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.
Yoncheva
K
K
Faculty of Pharmacy, Medical University, 2 Dunav Street, 1000 Sofia, Bulgaria.
Miloshev
S
S
Belcheva
N
N
Lambov
N
N
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004176:Dipyridamole / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D008293:Malates / Q000008:administration & dosage*; D008863:Microspheres; D010316:Particle Size; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage*; D051381:Rats; D013678:Technology, Pharmaceutical
D003692:Delayed-Action Preparations; D008293:Malates; D010726:Phosphodiesterase Inhibitors; D011108:Polymers; D004176:Dipyridamole; C074640:poly(malate)