Determination of solubilities in water and 1-octanol of nitrogen- bridgehead heterocyclic compounds

Miklós Józan, K. Takács-Novák

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The solubilities in water and 1-octanol of 22 nitrogen-bridgehead quinazolone derivatives were investigated. The data were determined with a conventional method, with the typical confidence intervals at 95% probability level about ±5% and the precision good enough to evaluate the influence of structural modifications and to compare data with the lipophilicity of molecules. Solubilities in water spanned five orders of magnitude depending on the substituents attached to the ring-system. The solubility in octanol was generally somewhat higher and the range was only three magnitudes. Aqueous solubilities were more sensitive to structural changes than those in octanol. Solubility ratios were computed and fitted to the predictive relationship with two independent variables proposed by Yalkowsky. The equation with solubility ratios gave better results than the one calculated with experimental log P (partition coefficient) values. That corresponds to the known difference of solubility ratios (log SR) and log P values, caused mainly by the mutual solubility of two phases in log P measurements. The solubility ratio and the partition coefficient have the same trend but the values differ significantly. Thus the partition coefficient and the solubility ratio are not recommended for estimation of aqueous solubility (log S(w)) data of these compounds.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume159
Issue number2
DOIs
Publication statusPublished - Dec 15 1997

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1-Octanol
Heterocyclic Compounds
Solubility
Nitrogen
Water
Octanols

Keywords

  • Aqueous solubility
  • Estimation of aqueous solubility
  • Estimation of lipophilicity through solubility data
  • Estimation of log P
  • Nitrogen-bridgehead compounds
  • Solubility in octanol
  • Solubility ratio

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Determination of solubilities in water and 1-octanol of nitrogen- bridgehead heterocyclic compounds. / Józan, Miklós; Takács-Novák, K.

In: International Journal of Pharmaceutics, Vol. 159, No. 2, 15.12.1997, p. 233-242.

Research output: Contribution to journalArticle

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