【摘要】 背景:红霉素有效治疗浓度维持时间短,毒副作用较大,有必要将其制成靶向缓释制剂。目的:筛选制备肺靶向红霉素明胶微球的最佳工艺。设计、时间及地点:正交设计对比观察实验,2005-06/12在广东药学院药剂实验室完成。材料:红霉素,明胶。方法:根据乳化缩聚法原理,将适量红霉素分散于明胶溶液中,首先与油相形成W/O型乳剂,再经固化等处理后形成微球。在预试验的基础上,选取影响微球性质较显著的4个因素为考察对象,即明胶的浓度、乳化剂的用量、固化时间和搅拌速度,以平均粒径、载药量、包封率为考察指标,根据L9(34)正交设计试验结果优选出最佳处方工艺条件,通过微球的平均粒径、包封率、载药量等指标的加权求和值来衡量,加权求和值越大,质量越好。主要观察指标:正交设计实验结果,微球的平均粒径、载药量、包封率。结果:红霉素明胶微球最佳实验方案为明胶浓度为15%,乳化剂用量为3.0mL,固化时间为0.5h,搅拌速度为1000r/min。最佳方案制得的红霉素明胶微球形态圆整,且药物确已包裹在微球中,微球的平均粒径为(14.15±0.20)μm,载药量为(5.83±0.38)%,包封率为(65.70±0.56)%。肺靶向微球粒径7～25μm的范围占总数的90.16%以上,最佳工艺条件重现性良好。结论:通过L9(34)正交实验设计获得了制备红霉素明胶微球的最佳工艺技术,所制得的微球符合肺靶向微粒的尺寸要求。更多还原

【Abstract】 BACKGROUND:Erythromycin spreads widely in the body with a short period of effective concentrations and has a lot of adverse effects.Therefore,it is necessary to make erythromycin as targeted medicine.OBJECTIVE:To optimize the preparation conditions of erythromycin gelatin microspheres.DESIGN,TIME AND SETTING:An orthogonal controlled test was performed in the Department of Pharmacy,Guangdong Pharmaceutical University from June to December in 2005.MATERIALS:Erythromycin and gelatin.METHODS:According to the emulsion principle,erythromycin dispersed in the gelatin solution.In the process of preparing microspheres,the gelatin solution and oil should form W/O emulsion and then it turned into spheres by solidification.The formation and quality of microspheres were influenced by four factors,namely the concentration of gelatin,dosage of emulsifier,the solidification time and the speed of mixing.The arithmetic mean diameter of microspheres,the drug loading efficiency and the encapsulation efficiency were targets for the survey in this study on the basis of pretests.The best preparation conditions were optimized in accordance with the results of L9(34)orthogonal tests.The optimized preparation conditions were obtained according to the results of orthogonal tests.MAIN OUTCOME MEASURES:The mean diameter of microspheres,the drug loading efficiency,the encapsulation efficiency,and the orthogonal tests were examined.RESULTS:The optimized preparation conditions of erythromycin gelatin microspheres included 15% gelatin,3.0 mL emulsifier,0.5 hour solidification and mixing at 1 000 r/min.The erythromycin gelatin microspheres were regular in their morphology.Drug was enveloped in microspheres.The average particle size was(14.15±0.20)μm;the drug loading efficiency and the encapsulation efficiency were(5.83±0.38)% and(65.70±0.56)%,respectively.Over 90.16% of the microspheres was in the range of 7-25 μm;The reappearance of pharmaceutical technology was good.CONCLUSION:The optimized preparation conditions of erythromycin gelatin microspheres are obtained using L9(34)orthogonal tests.The microspheres prepared meet the requirement of the size for lung targeting.更多还原