Application of fats and waxes in combination with ethylcellulose as coating materials for controlled release of diltiazem hydrochloride pellets using fluidized bed technique

Abstract

The high dose (90 mg) of diltiazem hydrochloride pellets with Avicel PH101® and HPC-M ® were prepared by extrusion-spheronization process and found to possess spherical shape, smooth surface and narrow siae distribution. They were coated with organic solvent base solutions of either pure waxes (carnauba wax, glycerly monostearate and Compritol 888 ATO®) or pure ethylcellulose. Therefore, the suitable wax type was selected for next studies. The experiments shown that Comproitol 888 ATO®, one of the interested wax coating material, is the most optimal coating agent. Further studies revealed that the DTZ HCI coated pellets with the mixtures of Compritol 888 ATO® and ethlycellulose (1:1) at 10% weight gain provided drug release profile in accordance with the USP 24 requirement. The interaction of Compritol 888 ATO® and ethylcellulose were evaluated and observed for chemical interaction. Various methods were used such as X-ray Diffractometry, Infrared Spectroscopy, and Differential Scanning Calorimetry. They indicated that only physical mixture was the best answer of the blended materials. The release mechanism of DTZ HCI from coated pellets was found to compose of diffusion of drug through mix films and release through an aqueous channel of coating membrane. The mechanical stress test of the film coated DTZ HCI pellets via polystyrene beads showed resistant of the film under GI stress condition. The in vitro pH change dissolution study of DTZ HCI pellets were conducted and compared with typical dissolution study following the requirement of USP 24 that utilized deionized water as dissolution medium. The studies indicated that the initial period of both normal and pH change (pH 1.2) dissolution test, DTZ HCI was released at equal amount at both condition (P>0.05). Conversely, on the later period of pH change (pH 6.8), the higher drug release was observed (P < 0.05).