复乳法制备聚乳酸微球及其体外释药性能的测定

【作者】 冯晓健；

【导师】 卢文庆；

【作者基本信息】 南京师范大学 ， 物理化学， 2008， 硕士

【摘要】 为了延长药物对病灶组织的作用时间,提高药物的疗效,可通过对药物结构进行修饰或将药物制成长效缓释制剂。载药微球是将药物溶解或者分散到高分子材料中,形成的微小球状结构。本论文以可生物降解材料聚乳酸(PLA)为载体,水溶性头孢唑啉钠(CEZ)为模型药物,采用复乳法制备了聚乳酸-头孢唑啉钠载药微球;并对微球的包封率、载药量、形貌特征进行了表征;用紫外-可见分光光度法考察了载药微球的体外释药性能。具体结果如下:1.考察了聚乳酸分子量的大小和体外释药介质对载药微球释药的影响,分别用分子量为10000和25000的聚乳酸制备了载药微球。扫描电镜结果显示微球呈现良好的球形结构,并且表面多孔,对比图片可以看出由分子量较大的聚乳酸制备得到的微球表面空洞较多,这些孔洞为头孢唑啉钠的溶出提供了通道。分子量10000的微球包封率为23.63%,载药量4.27%;分子量25000的微球包封率为34.46%,载药量6%。红外光谱图谱显示微球中有CEZ和PLA两种成分的特征峰。用差热分析法(DTA)分析得知,聚乳酸和模型药物能够有机地结合为一体。紫外分光光度法对不同分子量的载药微球进行体外释药实验,释药介质分别为PBS(pH=7.3)和胃液(pH=1.2),累积释药曲线表明,在同种释药介质中,分子量大的聚乳酸载药微球释放头孢唑啉钠的速度较慢;而相同分子量的载药微球在PBS(pH=7.3)中的释药速度较快。2.在复乳法的基础上,研究了渗透压在制备微球过程中对微球形貌、包封率、突释效应和释药性能的影响。当内外水相不存在平衡渗透压时,制备的微球具有较高的包封率和载药量,扫描电镜图片显示微球表面光滑无孔;但是随着向内水相加入不同浓度的缓冲溶液时,这时引起了内外水相的渗透压差,导致外水相的水溶液流入内水相,一部分头孢唑啉钠流入外水相;因此制备得到的微球表面多孔,且包封率较低;体外释药曲线显示,表面多空的载药微球具有明显的突释效应,此后是缓慢释放阶段。因此,可以通过改变微球的结构来控制头孢唑啉钠的释放。更多还原

【Abstract】 In order to prolong the action time of the medicine on lesions tissue and improve the effect of the medicine, the drug can be modified structure or be made to long-acting sustained release preparation. Drug carried microspheres made drug dissolve or disperse into polymer materials, forming microspherical structure. In this thesis, polylactic acid-microspheres containing cefamezin were prepared by a W/O/W multiple emulsion solvent evaporation method. The resulted microspheres were characterized with respect to encapsulation efficiency, drug loading, and morphological characteristics. The drug releasing properties of microspheres in vitro were researched by UV-Vis absorption spectrophotometric methods.1. The effects of molecular weight of PLA and drug release medium on the drug-releasing performance of the PLA microspheres were investigated. PLA-CEZ microspheres were prepared by using molecular weight of 10000 and 25000 of polylactic acid. SEM images indicated that the micropheres had a porous structure, and PLA-CEZ microspheres prepared by high molecular weight of PLA were porous, which provided channels of the CEZ from PLA-CEZ. The encapsulation efficiencies were 23.63% and 34.46%, the drug loading were 4.27% and 6%, respectively. It was proved that PLA-CEZ contained the characteristic peaks of cefamezin and polylactic acid by FT-IR. The thermal behavior by differential thermal analysis indicated cefamezin and PLA mingled each other. The releasing behavior of microspheres prepared by different molecular weight of PLA was studied by UV-Vis in PBS and gastric juice. The cumulative release demonstrated that PLA-CEZ prepared by high molecular weight of PLA had a slow-release behavior in the same drug release medium, PLA-CEZ prepared by the same molecular weight of PLA release more quickly in PBS.2. Based on W/O/W multiple emulsion, the effect of osmotic pressure difference between inner water phase and outer water phase on morphological characteristics encapsulation efficiency, burst release and the drug releasing property was studied. When there is no osmotic pressure difference between inner phase and outer phase, the microspheres were smooth and compact with few pores, high encapsulation efficiency and drug loading. Different concentrations of buffer solution addition to the internal aqueous phase create the different osmotic pressure between the inner and outer water phase. Because of osmotic pressure, CEZ was lost into the outer water phase resulted from influx of water from the outer phas, the microspheres was more pores and encapsulation efficiency was low. The drug release from microspheres having many pores on its surface consisted of burst release phase followde by a slow release phase. The CEZ release from the micropheres could be controlled through changes in the structure of the microspheres.更多还原