase. The effects of these variables on particle size (PS), zeta potential (ZP), entrapment efficiency (%EE) and in vitro drug release were investigated. In-vivo study was conducted in rats to evaluate the pharmacological effects of the selected Za-NPs formulations. The designed formulations of Za-NPs had a spherical shape with a size range of 146 to 250 nm and a positive zeta potential in the range of 17.7 to 39.3 mv. The % EE of Za-NPs formulations were in the range of 66.3 to 87.6%. Differential thermal analysis (DTA) showed no interaction between Zaleplon and other excipients meanwhile a change in drug crystallinity was observed. Za-NPs showed a significant increase in the sedative effects in vivo compared with the free drug. Stability studies of the selected lyophilized Za-NPs formulations indicated a high stability after 3 months.