Evaluation of Solid–Liquid Equilibria for Ternary Pharmaceutical Compound + Water + Cyclodextrin or Its Derivative Systems with Wilson and Modified Chrastil Models

Abstract

The solid–liquid equilibria (SLE) of ternary mixtures of pharmaceutical compound + water + solid cosolvent cyclodextrin (CD) were calculated using the Wilson equation as the activity coefficient model, to evaluate the cosolvency of CD for poorly water-soluble pharmaceutical compounds. The pharmaceutical compounds were etodolac and famotidine. The cosolvents were CD and its derivatives, i.e., α-CD, β-CD, 2-HP-β-CD, 2-HE-β-CD, and M-β-CD. A simple group contribution method was constructed to predict the enthalpy of fusion of the CDs, which is needed to calculate the SLE of the system containing CD. The binary interaction parameters in the Wilson equation Λij were determined from solubility data for the pharmaceutical compounds and CDs in pure water and from experimental ternary data. The calculated solubilities were compared with those obtained using the modified Chrastil model. The proposed method gave almost the same calculation accuracies to the modified Chrastil model using fewer fitting parameters.

Keywords

• Pharmaceutical compounds
• Cyclodextrin
• Solid–liquid equilibria
• Wilson model
• Modified Chrastil model