Properties of polymeric drug delivery systems prepared by hot-melt extrusion.

摘要

The purpose of this research project was to investigate the physicochemical and drug release properties of polymeric drug delivery systems prepared by hot-melt extrusion containing either highly water-soluble drugs or a poorly water-soluble drug. The properties of processed materials were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), stability indicating RP-HPLC assay, dissolution studies, scanning electron microscopy (SEM), X-ray diffractometry, electronic torque rheometry, Zeta potential particle size analysis, and helium pycnometry.; Chlorpheniramine maleate (CPM), diltiazem hydrochloride (DTZ), indomethacin (IDM), and the excipients were thermally and chemically stable following hot-melt extrusion. CPM decreased the glass transition temperature (Tg) of EudragitRTM RS PO and exhibited a solid-state plasticization effect. CPM and IDM were in the amorphous state and DTZ was in the crystalline state following hot-melt extrusion processing. Triethyl citrate (TEC) facilitated the hot-melt extrusion process by decreasing the Tg and the melt viscosity of EudragitRTM RS PO. However, the thermal lubricant, glyceryl monostearate (GMS), only decreased the melt viscosity of the Eudragit RTM RS PO. The CPM release rate constant decreased in the order from tablets prepared by direct compression, hot-melt granulation, and hot-melt extrusion. This was due to an increase in the intermolecular binding and entanglement between drug molecules and polymer molecules that occurred during thermal processing. Post-processing thermal treatment of the hot-melt extrudates had a minimal effect on decreasing the drug release rate since the hot-melt extrusion process enhanced the entanglement of the drug and polymer to a greater extent. Drug release rates from both DTZ and CPM hot-melt extrudates increased with an increase in the TEC level in the formulations, while DTZ release from the EudragitRTM RS 30D coated pellets decreased with an increase of TEC in the coating layer. This could be attributed to the fact that a continuous polymeric structure was formed following hot-melt extrusion regardless of the TEC level. However, for the film coated pellets, coalescence of the polymer particles was enhanced with higher levels of TEC. Due to the lower solubility of IDM, no significant difference in drug release was observed in the IDM hot-melt extrudated granules containing 0%, 4%, and 8% TEC.