A new predictive equation for the solubility of drugs based on the thermodynamics of mobile disorder.

The thermodynamics of mobile disorder rejects the static model of the quasi-lattice for liquids. Because cause of the perpetual change of neighbors, during the observation time of thermodynamics of the order of seconds, each molecule of a given kind in a solution has experienced the same environment and had at its disposal the same mobile volume. This domain is not localizable and not orientable. Each molecular group perpetually "visits" successively all parts of this domain. The highest entropy is obtained when the groups visit all the parts of the domain without preference. H-bonds are preferential contacts with given sites of the neighbors that cause deviations with respect to such "random" visiting, thereby decreasing the entropy. The quantitative development of these ideas leads to equations describing the effect of solvent-solvent, solute-solvent, and solute-solute hydrogen bonds on the chemical potential of the solute. A universal equation predicting the solubility of drugs in a given solvent is derived. The effect of H-bonds is governed not by "solubility parameters" but by stability constants from which the order of magnitude can be estimated. From the sole knowledge of the solubility of methylparaben in pentane, the method predicts correctly the order of magnitude of its solubility in 26 other solvents, including alcohols and water.