Influence of thermal processing on the properties of chlorpheniramine maleate tablets containing an acrylic polymer.

The purpose of this investigation was to determine the effects of thermal processing and post-processing thermal treatment on the release properties of chlorpheniramine maleate (CPM) from matrix tablets containing Eudragit RS PO and triethyl citrate (TEC). CPM tablets containing Eudragit RS PO with and without TEC were prepared by direct compression (DC), high shear hot-melt granulation (HMG), and hot-melt extrusion (HME). X-ray diffraction patterns showed that the CPM was distributed in Eudragit RS PO at the molecular level following HME. The thermogravimetry analysis (TGA) profiles of CPM, Eudragit RS PO, and TEC demonstrated that these materials were thermally stable during both the high shear HMG and HME processes. The tablets were subjected to post-processing thermal treatment by storing the tablets at 60 degrees C in open containers for 24 hr. Tablets prepared by DC showed the highest drug release rate constant of 36.2% hr-1/2. When 4% TEC was incorporated into the formulation, the drug release rate constant for the directly compressed tablets decreased to 32.4% hr-1/2. After high shear HMG and HME of the powder blend containing 4% TEC, the drug release rate constant decreased to 30.8 and 13.8% hr-1/2 for the respective processes. The drug release rate constants for all tablets decreased following post-processing thermal treatment. The reduction in release rate 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 the drug release rate since the HME process enhanced the drug and polymer entanglement to a greater extent.