SOLID-STATE INTERACTION STUDIES OF DRUG-POLYMERS(II) - WARFARIN-EUDRAGIT E-RESIN, RL-RESIN OR S-RESIN

The interaction between warfarin and Eudragit resins (E, RL and S) has been investigated in physical mixture, ground mixture and cast him by using solid phase diagram, apparent solubility phase diagram, differe ntial scanning calorimetry, infrared spectroscopy and dissolution rate . The solid phase diagram was constructed for each warfarin-Eudragit s ystem with different weight ratios, but no interaction was found. The solubility of warfarin in acetone increased significantly with Eudragi t 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 war farin and Eudragit E was more pronounced. Several new IR absorption pe aks 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 film, 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 fr om 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. Al though there was no interaction between warfarin and Eudragit RL or S, an amorphous form of warfarin was induced by Eudragit RL after evapor ation of acetone.