Poorly soluble marketed drugs display solvation limited solubility

J Med Chem. 2007 Nov 15;50(23):5858-62. doi: 10.1021/jm0706416. Epub 2007 Oct 11.

Abstract

We determined the intrinsic aqueous solubility of 15 poorly soluble drugs with solubilities ranging from 2.9 nM to 1.1 microM. We then analyzed the data from a physicochemical perspective, using experimentally determined solid-state properties and easily interpretable two-dimensional molecular descriptors, to better understand the factors underlying poor solubility. The analysis shows that poorly soluble drugs that have reached the market are solubility limited by solvation rather than by their solid state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, High Pressure Liquid
  • Molecular Structure
  • Multivariate Analysis
  • Pharmaceutical Preparations / chemistry*
  • Principal Component Analysis
  • Solubility
  • Tandem Mass Spectrometry
  • Thermodynamics

Substances

  • Pharmaceutical Preparations