Preferential solvation of sulfadiazine, sulfamerazine and sulfamethazine in ethanol + water solvent mixtures according to the IKBI method

The preferential solvation parameters of sulfadiazine, sulfamerazine and sulfamethazine in ethanol + water binary mixtures were derived from their thermodynamic properties by means of the inverse Kirkwood-Buff integrals (IKBI) method. From solvent effect studies, it is found that these sulfonamides are sensitive to solvation effects, so the preferential solvation parameter by ethanol δxE,S, is negative in water-rich and ethanol-rich mixtures but positive in compositions from 0.24 to 0.54-0.58 in mole fraction of ethanol according to the sulfonamide. It is conjecturable that in water-rich mixtures the hydrophobic hydration around aromatic rings and/or methyl groups plays a relevant role in the solvation. The more solvation by ethanol in mixtures of similar co-solvent compositions could be due mainly to polarity effects. Finally, the preference of these drugs for water in ethanol-rich mixtures could be explained in terms of the bigger acidic behavior of water interacting with hydrogen-acceptor groups in the sulfonamides.