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  • Title: Excess free energy approach to the estimation of solubility in mixed solvent systems I: Theory.
    Author: Williams NA, Amidon GL.
    Journal: J Pharm Sci; 1984 Jan; 73(1):9-13. PubMed ID: 6694092.
    Abstract:
    An approach is developed by which the solubility of an organic compound in mixed solvents may be estimated. In this approach, an expression for the excess Gibbs free energy of mixing for multicomponent solvent systems was used to obtain parameters characteristic of the interaction between the solvents. A fairly simple equation which predicts the solubility of a solute in a binary solvent system over the entire solvent composition range was then derived. The equation may be partitioned into terms that contain (a) pure solvent solubilities, (b) solvent-solvent interaction contributions, and (c) contributions from the solute-mixed solvent interactions. The required data are the molar volume of the solute, the pure solvent solubilities, and, theoretically, one experimentally determined solubility in a solvent mixture. The equation can be easily extended for systems with three or more solvents.
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