周雪,肖潮达,贺智勇,姜丰,吴林菁,肖婷,沈祥春,陶玲
ZHOU Xue,XIAO Chaoda,HE Zhiyong,JIANG Feng,WU Linjing,XIAO Ting,SHEN Xiangchun,TAO Ling

• 1:贵州医科大学贵州省天然药物资源高效利用工程中心贵州省高等学校天然药物药理与成药性评价特色重点实验室贵州医科大学-贵阳市联合重点实验室天然药物资源优效利用重点实验室药学院

摘要(Abstract)：

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 pharmaceutical 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.

关键词(KeyWords)： 阿司匹林;微球;聚乙二醇-聚嵌段共聚物;溶剂体系;乳化溶剂挥发法
aspirin;microspheres;polyethylene glycol-poly;organic solvent system;emulsion solvent evaporation method

Abstract:

Keywords:

基金项目(Foundation): 贵州省科技支撑计划项目[黔科合支撑(2017)2890];; 贵州省科技创新团队项目[黔科合人才团队(2015)4025];; 贵州省高层次创新型人才百层次人才项目[黔科合人才(2015)4029];; 贵州医科大学药学国际科技合作基地[黔科合平台人才(2017)5802]

作者(Author): 周雪,肖潮达,贺智勇,姜丰,吴林菁,肖婷,沈祥春,陶玲
ZHOU Xue,XIAO Chaoda,HE Zhiyong,JIANG Feng,WU Linjing,XIAO Ting,SHEN Xiangchun,TAO Ling

DOI: 10.19367/j.cnki.1000-2707.2019.11.009

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