Solubility of hydrophobic compounds in water-cosolvent mixtures: Relation of solubility with water-cosolvent interactions

The solubility of organic compounds in mixtures of water and an organic cosolvent can be reasonably estimated from the solubility values in the neat solvents and the composition of the solvent mixture, by means of the log-linear solubilization model. However, deviations from the model are frequently observed in different degree. Such deviations, which tend to become more pronounced with decreasing polarity of the cosolvent, are to a good extent the result the nonideal mixing of water and cosolvent, due to the interactions between the two solvent components. We present a model that incorporates the effect of water-cosolvent interactions into the log-linear model. The effect of nonideality of mixing takes the form of a pseudoquadratic expression on the cosolvent concentration, obtainable from vapor pressure data of the solute-free water-cosolvent mixture. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:293-302, 2010