Abstract
This study presents a model to predict the solubility of a nonpolar drug DA in the presence of other nonpolar drugs D1…Dn in a complexing ligand L system such as hydroxypropyl‐β‐cyclodextrin (HPβCD). Using an equilibrium approach, the model describes the molecular interactions among these drug species and the ligand. The model indicates that the solubility of DA invariably decreases as a result of the presence of D1…Dn. Furthermore, the decrease in DA 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, 17α‐hydroxyprogesterone, and progesterone) were used as model compounds in HPβCD solutions. The experimental data showed that the solubility of any particular drug decreased in the presence of other drugs. At all tested HPβCD 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. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2301–2306, 2002
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