Solubility and stability of anhydrate/hydrate in solvent mixtures

Haiyan Qu*, Marjatta Louhi-Kultanen, Juha Kallas

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

60 Citations (Scopus)


In this paper, the thermodynamics of the anhydrate/dihydrate carbamazepine (CBZA/CBZH) in ethanol-water mixtures was studied by measuring the solubility of anhydrate and dihydrate carbamazepine at 0-60 °C. Both stable form solubility and metastable form solubility were measured, the latter with the assistance of Raman immersion probe. The thermodynamic properties of the anhydrate/dihydrate system, such as the relative stability, and enthalpy and entropy of dissolution, were estimated by plotting the measured solubility data according to the van't Hoff equation. The anhydrate/dihydrate carbamazepine showed an enantiotropic relationship in the studied mixtures and temperature ranges. It was shown that at a certain temperature, there was an equilibrium water activity value at which the anhydrate and dihydrate carbamazepine were in equilibrium. This equilibrium water activity value depends significantly on the temperature. The lower the temperature, the smaller is the water activity value needed to attain equilibrium between anhydrate and dihydrate. The obtained results are useful in determining crystallization parameters to achieve a desired anhydrate or hydrate phase. The approach can be applied to other anhydrate and hydrate systems.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalInternational Journal of Pharmaceutics
Issue number1-2
Publication statusPublished - 14 Sep 2006
MoE publication typeA1 Journal article-refereed


  • Carbamazepine
  • Hydrate
  • Metastable solubility
  • Phase transition
  • Solubility
  • Water activity


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