膜乳化法制备PLGA-PGA载药微球

发布时间：2018-09-17 12:58

【摘要】：目前,生物可降解材料在医药领域的应用越来越广泛,生物可降解高分子有良好的生物相容性与生物降解性,在药物缓释体系中发挥着越来越重要的作用。将药物负载于生物可降解高分子制备的微球上,实现对药物的控制释放。传统工艺制备的微球存在均一性与制备重复性差、包封率低等缺点。本文以膜乳化法与复乳法结合制备粒径均一、包封率高、药物释放可控的生物可降解载药微球。首先,制备了PLGA、PBLG、PLGA-PGA等生物可降解高分子,并通过1H-NMR和FT-IR等测试方法进行了表征。其次,考察了实验条件对膜乳化制备载药微球的影响。本章使用PLGA作为载体材料、牛血清蛋白作为模型药物、选用孔径为2.6μm的SPG膜进行了研究。对初乳稳定性进行了研究,考察了乳化剂用量、有机溶剂的选择对初乳稳定性的影响；对膜乳化过程参数对制备载药微球的影响进行了研究,考察了膜乳化压力、搅拌速度及固化过程中搅拌速度对制备载药微球的影响。根据本章实验内容对膜乳化工艺条件进行了最优化选择,乳化剂用量为20mg、油相中二氯甲烷与甲苯比例为1：2、膜乳化压力为0.014MPa、搅拌速度为180rpm、固化过程中搅拌速度为120rpm。本章另外考察了初乳粒径与内水相添加剂对膜乳化法制备微球的影响,对微球的外貌、包封率及体外释放现象进行了研究。通过实验表明初乳粒径越小,制备的微球表面光滑、粒径均一、包封率高,释放越平稳。在内水相加入0.5%(ω)的PEG可以有效的提高包封率,制备的微球表面更光滑。最后,制备了PLGA、PLGA-PGA等载药微球并对其进行了表征。采用2.6μmSPG膜通过膜乳化法制备的担载BSA的PLGA微球,粒径较为均一,表面光滑,包封率可达到90.1%,50d累计释放达到82.2%。分别选用不同孔径的SPG膜制备了不同粒径的PLGA载药微球并进行了表征,并对膜乳化制备的不同PLGA微球外貌形成原因进行了分析。制备了PLGA-PGA载药微球,该研究为肠道吸收类型药物的口服制剂的制备提供了方法,有很好的市场前景。
[Abstract]:At present, biodegradable materials are more and more widely used in the field of medicine. Biodegradable polymers have good biocompatibility and biodegradability, and play an increasingly important role in drug delivery systems. In this paper, biodegradable microspheres with uniform particle size, high encapsulation efficiency and controllable drug release were prepared by membrane emulsification combined with double emulsion method.
Firstly, biodegradable polymers such as PLGA, PBLG and PLGA-PGA were prepared and characterized by 1H-NMR and FT-IR.
Secondly, the influence of experimental conditions on the preparation of drug-loaded microspheres by membrane emulsification was investigated. In this chapter, PLGA was used as carrier material, BSP was used as model drug, and SPG membrane with pore size of 2.6 micron was used to study the stability of colostrum. The influence of emulsifying process parameters on the preparation of drug-loaded microspheres was studied. The effects of emulsifying pressure, stirring speed and stirring speed on the preparation of drug-loaded microspheres were investigated. According to the experimental contents in this chapter, the optimum technological conditions of membrane emulsification were selected. The dosage of emulsifier was 20 mg, and the ratio of dichloromethane to toluene in oil phase was 1. 2. Membrane emulsification pressure was 0.014 MPa, stirring speed was 180 rpm, stirring speed was 120 RPM during curing. The effects of colostrum particle size and internal water phase additives on the preparation of microspheres by membrane emulsification were investigated. The appearance, entrapment efficiency and in vitro release of microspheres were studied. The surface is smooth, the particle size is uniform, the encapsulation efficiency is high, and the release is more stable. The encapsulation efficiency can be effectively improved by adding 0.5% (_) PEG into the inner water phase, and the surface of the prepared microspheres is smoother.
Finally, PLGA, PLGA-PGA and other drug-loaded microspheres were prepared and characterized. The PLGA microspheres loaded with BSA were prepared by 2.6 micron SPG membrane through membrane emulsification. The particle size was uniform, the surface was smooth, the encapsulation efficiency was 90.1%, and the cumulative release rate was 82.2% after 50 days. The PLGA-PGA microspheres were prepared by membrane emulsification. The study provided a method for preparation of oral preparations of intestinal absorption drugs and had a good market prospect.
【学位授予单位】：长春工业大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：TQ460.1

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