物理化学学报 >> 2011, Vol. 27 >> Issue (03): 547-552.doi: 10.3866/PKU.WHXB20110330

热力学，动力学和结构化学 上一篇    下一篇

阿德福韦酯糖精共晶形成的热力学

张建军1, 祖卉1, 高缘2   

  1. 1. 中国药科大学药剂教研室, 南京 210009;
    2. 中国药科大学中药制剂教研室, 南京 210009
  • 收稿日期:2010-09-25 修回日期:2010-11-24 发布日期:2011-03-03
  • 通讯作者: 祖卉, 高缘 E-mail:highmorepharm@gmail.com;zuhuinj@gmail.com
  • 基金资助:

    国家重大新药创制科技重大专项新制剂与新释药系统技术平台项目(2009ZX09310-004, 2011ZX09201-101-02)资助

Formation Thermodynamics of Adefovir Dipivoxil-Saccharin Co-Crystals

ZHANG Jian-Jun1, ZU Hui1, GAO Yuan2   

  1. 1. Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, P. R. China;
    2. Department of Chinese Medicine Pharmaceutics, China Pharmaceutical University, Nanjing 210009, P. R. China
  • Received:2010-09-25 Revised:2010-11-24 Published:2011-03-03
  • Contact: ZU Hui, GAO Yuan E-mail:highmorepharm@gmail.com;zuhuinj@gmail.com
  • Supported by:

    The project was supported by the Technology Platform for New Formulation and New Drug Delivery System, Important National Science & Technology Specific Projects, China (2009ZX09310-004, 2011ZX09201-101-02).

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摘要：

测定不同温度下阿德福韦酯(AD)在系列浓度糖精(SAC)乙醇溶液中的溶解度及AD在恒温下系列浓度糖精水溶液中的溶解度, 研究AD-SAC共晶形成的热力学, 得到了共晶的溶度积(Ksp)、络合常数(K11)及反应自由能(ΔG0)等热力学参数, 建立了不同温度下的AD-SAC-乙醇三相图. 结果表明: 在乙醇中, 温度对Ksp和K11有极显著性影响(P<0.01), 随着温度的降低, Ksp逐渐减小, K11增大, 共晶的溶解为吸热过程, 共晶的形成为吸热的自发过程, 温度的下降有利于增加AD与SAC在乙醇中的络合效应. AD在SAC水溶液中的溶解度随SAC浓度的升高呈现三阶段特征, 先线性增长至平台区后再倒数下降.

关键词: 阿德福韦酯, 糖精, 共晶, 溶解度, 热力学

Abstract:

The solubilities of adefovir dipivoxil (AD) in saccharin (SAC) ethanolic solutions at different temperatures and in SAC aqueous solutions at constant temperature were determined to investigate the thermodynamic characteristics of AD-SAC co-crystals. The solubility products (Ksp), complexation constants (K11), and Gibbs free energy (ΔG0) were calculated. Ternary phase diagrams of the AD-SAC- ethanol systems at various temperatures were established. We demonstrate that temperature has significant influence on the Ksp and K11 in ethanolic solution. Ksp decreased and K11 increased with a decrease in temperature. Dissolution of the co-crystals in ethanol is an endothermic process. Co-crystal formation is a spontaneous and endothermic process. A decrease in temperature favors complexation between the AD and SAC in ethanol. In aqueous solutions of SAC, the solubility of AD shows a three- stage profile with a platform.

Key words: Adefovir dipivoxil, Saccharin, Cocrystal, Solubility, Thermodynamics