Solution Thermodynamics and Preferential Solvation of Sulfamerazine in Methanol plus Water Mixtures

The solubility of sulfamerazine (SMR) in methanol + water co-solvent mixtures was measured at five temperatures from 293.15 to 313.15 K. The mole fraction solubility of this sulfonamide was maximal in pure methanol (delta (1) = 29.6 MPa1/2) and minimal in water (delta (2) = 47.8 MPa1/2) at all the temperatures studied. The apparent thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from these solubility data by using the van't Hoff and Gibbs equations. Apparent thermodynamic quantities of mixing were also calculated by using the ideal solubilities reported in the literature. A non-linear enthalpy-entropy relationship was observed for SMR in the plot of enthalpy versus Gibbs energy of mixing. This plot shows two different trends according to the slopes obtained when the mixture's composition changes. Accordingly, the driving mechanism for the SMR solution process in water-rich mixtures is the entropy whereas it is the enthalpy in mixtures with mass fractions of methanol greater than 0.20. Additionally, the preferential solvation of this drug by the solvents was analyzed by means of the inverse Kirkwood-Buff integrals, which indicate that it is preferentially solvated by water in water-rich mixtures but preferentially solvated by methanol in methanol-rich mixtures.