Solid state interaction studies of drug-polymers (II): warfarin-Eudragit E, RL or S resins

Abstract

The interaction between warfarin and Eudragit resins (E, RL and S) has been investigated in physical mixture, ground mixture and cast film by using solid phase diagram, apparent solubility phase diagram, differential scanning calorimetry, infrared spectroscopy and dissolution rate. The solid diagram was constructed for each warfarin-Eudragit system with different weight ratios, but no interaction was found. The solubility of warfarin in acetone increased significantly with Eudragit E concentration, but increased only a little with the Eudragit RL or S concentration. Thus, the molecular interaction between warfarin and Eudragit resin might occur in acetone but the interaction between warfarin and Eudragit E was more pronounced. Several new IR absorption peaks at 1656 (1662), 1601, 1517 (1520, 1519) and 1488 cm −1 appeared in the warfarin-Eudragit E film after evaporation of acetone but not in the warfarin-Eudragit RL or S films, strongly indicating the occurrence of molecular interaction between warfarin and Eudragit E in the solid state. This molecular interaction resulted in the delayed release of warfarin from tablets and the disappearance of the endothermic peak from DSC thermograms. In addition, a new IR absorption peak at 1517 cm −1 was found in the 24-h ground mixture of warfarin and Eudragit E. Although there was no interaction between warfarin and Eudragit RL or S, an amorphous form of warfarin was induced by Eudragit RL after evaporation of acetone.