Solubility of drugs in aqueous solutions. Part 3: multicomponent mixed solvent.

The results obtained previously by Ruckenstein and Shulgin [Int. J. Pharm. 258 (2003a) 193; Int. J. Pharm. 260 (2003b) 283] via the fluctuation theory of solutions regarding the solubility of drugs in binary aqueous mixed solvents were extended in the present paper to multicomponent aqueous solvents. The multicomponent mixed solvent was considered to behave as an ideal solution and the solubility of the drug was assumed small enough to satisfy the infinite dilution approximation. An expression derived for the activity coefficient of a solid solute in a multicomponent solvent was used to obtain an equation for the solubility of a drug in terms of its solubilities in two subsystems of the multicomponent solvent and their molar volumes. Ultimately the solubility can be expressed in terms of those in binary or even in individual solvents and their molar volumes. The method was applied to the solubility of tioconazole and 19-Nor-1alpha,25-dihydrovitamin D(2) in several ternary and in a quaternary aqueous mixed solvents. The predicted solubilities were compared with experimental data and good agreement was found.