Solution thermodynamics of sulfadiazine in some ethanol + water mixtures

The solubility of sulfadiazine (SD) in several cosolvent mixtures was measured at temperatures from 293.15 to 313.15 K in all the polarity range provided by aqueous mixtures conformed by ethanol and water. The solubility was maximal in the mixture 0.80 in mass fraction of ethanol (δ = 30.0 MPa1/2) and minimum in pure water (δ = 47.8 MPa1/2) at all the temperatures. 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 calorimetric values related to a drug fusion process reported in the literature. A nonlinear enthalpy-entropy relationship was observed in a plot of enthalpy vs. Gibbs energy of mixing. The plot of ΔmixH° vs. ΔmixG° shows two different trends according to the slope obtained; that is, i) one with a negative slope from pure water up to 0.20 in mass fraction of ethanol and another one from the mixture 0.80 in mass fraction of ethanol up to pure ethanol; and ii) one with a positive slope from the mixture 0.20 in mass fraction of ethanol up to the mixture 0.80 in mass fraction of ethanol. Accordingly, the driving mechanism for SD solubility in water-rich and ethanol-rich mixtures is the entropy, whereas, between 0.20 and 0.80 mass fraction of ethanol the driving mechanism is the enthalpy. This behavior is similar to the one exhibited by the similar drug sulfapyridine.