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

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

Research output: Contribution to journalArticle

89 Citations (Scopus)

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
StatePublished - 1976
Externally publishedYes

Fingerprint

para-Aminobenzoates
Solubility
Propylene Glycol
Pharmaceutical Preparations
Surface Tension
Ethylene Glycol
Water
Hydrocarbons
Glycerol
Methanol
Surface tension
Ethanol
Molecules
Liquids

ASJC Scopus subject areas

  • Molecular Medicine
  • Chemistry(all)
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Pharmacology

Cite this

Solubility of nonelectrolytes in polar solvents. IV. Nonpolar drugs in mixed solvents. / Yalkowsky, Samuel H; Valvani, S. C.; Amidon, G. L.

In: Journal of Pharmaceutical Sciences, Vol. 65, No. 10, 1976, p. 1488-1494.

Research output: Contribution to journalArticle

@article{1e331465e6404457a7d18042d5480ff9,
title = "Solubility of nonelectrolytes in polar solvents. IV. Nonpolar drugs in mixed solvents",
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.",
author = "Yalkowsky, {Samuel H} and Valvani, {S. C.} and Amidon, {G. L.}",
year = "1976",
language = "English (US)",
volume = "65",
pages = "1488--1494",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

TY - JOUR

T1 - Solubility of nonelectrolytes in polar solvents. IV. Nonpolar drugs in mixed solvents

AU - Yalkowsky, Samuel H

AU - Valvani, S. C.

AU - Amidon, G. L.

PY - 1976

Y1 - 1976

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0017170545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0017170545&partnerID=8YFLogxK

M3 - Article

VL - 65

SP - 1488

EP - 1494

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 10

ER -