Predicting solubility in multiple nonpolar drugs-cyclodextrin system
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Updated: Sep 28, 2026

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
Luwei Zhao1, Edward Orton, N Murti Vemuri
1Global Pharmaceutical Development, Aventis Pharmaceuticals, Bridgewater, New Jersey 08807, USA. luwei.zhao@aventis.com
Abstract:
This study presents a model to predict the solubility of a nonpolar drug D(A) in the presence of other nonpolar drugs D(1) em leader D(n) in a complexing ligand L system such as hydroxypropyl-beta-cyclodextrin (HPbetaCD). Using an equilibrium approach, the model describes the molecular interactions among these drug species and the ligand. The model indicates that the solubility of D(A) invariably decreases as a result of the presence of D(1) em leader D(n). Furthermore, the decrease in D(A) solubility is related to the sum of the products of the intrinsic solubilities of the other drugs and drug-ligand complexation constants. To test the model, three steroids (prednisolone, 17alpha-hydroxyprogesterone, and progesterone) were used as model compounds in HPbetaCD solutions. The experimental data showed that the solubility of any particular drug decreased in the presence of other drugs. At all tested HPbetaCD concentrations, these experimental solubility data were in good agreement with the predicted solubility data. This result lends strong support to the reliability and effectiveness of the proposed model.
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