Development and characterization of cross-linked poly(malate) microspheres with dipyridamole

Biodegradable cross-linked microspheres containing up to 63 wt.% of the active substance were obtained in a polycondensation process between D,L-malic acid and the tetrahydroxy compound dipyridamole. The in vitro release mechanism from biodegradable cross-linked microspheres has been studied. It was found that dipyridamole was released due to two-step hydrolysis of the ester bonds of the network. Initially, the only product of the hydrolytic degradation was found to be an oligomeric ester fraction with M-w = 1000 Da. The release of the free drug started after 8 days due to a further hydrolysis of the oligomers in solution. It was found that blood plasma enzymes in rats did not affect the hydrolytic processes. Biodegradable poly(malate) microspheres containing an anti-aggregating agent dipyridamole can be considered as a novel drug delivery system for a prolonged period of time implying a future parenteral application. (C) 2001 Elsevier Science B.V. All rights reserved.