Study On Preparation Of PLLA Microspheres And Drug-Releasing Performance

Biodegradable polymeric microspheres, as a new type of controlled drug delivery system, have been widely researched. It has advantages of controlled release of drug molecules, totarget sites, reduce side effect and improve therapeutic effect. But the application of microspheres is restricted because of low encapsulation efficiency and initial burst of drug release.In this dissertation, PLLA microspheres were prepared by the solvent evaporation method, and the results of the research were expanded at the following points:First, the influence factors in the progress of preparing PLLA microspheres were studied according to monofactor method and multifactor orthogonalizing design method. The concentration of PLLA, the concentration of PVA, stirring rate, needle gauge and N₂ velocity could affect microspheres characterize in evidence. The optimum preparation condition was: the PLLA concentration was 5%, the PVA concentration was 0.9%, the stirring rate was 1600r/min, the needle gauge was 0.6 mm, and the N₂ velocity was 1.0m³/h. The microspheres prepared by the optimum preparation method were smooth, regular in morphology, good decentralization, and the average particle size was 20μm with narrow size distribution.Second, we researched the characteristic of Urapidil Hydrochloride-PLLA microspheres. The result showed that the best ratio of Urapidil Hydrochloride and PLLA was 1:2. Two methods were used for increasing drug loading efficiency. One was adding ethanol to inner phase; the other was adding salt to outer phase. The results showed that both of them could increase drug loading efficiency effectively. Third, in vitro release of Urapidil Hydrochloride from microspheres was performed by oscillating in constant temperature. The release study indicated that the Urapidil Hydrochloride-PLLA microspheres exhibited better sustained-release capacity, and the kinetics of Urapidil Hydrochloride-PLLA microspheres in vitro release could be described by Higuchi equation. Coating chitosan, chitosan and sodium alginate(SA) on Urapidil Hydrochloride-PLLA microspheres could effectively improve initical bursts in the early release period. And both of them also could be described by Higuchi equation.