Equilibrium versus kinetic measurements of aqueous solubility, and the ability of compounds to supersaturate in solution - A validation study

Karl J. Box, Gergely Völgyi, Edit Baka, Martin Stuart, Krisztina Takács-Novák, John E.A. Comer

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

A novel potentiometric procedure has recently been described for rapid measurement of equilibrium aqueous solubility values of organic acids, bases, and ampholytes that form supersaturated solutions. In this procedure, the equilibrium solubility is actively sought by changing the concentration of the neutral form by adding HCl or KOH titrants and monitoring the rate of change of pH due to precipitation or dissolution in a process called Chasing Equilibrium. In this article, we seek to validate the procedure against a shake-flask protocol for solubility determination. A set of 16 small organic compounds, covering a wide range of solubilities was chosen for the study. Interestingly, while 10 compounds in the study were found to chase equilibrium, the others did not. Kinetic solubility data was also collected. It was noted that kinetic solubility was consistently higher than equilibrium solubility for chasers, but correlated well with equilibrium solubility for nonchasers. The ratio of kinetic to equilibrium solubility indicated a compound's ability to form supersaturated solutions.

Original languageEnglish
Pages (from-to)1298-1307
Number of pages10
JournalJournal of pharmaceutical sciences
Volume95
Issue number6
DOIs
Publication statusPublished - Jun 2006

Keywords

  • ADME
  • Analytical chemistry
  • Biopharmaceutical classification system
  • Hydrates/solvates
  • Light-scattering
  • Physical characterization
  • Physicochemical
  • Precipitation
  • Solubility
  • Supersaturation

ASJC Scopus subject areas

  • Pharmaceutical Science

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