响应面法优化沙拉沙星/β-环糊精包合物制备工艺与稳定性评价  

Optimization of preparation technology and stability evaluation of sarafloxacin/β-cyclodextrin inclusion complex by response surface method

作　　者：姜兴粲 李冰 杨敏[1,2,3] 张继瑜 JIANG Xingcan;LI Bing;YANG Min;ZHANG Jiyu(Key Laboratory of Veterinary Pharmaceutical Development,Ministry of Agriculture and Rural Affairs,Lanzhou 730050,China;Key Laboratory of New Animal Drug Project of Gansu Province,Lanzhou 730050,China;Lanzhou Institute of Husbandry and Pharmaceutical Sciences,Chinese Academy of Agricultural Sciences,Lanzhou 730050,China)

机构地区：[1]农业农村部兽用药物创制重点实验室,甘肃兰州730050 [2]甘肃省新兽药工程重点实验室,甘肃兰州730050 [3]中国农业科学院兰州畜牧与兽药研究所,甘肃兰州730050

出　　处：《浙江农业学报》2021年第3期404-412,共9页Acta Agriculturae Zhejiangensis

基　　金：“十二五”国家科技支撑计划(2015BAD1101);国家现代农业产业技术体系专项(CAR-37)。

摘　　要：为制备沙拉沙星/β-环糊精包合物微囊,解决沙拉沙星原药溶解度低,理化性质不稳定的问题。通过响应面法优化沙拉沙星/β-环糊精包合物的制备工艺,采用液相色谱法对沙拉沙星/β-环糊精包合物进行载药量及溶解度测定,以干燥失重试验和影响因素试验对沙拉沙星/β-环糊精包合物的含水量与稳定性进行评价。结果显示,优化后的包合工艺参数为沙拉沙星与β-环糊精摩尔比1∶2,搅拌温度50℃,搅拌时间4 h,喷雾干燥工艺为温度160℃,泵速6.3 r·min^(-1)。液相色谱方法学结果表明:沙拉沙星在质量浓度9.94~99.40μg·mL^(-1)范围内,线性关系优良,回归方程为Y=34.66X-15.867,相关系数为0.9999。影响因素试验与干燥失重试验表明,制备的沙拉沙星/β-环糊精包合物物理化学性质稳定,包合物含水量小于2%,流动性良好。结果表明,沙拉沙星/β-环糊精包合物的成功制备明显改善了药物的理化性质,对沙拉沙星的应用与推广具有积极作用。To prepare sarafloxacin/β-cyclodextrin inclusion complex microcapsules,and to solve the problems of low solubility and unstable physicochemical properties of sarafloxacin,the preparation process of sarafloxacin/β-cyclodextrin inclusion complex was optimized by response surface method,and the drug loading and solubility of sarafloxacin/β-cyclodextrin inclusion complex were determined by high performance liquid chromatography(HPLC).The water content and stability of sarafloxacin/β-cyclodextrin inclusion complex were evaluated by drying weight loss test and influencing factors experiment.The results showed that the optimized inclusion process parameters were as follows:molar ratio of sarafloxacin toβ-cyclodextrin 1∶2,stirring temperature 50℃,stirring time 4 h,spray drying temperature 160℃,pump speed 6.3 r·min-1.The results of the liquid chromatographic methodology verified showed that the linear relationship of sarafloxacin was good in the range of 9.94~99.40μg·mL-1.The regression equation was Y=34.66X-15.867,and the correlation coefficient was 0.9999.The experiments of influencing factors and drying weight loss showed that the physical and chemical properties of the prepared sarafloxacin/β-cyclodextrin inclusion complex were stable,the water content of the inclusion complex was less than 2%,and the fluidity was good.The results showed that the successful preparation of sarafloxacin/β-cyclodextrin inclusion complex significantly improved the physical and chemical properties of the drug and played a positive role in the application and popularization of sarafloxacin.

关 键 词：沙拉沙星 Β-环糊精 包合物 制备工艺 响应面法 

分 类 号：S859.5[农业科学—临床兽医学]