The solubility of sulfadiazine (SD) in some 1,4-dioxane + water co-solvent mixtures was measured at five temperatures from 293.15 to 313.15 K in all the polarity range. By using the van't Hoff and Gibbs equations the thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from these data. The maximal solubility of this drug expressed in mole fraction was found in the mixture with 0.85 in mass fraction of 1,4-dioxane (w(1) = 0.85, delta(1+2) = 24.7 MPa1/2) and the minimum solubility in pure water (delta = 47.8 MPa1/2) at almost all the temperatures studied. By using the ideal solubility values reported in literature, the thermodynamic quantities of mixing were also calculated. Non-linear enthalpy-entropy relationship was observed for SD in the plot of enthalpy vs. Gibbs energy of solution with variable positive slopes in the regions with 0.00 <= w(1) <= 0.90 and 0.95 <= w(1) <= 1.00. Hence, the driving mechanism for SD solution process is the enthalpy in nearly all the compositions. In addition, the preferential salvation of this drug by both solvents was analyzed by means of the inverse Kirkwood-Buff integrals observing that it is preferentially solvated by water in water-rich and 1,4-dioxane-rich mixtures but preferentially solvated by 1,4-dioxane in those mixtures with intermediate compositions. (C) 2015 Elsevier B.V. All rights reserved.