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

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9.94~99.40 μg·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0.999 9。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。

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

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 to β-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 9.94~99.40 μg?mL-1. The regression equation was Y=34.66X-15.867, and the correlation coefficient was 0.999 9. 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.