Solubility and preferential solvation of sulfadiazine in methanol + water mixtures at several temperatures

The solubility of sulfadiazine (SD) in some methanol + water cosolvent mixtures was measured at five temperatures from 293.15 to 313.15 K in all the polarity range. The mole fraction solubility of this drug was maximal in neat methanol (δ = 29.6 MPa1/2) and minimum in pure water (δ = 47.8 MPa1/2) at all the temperatures studied. The thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from these solubility data by using the van’t Hoff and Gibbs equations. Thermodynamic quantities of mixing were also calculated by using ideal solubility values reported in the literature. Non-linear enthalpy–entropy relationship was observed for SD in the plot of enthalpy vs. Gibbs energy of mixing, thus, ΔmixH° vs. ΔmixG° plot shows two different trends according to the slopes obtained when the mixtures composition changes. Accordingly, the driving mechanism for SD solution process in water-rich is the entropy; whereas, from 0.20 in mass fraction of methanol to neat methanol the process is enthalpy-driven. Additionally, the preferential solvation of this drug by the solvents was analyzed by means of the inverse Kirkwood–Buff integrals observing that it is preferentially solvated by water in water-rich mixtures but preferentially solvated by methanol in methanol-rich mixtures.