SPG膜乳化法制备PLGA微球

发布时间：2018-06-17 02:15

本文选题：SPG膜乳化 + PLGA　；参考：《广东药学院》2014年硕士论文

【摘要】：本研究主要以PLGA为微球骨架材料，利用较新型的乳化方式—SPG膜乳化法，分别制备了一种脂溶性药物微球即尼莫地平微球，和一种蛋白微球即溶菌酶微球。对制得这两类药物微球进行载药量及体外缓释效果评价，并对微球的其他性质做了初步的评价。在用O/W法制备尼莫地平微球时，首先以微球的外观、载药量及释放行为为指标研究了处方中各个因素对尼莫地平微球性质的影响，通过单因素考察确定了制备尼莫地平微球的处方条件。之后对尼莫地平微球的工艺稳定性、缓释效果进行了考察，最后对微球进行表征。工艺单因素考察结果表明材料的黏度、材料用量对尼莫地平微球的包封率有较大影响，同时也影响着尼莫地平的体外释放。还有SPG膜孔控制着微球的粒径，对尼莫地平体外释放也有一些影响。经单因素考察优化后的工艺所制备出尼莫地平微球的载药量为16.33%，包封率为97.98%，粒径是45.180μm，径距1.523。其体外释放与原料药相比展示出很好的缓释性能，连续40天释放出55%，符合Ritger-peppas动力学缓释方程。DSC结果表明尼莫地平是以无定形的形式被包裹在微球材料中。同时本研究采用W/O/W乳化法制备了溶菌酶PLGA微球，同样对制备过程的处方因素进行考察。结果显示处方因素与尼莫地平微球相同，材料黏度与用量对微球的包封率有较大影响，此外由于是复乳法制备微球，其中内水相的体积与添加剂也对蛋白微球制备有较大影响。在单因素考察中可制得载药量为11.84%、包封率为72.43%的溶菌酶微球，平均粒径为63.89μm。但其体外释放一周仅释放40%左右，之后释放量极少，表现为不完全释放。对溶菌酶微球的DSC表征及红外表征显示，溶菌酶被包裹在微球内部；溶血试验显示配制的溶菌酶微球混悬液无溶血现象；对其体内外降解显示体外降解7周基本无球形，，而组织切片显示6周内体内微球在逐渐降解，且有良好的组织相容性。本研究主要研究利用SPG膜乳化法制备了脂溶性化药微球和蛋白类微球，并对做出的微球的体内、外的性质进行了初步评价，为之后利用SPG膜乳化法制备微球提供了相应的参考。
[Abstract]:In this study, a kind of liposoluble drug microspheres, nimodipine microspheres, and a protein microsphere, lysozyme microspheres, were prepared by a new emulsification method-SPG membrane emulsification method using PLGA as the microsphere skeleton material. The drug loading and in vitro slow-release effect of the two kinds of microspheres were evaluated, and the other properties of the microspheres were also preliminarily evaluated. In the preparation of Nimodipine microspheres by O / W method, the effects of various factors on the properties of nimodipine microspheres were studied based on the appearance, drug loading and release behavior of the microspheres. The preparation conditions of nimodipine microspheres were determined by single factor investigation. Then the process stability and slow release effect of nimodipine microspheres were investigated. Finally, the microspheres were characterized. The results of single-factor investigation showed that the viscosity and the amount of the material had great influence on the encapsulation efficiency of nimodipine microspheres and also affected the release of nimodipine in vitro. The SPG pore also controls the particle size of the microspheres and has some effects on the release of nimodipine in vitro. Nimodipine microspheres were prepared by single factor investigation. The drug loading of Nimodipine microspheres was 16.33, the encapsulation efficiency was 97.98, the diameter was 45.180 渭 m and the diameter distance was 1.523. The in vitro release of Nimodipine showed a good sustained release performance compared with that of the bulk drug. It was released 55 times for 40 days. The results of DSC showed that Nimodipine was encapsulated in the microspheres in an amorphous form according to the Ritger-peppas kinetic slow-release equation .DSC results showed that Nimodipine was encapsulated in the microspheres in an amorphous form. At the same time, the lysozyme PLGA microspheres were prepared by W / O / W emulsification method. The results showed that the prescription factor was the same as that of nimodipine microspheres, and the viscosity and dosage of the materials had a great influence on the encapsulation efficiency of the microspheres. In addition, the volume of the inner water phase and the additive also had a great influence on the preparation of protein microspheres because of the preparation of the microspheres by the composite emulsion method. The lysozyme microspheres with an entrapment efficiency of 72.43% and an average particle size of 63.89 渭 m were prepared by single factor investigation. However, only about 40% of them were released in a week after release in vitro, but only a few of them were released in vitro, showing incomplete release. DSC and IR analysis of lysozyme microspheres showed that lysozyme was encapsulated in the microspheres, hemolysis test showed that there was no hemolysis in the suspension of lysozyme microspheres, and in vitro and in vivo degradation showed that there was basically no sphere in vitro. Tissue sections showed that the microspheres degraded gradually within 6 weeks and had good histocompatibility. In this study, lipid soluble drug microspheres and protein microspheres were prepared by SPG membrane emulsification method. The properties of the microspheres in vivo and in vitro were preliminarily evaluated, which provided a reference for the preparation of microspheres by SPG membrane emulsification method.
【学位授予单位】：广东药学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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