Thermodynamic properties of flufenamic and niflumic acids--specific and non-specific interactions in solution and in crystal lattices, mechanism of solvation, partitioning and distribution

J Pharm Biomed Anal. 2007 Nov 30;45(4):679-87. doi: 10.1016/j.jpba.2007.01.039. Epub 2007 Feb 1.

Abstract

Temperature dependency of saturated vapour pressure and the thermochemical characteristics of the fusion process were measured for flufenamic acid and niflumic acid, and thermodynamic functions of sublimation, fusion and evaporation calculated. An approach to split specific and non-specific energetic terms in crystal lattices is developed. The melting points of the considered molecules correlate with the ratio between specific and non-specific interactions in crystal lattices. Temperature dependencies of the solubility in buffers with pH 2.0 and 7.4, in n-octanol and in n-hexane were measured. The thermodynamic functions of solubility, solvation and transfer processes were deduced. Specific and non-specific solvation terms were distinguished by the transfer from "inert"n-hexane to the other solvents. Comparison of the ratio between specific and non-specific interactions in solid state and in the solutions was carried out. A diagram to analyse energetic terms of partitioning and distribution processes is introduced.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Calorimetry, Differential Scanning
  • Crystallization
  • Drug Design*
  • Drug Interactions
  • Energy Transfer
  • Flufenamic Acid / chemistry*
  • Molecular Structure
  • Niflumic Acid / chemistry*
  • Solubility
  • Solutions
  • Solvents / chemistry
  • Thermodynamics*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Solutions
  • Solvents
  • Niflumic Acid
  • Flufenamic Acid