包埋法制备替米考星淀粉微球工艺的优化
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摘要
[目的]研究替米考星淀粉微球的制备工艺。[方法]以可溶性淀粉为原料,以N,N’-亚甲基双丙烯酰胺为交联剂,以过硫酸钾和亚硫酸氢钠为引发剂,采用包埋法制备替米考星淀粉微球。以载药量和包封率为指标,通过正交试验,采用综合平衡法对替米考星淀粉微球的制备工艺进行优化,在扫描电子显微镜下观察替米考星交联微球的形貌及表面形态。[结果]替米考星淀粉微球的最佳制备工艺如下:替米考星0.02 g,可溶性淀粉4 g,交联剂(N,N’-亚甲基双丙烯酰胺)0.95 g,乳化剂(m_(Span80):m_(Tween80)=2∶1)0.75 g,反应时间1.5 h,在优化工艺参数下制得的替米考星淀粉微球载药量为1.63%,包封率为81.4%;微球大小分布均匀,外观圆整,表面粗糙多孔。[结论]该制备工艺可行,扩大了替米考星的应用,为替米考星的剂型改进提供了参考。
[Objective] To study the preparation process of tilmicosin starch microspheres.[Method] With soluble starch as materials,N,N'-methylene-bis-acrylamide as cross-linking agent and potassium persulfate with sodiun bisulflte as initiator,tilmicosin starch microsphere was synthesized by using embedding method.The preparation process of tilmicosin starch microsphere was optimized by integrated balance method through the orthogonal experiment,with the drug loading and encapsulation rate as indicators.The morphology features and surface topography of tilmicosin starch microsphere were characterized by Quanta 250 FEG scanning electron microscope.[Result]The optimum preparation process was as follows:the quantity of tilmicosin 0.02 g,soluble starch 4.0 g,N,N'-methylene-bis-acrylamide 0.95 g,surfactant(m_(Span80)∶m_(Tween80)=2∶1)0.75 g, and the reaction time was 1.5 h.Under these optimized technology parameters,the drug loading and embedding ratio of tilmicosin starch microsphere were 1.63% and 81.4% respectively.The size of microspheres was uniform,the appearance was round and the surface was rough and porous.[Conclusion] The preparation process was feasible,which expanded the application of tilmicosin.Therefore this research provided references for the improvement of tilmicosin's dosage forms.
[Objective] To study the preparation process of tilmicosin starch microspheres.[Method] With soluble starch as materials,N,N'-methylene-bis-acrylamide as cross-linking agent and potassium persulfate with sodiun bisulflte as initiator,tilmicosin starch microsphere was synthesized by using embedding method.The preparation process of tilmicosin starch microsphere was optimized by integrated balance method through the orthogonal experiment,with the drug loading and encapsulation rate as indicators.The morphology features and surface topography of tilmicosin starch microsphere were characterized by Quanta 250 FEG scanning electron microscope.[Result]The optimum preparation process was as follows:the quantity of tilmicosin 0.02 g,soluble starch 4.0 g,N,N'-methylene-bis-acrylamide 0.95 g,surfactant(m_(Span80)∶m_(Tween80)=2∶1)0.75 g, and the reaction time was 1.5 h.Under these optimized technology parameters,the drug loading and embedding ratio of tilmicosin starch microsphere were 1.63% and 81.4% respectively.The size of microspheres was uniform,the appearance was round and the surface was rough and porous.[Conclusion] The preparation process was feasible,which expanded the application of tilmicosin.Therefore this research provided references for the improvement of tilmicosin's dosage forms.
引文
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[4] 远立国,鲍杰,李成明,等.替米考星肺靶向微球的研制[J].中国兽医科学,2008,38(12):1093-1097.
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[8] PERESWETOFF-MORATH L.Microspheres as nasal drug delivery systems[J].Advanced drug delivery reviews,1998,29(1):185-194.
[9] 李仲谨,杨威,刘艳,等.替米考星淀粉微球的制备及缓释性能的研究[J].中国畜牧兽医,2010,37(11):230-234.
[10] 刘亚.硅胶表面替米考星分子印迹聚合物的制备及性能研究[D].北京:北京化工大学,2006.
[11] 杨黎燕,余丽丽,牛秀明.替米考星交联淀粉载药微球的制备研究[J].应用化工,2012,41(2):217-220.
[12] 李艳平,申宇,唐洪波.交联淀粉微球的制备及表征[J].粮油加工,2015(1):44-46,50.
[13] 苑玉凤.多指标正交试验分析[J].湖北汽车工业学院学报,2005,19(4):53-56.
[2] 郭腾,吴连勇,张家祥.兽用抗菌新药替米考星研究进展[J].中国兽药杂志,2002,36(7):38-39,43.
[3] MAIN B W,MEANS J R,RINKEMA L E,et al.Cardiovascular effects of the macrolide antibiotic tilmicosin,administered alone and in combination with propranolol or dobutamine,in conscious unrestrained dogs[J].Journal of veterinary pharmacology & therapeutics,1996,19(3):225-232.
[4] 远立国,鲍杰,李成明,等.替米考星肺靶向微球的研制[J].中国兽医科学,2008,38(12):1093-1097.
[5] 方亮.药剂学[M].北京:人民卫生出版社,2016:319.
[6] 徐军,陈子扬,单鹏,等.明胶微球的制备[J].中国生物制品学杂志,2012,25(2):230-232.
[7] DA FONSECA C O,LANDEIRO J A,CLARK S S,et al.Recent advances in the molecular genetics of malignant gliomas disclose targets for antitumor agent perillyl alcohol[J].Surgical neurology,2005,65(S1):52-58.
[8] PERESWETOFF-MORATH L.Microspheres as nasal drug delivery systems[J].Advanced drug delivery reviews,1998,29(1):185-194.
[9] 李仲谨,杨威,刘艳,等.替米考星淀粉微球的制备及缓释性能的研究[J].中国畜牧兽医,2010,37(11):230-234.
[10] 刘亚.硅胶表面替米考星分子印迹聚合物的制备及性能研究[D].北京:北京化工大学,2006.
[11] 杨黎燕,余丽丽,牛秀明.替米考星交联淀粉载药微球的制备研究[J].应用化工,2012,41(2):217-220.
[12] 李艳平,申宇,唐洪波.交联淀粉微球的制备及表征[J].粮油加工,2015(1):44-46,50.
[13] 苑玉凤.多指标正交试验分析[J].湖北汽车工业学院学报,2005,19(4):53-56.