不同高分子材料及有机溶剂体系对阿司匹林缓释微球的影响

Influences of Polymer Materials and Organic Solvent System on Aspirin Microspheres

目的:采用乳化溶剂挥发法,考察不同种类高分子材料对阿司匹林(Asp)缓释微球(MS)包封率及载药量的影响。方法:采用不同溶剂体系制备Asp缓释MS,通过激光粒度分析仪、扫描电子显微镜(SEM)、差示扫描热分析(DSC)、X射线衍射法(XRD)、核磁共振分析(NMR)、红外光谱分析(FT-IR)及体外释药性能等方法考察不同溶剂体系对MS药剂学性能的影响。结果:以高分子材料聚乙二醇-聚(乳酸-羟基乙酸)嵌段共聚物(PEG-PLGA)制备所得MS具有较高载药量和包封率,溶剂体系二氯甲烷(DCM)∶乙酸乙酯(EA)为1∶1、DCM∶丙酮(ACE)为3∶1,前者制备所得MS载药量约为后者的2倍,包封率分别为(126.26±1.74)%及(97.77±2.83)%,平均粒径分别为(142.4±3.25)μm及(100.9±2.52)μm,SEM观察2种溶剂制备所得MS的表面均光滑圆整;DSC及XRD分析结果表明,2种溶剂制备所得MS并不是药物和载体材料的简单物理混合,所述药物可能以无定形状态分散在载体材料中;NMR及FT-IR研究发现,Asp并未与PEG-PLGA发生结合,2种溶剂制备所得MS的结构一致;2种溶剂制备所得MS体外累计释放95%分别需要168 h及120 h。结论:采用PEG-PLGA成功制备了具有较高载药量和包封率的Asp缓释MS,不同溶剂体系的影响为制备不同要求的MS提供了一定的参考价值。

Objective:To investigate the effects of polymer materials of different kinds on the encapsulation rate and drug load of aspirin sustained-release microspheres(AspMS)with the emulsion-evaporation method.Methods:AspMS were prepared through different organic solvent techniques and their pharmac eutical properties were analyzed by laser particle size analyzer,scanning electron microscopy(SEM),differential scanning calorimetry(DSC),X-ray diffraction(XRD),nuclear magnetic resonance analysis(NMR),fourier transform infrared spectroscopy(FT-IR)and in vitro release.Results:The AspMS prepared with polyethylene glycol-poly(lactic acid-glycolic acid,PEG-PLGA)compared to the others had significantly higher drug load and encapsulation efficiency.The drug load of PEG-PLGA microspheres with dichloromethane(DCM)∶ethyl acetate(EA)mixture(1∶1)was almost the double of DCM∶acetone(ACE)mixture(3∶1),and interestingly,the encapsulation efficiency was(126.26±1.74)%and(97.77±2.83)%,respectively.The mean particle sizes of MS prepared with DCM∶EA or DCM∶ACE were(142.4±3.25)μm and(100.9±2.52)μm,respectively.The MS were not made with simple physical mixture of the two substances.NMR and IR analysis showed that Asp was not combined with PEG-PLGA.In vitro,95%cumulative release of the MS prepared with the two solvents needed 168 h and 120 h respectively.Conclusions:The AspMS can be successfully prepared with PEG-PLGA with high drug load,encapsulation efficiency,and good sustained release.The effect of different solvents on the system provides a certain reference value for the preparation of MS with different requirements.