INTERACTION BETWEEN DIPYRIDAMOLE AND EUDRAGIT-S

Amorphous solid dispersions of dipyridamole were prepared by the solvent method using Eudragit S and RL as carriers in order to obtain controlled release dosage forms. When Eudragit S was used the release of dipyridamole from the solid dispersion particles was inhibited at low pH, but remarkably improved at neutral or alkaline pH values which correspond to the pH of polymer dissolution. In contrast, the dissolution of the active drug in acidic media was neither slowed down nor delayed when Eudragit RL was used as the carrying polymer. The striking difference between the drug release profiles of the two coprecipitates seemed to be caused by some interaction between Eudragit S and dipyridamole. The mechanism of this interaction was further investigated using various spectroscopic methods (UV, infrared, H-1 and C-13-NMR). The existence of preferential hydrogen bonding between the carboxylic functions of the polymer and some of the nitrogen atoms of dipyridamole was clearly demonstrated.