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The equilibrium solubilities of sulfanilamide, SULFAMETHIZOLE (cas 144-82-1) and sulfapyridine in methanol + water mixtures at 298.15 K were determined and the preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals. In all cases the drug solubility was the lowest in neat water and highest in neat methanol. The preferential solvation parameters for methanol (δx1,3) are negative in water-rich mixtures but positive in compositions from 0.32 in mole fraction of methanol to pure methanol. Based on these results it is conjecturable that in the former case hydrophobic hydration around the aromatic rings plays the main role in the drug’s solvation. The higher solvation by methanol in mixtures of similar cosolvent compositions and in methanol-rich mixtures can be explained in terms of the higher basic behavior of this co-solvent interacting with the Lewis acidic groups of the drugs. Besides, the drugs’ solubilities were mathematically represented by using the Jouyban–Acree model obtaining average percentage deviations lower than 2.6 % for correlative studies.
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