Acta Phys. -Chim. Sin. ›› 2011, Vol. 27 ›› Issue (03): 547-552.doi: 10.3866/PKU.WHXB20110330


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;
  • 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).


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