Studies On Biodegradable Materials Used In Drug Sustained Release System

Nimodipine is a dihydropyridine calcium channel blocker, which regulatesintracellular calcium level effectively to maintain normal physiological functions. Itdemonstrates a marked specificity for cerebral vessels. Major interests have focusedon its use in the prevention and treatment of the cerebral ischemic lesions thatfrequently occur in patients with subarachnoid haemorrhages as a result of sustainedcerebral vasospasm and the inhibition of transmembrane calcium influx. However,there are several unfavorable characteristics for this drug. Because of its lower watersolubility, oral bioavailability is lower and variable.In this work, the main goal is to prepare Nimodipine PLA microspheres , whichcan not only prolong acting time, decrease the dose but also minimize side effect, then,a series of novel study method are developed for the microspheres.A solvent extraction method was employed to prepare the Nimodipine PLAmicrospheres. The influences in the process of preparing PLA microspheres werestudied according to an orthogonal-design of experiments. The polymeric theconcentration of internal phase, the concentration of dispersing agent, the ratio ofnimodipine: PLA, volume ratio of oil phase to water phase could affect microspheressize, drug encapsulating efficiency and drug content. The optimum preparationmethod is: the PLA concentration is 7.5%, the gelatin concentration is 1.5%, the ratioof nimodipine: PLA is 2:3, the volume ratio of oil phase to water phase is 5:40. Therepeated tests of optimum preparing method proved that its stability is good.The study on stability indicates that when stored at 37℃, the microspheres fusedand aggregated;while stored at 4℃ or room temperature under sealed condition forsix months, surface morphology, drug content and in vitro release of microsphereswere not altered. It possibly related to the glasstransition temperature for PLA.Studies on the release in vitro showed that the release kinetics of nimodipinefrom PLA microspheres could be described by zero-order equation. The release ratewas related to drug content and some factors for preparation.In conclusion, a new Nimodipine-PLA microspheres that can prolonged actingtime and decrease side effects was developed.