论文部分内容阅读
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。
Background: Erythromycin is effective in treating patients with short duration of maintenance and toxic side effects. It is necessary to make it into a targeted sustained-release preparation. Objective: To screen the best technology for preparing lung-targeting erythromycin gelatin microspheres. DESIGN, TIME AND SETTING: Orthogonal Design Comparison Observation Experiment, 2005-06 / 12 was completed at Pharmacy Laboratory, Guangdong Pharmaceutical University. Material: Erythromycin, gelatin. Methods: According to the principle of emulsification polycondensation, the appropriate amount of erythromycin dispersed in gelatin solution, the first with the oil phase to form a W / O emulsion, and then formed after curing and other microspheres. On the basis of the pre-test, four factors influencing microsphere properties were selected as the test objects, that is, the gelatin concentration, the amount of emulsifier, curing time and stirring speed, the average particle size, drug loading, encapsulation efficiency According to L9 (34) orthogonal design test results, the optimal prescription conditions were selected, and the weighted summation of average particle size, entrapment efficiency and drug loading of microspheres was measured. The larger the value, the better the quality. MAIN OUTCOME MEASURES: Orthogonal design test results, average particle size of microspheres, drug loading, encapsulation efficiency. Results: The best experimental scheme of erythromycin gelatin microspheres was gelatin concentration 15%, emulsifier dosage 3.0mL, curing time 0.5h, stirring speed 1000r / min. The best preparation of erythromycin gelatin microspheres round shape, and the drug has indeed wrapped in microspheres, microspheres average particle size (14.15 ± 0.20) μm, drug loading (5.83 ± 0.38)% , Encapsulation efficiency was (65.70 ± 0.56)%. Lung targeting microspheres 7 ~ 25μm diameter range of more than 90.16% of the total, the best reproducibility of the good conditions. CONCLUSION: The best technology for preparation of erythromycin gelatin microspheres was obtained by orthogonal design of L9 (34). The prepared microspheres accords with the size requirements of lung targeting particles.