物理化学学报 >> 2010, Vol. 26 >> Issue (01): 1-6.doi: 10.3866/PKU.WHXB20100143

热力学、热化学和溶液化学 上一篇    下一篇

环丙沙星水合物与无水合物晶型的相互转变

李献文, 周鹤, 许艳, 胡一桥   

  1. 闽江学院化学与化学工程系, 福州 350108; 南京大学生命科学学院, 医药生物国家重点实验室, 南京 210093
  • 收稿日期:2009-09-11 修回日期:2009-11-07 发布日期:2009-12-29
  • 通讯作者: 胡一桥 E-mail:hu_yiqiao@yahoo.com.cn

Phase Conversion between Anhydrous and Hydrated Ciprofloxacin

LI Xian-Wen, ZHOU He, XU Yan, HU Yi-Qiao   

  1. Department of Chemistry and Chemical Engineering, Minjiang University, Fuzhou 350108, P. R. China; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, P. R. China
  • Received:2009-09-11 Revised:2009-11-07 Published:2009-12-29
  • Contact: HU Yi-Qiao E-mail:hu_yiqiao@yahoo.com.cn

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摘要：

化合物的水合状态有赖于结晶溶媒中水的活度(aH2O). 通过制备不同体积比水-有机溶媒的潜溶剂来控制aH2O, 用粉末X射线衍射(PXRD)、热重分析(TGA)和差示扫描热量(DSC)等方法表征在具有不同aH2O的水-甲醇中平衡一段时间后的过剩环丙沙星固体的结晶状态. 同时采用高效液相色谱测定环丙沙星水合物、无水合物以及它们的混合物在具有不同aH2O的水-甲醇混合溶液中的溶解度. 结果表明溶解度变化规律与在相应aH2O的水-甲醇中多余固体的晶型变化规律基本一致. 利用实验所得数据构建了环丙沙星无水合物/水合物相稳定性与aH2O的关系图. 将该图像与放置于室温以及一定相对湿度条件下时间长达十二周的样品的PXRD数据对比, 表明本实验所用的研究方法能够快速、精确地预测无水合物与水合物之间的相互转变过程以及水-有机溶媒的aH2O对它们的相对稳定性的影响.

关键词: 水合物, 无水合物, 水活度, 环丙沙星, 泥浆法

Abstract:

The hydration state of a compound depends on the activity of water (aH2O) in its crystallizing medium. This study utilized powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to investigate the crystalline states of ciprofloxacin precipitation. In these long equilibrated water-methanol systems, a series of water activities were obtained by adjusting the water-methanol volume ratios. We used high performance liquid chromatography (HPLC) to measure the solubility of ciprofloxacin hydrate, anhydrate, and their mixtures in these solutions with various water activities. The results showed that ciprofloxacin's solubility basicallychanged according to the crystallization state of the precipitated solid. A relationship was determined between the phase stability of the ciprofloxacin anhydrate/hydrate and the water activity of the solutions. By comparing the relationships we established above with the PXRD data of the ciprofloxacin samples that were stored for 12 weeks under constant relative humidity and room temperature, we found that the methodology employed in this experiment was able to accurately and efficiently predict the phase conversion between ciprofloxacin anhydrate and hydrate. We also demonstrated how the water activity could affect the relative stability of these crystalline solids in water-methanol solutions.

Key words: Hydrate, Anhydrate, Water activity, Ciprofloxacin, Slurry bridging