晶体微结构对恩格列净溶出性能的影响  

The influence of crystal microstructure on the dissolution performance of Empagliflozin

作　　者：代帅 朱建政 梁陈静 沈意周 陈正国 石玲玲 张国庆[1] DAI Shuai;ZHU Jianzheng;LIANG Chenjing;SHEN Yizhou;CHEN Zhengguo;SHI Lingling;ZHANG Guoqing(School of Materials Science&.Engineering,Zhejiang Scir Tech University,Hangzhou 310018,China;Yantai Environmental Sanitation Management Center,Yantai 264000,China)

机构地区：[1]浙江理工大学材料科学与工程学院,杭州310018 [2]烟台市环境卫生管理中心,山东烟台264000

出　　处：《浙江理工大学学报（自然科学版）》2022年第3期357-362,共6页Journal of Zhejiang Sci-Tech University(Natural Sciences)

基　　金：国家自然科学基金项目(22075252)。

摘　　要：为研究晶体微结构对恩格列净溶出性能的影响,采用蒸发溶剂的方法制备了具有不同微结构的恩格列净晶体产品,分别利用X射线粉末衍射仪(PXRD)、扫描电子显微镜(SEM)、高效液相色谱(HPLC)和紫外分光光度仪(UV)对制备的不同微结构恩格列净进行表征分析,并通过溶出试验对比晶体微结构导致的溶出性能差异。结果表明:在乙醇和乙酸乙酯中分别蒸发结晶得到了具有棒状结构和块状结构的恩格列净,从XRD衍射图谱可以观察到同样特征峰位置的峰强存在差异,说明不同溶剂析出的恩格列净晶体,其微结构差异显著;通过恩格列净亲脂性分析发现,棒状结构的恩格列净表面极性更大,更具亲水性;液相色谱结果显示棒状结构的恩格列净表观溶解度更高,为0.0344 mg/mL;溶出度测试结果显示,溶出时间180 min后,棒状结构和块状结构的恩格列净溶出度分别达到94.6%和92.0%,棒状结构显示出较高的溶出度。该研究表明不同微结构的恩格列净对该药物制剂的溶出性能有影响,因此通过调控药物微结构可提高难溶药物制剂的溶出度。In order to investigate the effect of crystal microstructure on the dissolution performance of Empagliflozin, Empagliflozin crystal products with microstructures were prepared by means of solvent evaporation. The characterization analysis was performed on Empagliflozin with different microstructures using X-ray powder diffraction(PXRD), scanning electron microscopy(SEM), high performance liquid chromatography(HPLC), and ultraviolet spectroscopy(UV), respectively. The results showed that rod-structured Empagliflozin and block-structured Empagliflozin were obtained through evaporative crystallization from ethanol and ethyl acetate, respectively. At the same time, it was observed from the XRD diffraction pattern that there existed difference in the peak intensity at the same characteristic peak position, indicating that the Empagliflozin crystals precipitated from different solvents have significantly different microstructures. The analysis of the lipophilicity of Empagliflozin showed that rod-structured Empagliflozin had better polarity and hydrophilicity than block-structured Empagliflozin. The liquid chromatogram results showed that the apparent solubility of rod-structured Empagliflozin was 0.0344 mg/mL, higher than block-structured Empagliflozin. The dissolution experiment results showed that after 180 min dissolution, the net dissolution rates of rod-structured Empagliflozin and block-structured Empagliflozin reached 94.6% and 92.0%, respectively. The rod-structured Empagliflozin exhibited a higher dissolution rate. The study has shown that Empagliflozin with different microstructures can affect the dissolution properties of the pharmaceutic preparation and the regulation of pharmaceutic microstructure can enhance the dissolution rate of some insoluble drugs.

关 键 词：恩格列净 微结构 重结晶 表观溶解度 溶出度 

分 类 号：R917[医药卫生—药物分析学]