双氯芬酸钠-聚β-环糊精缓释微球的制备、结构表征 - 第三军医大学学报.docVIP

双氯芬酸钠-聚β-环糊精缓释微球的制备及释药性能考察 王晓明，郑丽娴，郑青，谭载友* (广东药学院 药科学院，广州，510006) 摘要目的 以聚β-环糊精缓释微球为原料，制备双氯芬酸钠-聚β-环糊精缓释微球(DFS-β-CDP微球)，优化合成工艺，并对其进行结构表征及释药性能考察。方法 采用L9(34)正交试验设计，以载药率和包封率为评价指标，判断各种因素对实验结果的影响。建立体外分析方法，考察各因素对药物释放的影响。结果 制备DFS-β-CDP微球的最佳工艺条件为：DFS浓度为20％，载药温度45℃，微球与药物质量比为1:1，载药时间24h。DFS-β-CDP微球的体外释放行为符合一级动力学方程，24h累积释放量达88.32%。结论 采用正交实验设计完成了DFS-β-CDP缓释微球的工艺优化，优化后的处方工艺重现性良好，且具有很好的缓释效果。 关键词双氯芬酸钠；聚β-环糊精；缓释微球；体外释放Preparation and in vitro release of DFS-β-CDP Sustained-Release Microspheres WANG Xiao-ming, ZHENG Li-xian, ZHENG Qing, CAO-Lei, TAN Zai-you (School of Pharmacy, Guangdong Pharmaceutical College, Guangzhou 510006，China) Abstract] Objective To optimize synthesis of DFS-β-CDP microspheres(MS), to characterize its structure and evaluate its characteristics of in vitro release. Method The orthogonal test was used to test the effect of various factors on results with carrying drug ratio and entrapment efficiency as evaluating index. In vitro analytical method was established, and influence of each ingredient on the release of DFS. Result The best technological conditions were: DFS%=20%; temperature=45℃; m(β-CDP MS) : m(DFS)=1:1; time=24h. Drug release pattern in vitro was the best described by one-order kinetics, the accumulative release of 24h was 88.32%. Conclusion Synthetic process of DFS-β-CDP MS was optimized, the repeatability of the technology was precise, and it has the characteristic of sustained releasing. [Keywords] Diclofenac Sodium; β-CDP; sustained release microspheres; in vitro release 环糊精聚合物(CDP)是基于环糊精的聚合物，这种聚合物既能保持环糊精包结、缓释、催化和识别的能力，又兼具高聚物的特性，如良好的机械强度、较好的稳定性、环境敏感性、渗透扩散性和化学可调性等[1]。研究表明，CDP可以实现药物的缓释控释，且其增加水难溶性药物的溶解度、溶解速率和提高药物生物利用度的效果比环糊精单体要有效得多[23]。随着高分子科学的发展，环糊精聚合物已成为当今的热点研究方向之一。双氯芬酸钠(又名双氯灭痛Diclofenac Sodium，DFS)为第二代非甾体解热镇痛抗炎药。具有使用剂量小、疗效高、起效快、不良反应少的特点[4]。但其水溶性差，对胃粘膜的刺激性大，半衰期短而需频繁给药等缺点影响其广泛使用[5]。因此，本研究以聚β-环糊精缓释微球为原料，制备双氯芬酸钠-聚β-环糊精缓释微球，优化其制备工艺，并考察其释药特征。旨在降低其对胃粘膜刺激、减少给药次数，为以后进一步制成适宜的剂型提供理论依据。1 仪器与试药 1.1 仪器 UV-1810紫外-可见分光光度计(上海分析仪器厂)，Q600 SDT型热分析仪(美国TAINC公司)，CS501