Study On Preparation Of Sustained Release PLGA Microspheres By Novel Membrane Emulsification Technique

Biodegradable polyester is widely used in encapsulating polypeptide, protein and hormone drugs, to achieve long acting sustained release effect. The objective of this thesis is to develop a drugdelivery system of poly(lactic-co-glycolic acid)(PLGA) microspheres. By choosing Premix membrane emulsification and direct membrane emulsification, the desired constant release time of the drugscan be obtained.The exenaitde-PLGA microspheres were prepared by combining direct membrane emulsification technique with double emulsion method, which the release time was longer than two months. It was found that the PVA concentration,stirring rate, the transmembrane pressure played important role on the size distribution of the microspheres. By adjusting the concentration of Na Cl in external water phase and the concentrationof Arlacel 83 the drug encapsulation efficiency was largely increased. After that, we further investigated the effects of particle sizes of drug-loading microspheres and primary emulsion preparation methodson drug encapsulation efficiency and release profiles. In addition, drug encapsulation efficiency was higher, the initial release was lower and cumulative release appearedto be more stable when primary emulsion was made by ultrasonication. By optimizing the process parameters, the drug encapsulation efficiency of microcapsules could exceed 90%. We also investigated the effect of drug-loading efficiency on drug release behavior anddrug bioactivity. It was found that the high drug-loading efficiency microsphere acylation degree was not as much as the low one. Finally, the microclimate p H variables inside the degrading PLGA microspheres offered a good way to explain the principle of the acylation disparity in different drug loaded efficiency microspheres. It turned out that, the acid basic capacity of the bio-drug and the p H of in vitro release environment became powerful to influence the bioactivity preservation.Based on the character of the Thymalfasin, we combine dpremix membrane emulsification technique with solvent evaporation method to prepare Thymalfasin-PLGA microspheres. After that we investigated the effects of several process parameters on the drug encapsulation efficiency and size distribution of the microspheres, including the concentration of PLGA in oil phase, the concentration of oil emulsifier(Arlacel83), p H of external water phase and internal water volume. After optimization, we obtained thymalfasin loaded PLGA microspheres with narrow size distribution(Span value under 0.7), high drug encapsulation efficiency(above 80%), low initial burst release(below 20% in initial 24 h) and constant release rate during 30 d.In conclusion, the PLGA drug-loading microspheres prepared by membrane emulsification technique combined with W/O/W double emulsion method have a potential as sustained release drug delivery system. The direct membrane emulsification technique and premix membrane emulsification techniquemight be applied to prepare different polypeptide and protein drugs- loading microspheres.