Solubility of nonelectrolytes in polar solvents IV: Nonpolar drugs in mixed solvents

S. H. Yalkowsky, S. C. Valvani, G. L. Amidon

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

The molecular and group surface area approach to solubility is shown to be applicable to mixed aqueous solvent systems. An equation is derived which is consistent with the exponential increase in the aqueous solubility of nonpolar drugs that frequently accompanies the addition of a cosolvent. This equation predicts that: (a) the ability of a drug to be solubilized by a cosolvent is proportional to its hydrophobic surface area per molecule, and (b) the ability of a cosolvent to solubilize any drug is inversely proportional to its interfacial tension against a reference liquid hydrocarbon. These predictions are experimentally verified with solubility studies of several alkyl p‐aminobenzoates in propylene glycol‐water mixtures and of hexyl p‐aminobenzoate in mixtures of water with ethanol, methanol, ethylene glycol, propylene glycol, glycerin, and formamide.

Original languageEnglish (US)
Pages (from-to)1488-1494
Number of pages7
JournalJournal of pharmaceutical sciences
Volume65
Issue number10
DOIs
StatePublished - Oct 1976
Externally publishedYes

Keywords

  • Alkyl p‐aminobenzoates—solubility in propylene glycol‐water mixtures
  • Cosolvent systems, polar—solubility of nonelectrolytes, molecular and group surface area approach
  • Hexyl p‐aminobenzoate—solubility in mixed polar solvent systems
  • Nonelectrolytes—solubility in mixed aqueous solvent systems
  • Polar solvents, mixed—solubility of nonelectrolytes, molecular and group surface area approach
  • Solubility—nonelectrolytes in mixed aqueous solvent systems, molecular and group surface area approach

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Solubility of nonelectrolytes in polar solvents IV: Nonpolar drugs in mixed solvents'. Together they form a unique fingerprint.

Cite this