替米考星肠道定位制剂的制备、体外释放度考察及表征鉴定  

Preparation,in vitro Release,and Phase Identification of an Enteric-located Formulation of Tilmicosin

作　　者：刘栩沂 陈芷欣 王鸿鑫 叶钰莹 韩梓杰 张楠 张德显 邓桦 杨鸿 LIU Xuyi;CHEN Zhixin;WANG Hongxin;YE Yuying;HAN Zijie;ZHANG Nan;ZHANG Dexian;DENG Hua;YANG Hong(College of Life Science and Engineering,Foshan University,Foshan 528231,China)

机构地区：[1]佛山科学技术学院生命科学与工程学院,佛山528231

出　　处：《中国畜牧兽医》2024年第5期2132-2142,共11页China Animal Husbandry & Veterinary Medicine

基　　金：广东省高校科技服务重点领域专项(2021ZDZX4015)。

摘　　要：【目的】采用固体分散体技术制备替米考星肠溶制剂,提高替米考星在酸中的稳定性,使其在小肠定位释放,提高替米考星的溶解速率和生物利用度,为该药的新剂型开发和临床应用提供理论参考。【方法】采用丙烯酸树脂Eudragit L100和聚乙烯吡咯烷酮(PVP)组成二元载体,采用共沉淀法制备肠道pH触发定位释放型制剂。以体外累积溶解度为评价指标,采用正交试验研究最佳制备条件,并选择X-射线衍射法、傅里叶变换红外光谱法和扫描电镜法鉴定物相。【结果】最佳的替米考星固体分散体肠溶制剂制备工艺是联合载体Eudragit L100∶PVP=10∶1、药载比为1∶2,搅拌时间为2 h,固化时间为12 h,该制剂在酸性介质中2 h溶出量<10%,在pH 6.8的缓冲溶液中2 min内溶出度为75.02%,10 min时完全溶解,大大提高了替米考星的溶解速度。X-射线衍射分析显示,固体分散体在17°和23°衍射强度高于替米考星原料药;傅里叶变换红外光谱显示,替米考星固体分散体在1593和1457 cm-1尖锐吸收峰消失;扫描电镜图中可看出替米考星均匀地分散在载体中,表明替米考星固体分散体的形成。【结论】本研究选用联合载体成功制备替米考星固体分散体肠溶制剂,其在酸中稳定,在pH 6.8缓冲液中有较好的溶出度。【Objective】The experiment was aimed to prepare enteric formulations of temicoxacin using solid dispersion technology,improve its stability in acid,enable its targeted release in small intestine,improve its dissolution rate and bioavailability,and provide theoretical references for the development and clinical application of new dosage forms of the drug.【Method】Acrylic resin Eudragit L100 and polyvinylpyrrolidone(PVP)were used to form a binary carrier,and the intestinal pH-triggered localized release formulation was prepared by the co-precipitation method.With in vitro cumulative solubility as the evaluation index,the optimal preparation conditions were screened by orthogonal test,and X-ray diffraction,Fourier infrared spectroscopy and scanning electron microscopy were used for the identification of the physical phase.【Result】The optimal preparation process of tilmicosin solid dispersion enteric formulation was Eudragit L100∶PVP=10∶1,drug-carrying ratio of 1∶2,stirring time of 2 h,curing time of 12 h.The dissolution of this formulation was<10%in an acidic environment for 2 h,and the degree of solubility reached 75.02%in buffer solution at pH 6.8 for 2 min,and it was completely dissolved in 10 min,which significantly improved the dissolution rate of tilmicosin.The dissolution rate of tilmicosin was significantly improved.X-ray diffraction result showed that the diffraction intensity of the solid dispersion at 17°and 23°was higher than that of tilmicosin API.Fourier infrared spectroscopy result showed that the sharp absorption peaks of solid dispersion of tilmicosin at 1593 and 1457 cm-1 were disappeared.Scanning electron microscopy diagrams showed that tilmicosin had been uniformly dispersed in the carrier,the solid dispersion of tilmicosin was formed.【Conclusion】Tilmicosin solid dispersion enteric formulation was prepared successfully by choosing the combined carrier,which was stable in acid and dissolved in pH 6.8 buffer with a good dissolution degree.

关 键 词：替米考星 肠道定位制剂 固体分散体 溶出度 表征鉴定 

分 类 号：S859.53[农业科学—临床兽医学]