Eudragit RS 100 microparticles containing 2-hydroxypropyl-beta-cyclodextrin and glutathione: physicochemical characterization, drug release and transport studies

The aim of this study was to encapsulate glutathione (GSH) alone or in combination with hydroxypropyl--cyclodextrin (HP--CD) in Eudragit RS 100 microparticles (MPs), and to evaluate these novel delivery systems for oral administration of the considered tripeptide. The MPs were prepared by an O/O emulsion–solvent evaporation method according to a multilevel experimental design involving the volume of liquid paraffin, the HP--CD amount, and the drug/polymer ratio as independent variables. The effects of these parameters on particle size, entrapment efficiency, and drug release were investigated. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GSH and Eudragit RS 100 polymer and to characterize the physical state of drug within the MPs. The release profiles of GSH from MPs were examined in vitro at pH 1.2, 6.8. and 7.4 using the USP III (BioDis) dissolution apparatus. In general, a slow and zero-order release of GSH from MPs at pH 1.2 occurred, while at higher pH values considerable amounts of glutathione disulfide (i.e., GSSG)were observed. The enzymatic stability and the intestinal permeability of some GSH-containing MPs were assessed by using pepsin, -chymotrypsin, -glutamyl-transpeptidase and everted frog intestinal sac methodology, respectively. The results suggest that GSH-loaded Eudragit RS 100 MPs containing HP--CD represent a new sustained GSH delivery system useful for the oral administration of the examined tripeptide.