Solubility of sulfamethizole in some propylene glycol + water mixtures at several temperatures

The solubility of sulfamethizole (SMZ) in propylene glycol + water cosolvent mixtures was determined at temperatures from 293.15 to 313.15 K. The solubility was maximal in pure propylene glycol and very low in pure water at all the temperatures. The thermodynamic functions: Gibbs energy, enthalpy, and entropy of solution and of mixing 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 drug fusion process. A nonlinear enthalpy–entropy relationship was observed from a plot of enthalpy vs. Gibbs energy of solution. The plot of ΔsolnH° vs. ΔsolnG° shows two different trends, one with negative slope from pure water up to 0.20 mass fraction of propylene glycol and the other one positive beyond this composition up to pure propylene glycol. Accordingly, the driving mechanism for SMZ solubility in water-rich mixtures is the entropy, probably due to water-structure loss around the drug non-polar moieties by effect of propylene glycol, whereas, above 0.20 mass fraction of propylene glycol the driving mechanism is the enthalpy, probably due to SMZ solvation increase by the co-solvent molecules. This behavior is similar to the one exhibited by sulfanilamide and other drugs in the same co-solvent mixtures.

► The sulfamethizole solubility was maximal in pure propylene glycol and minimal in pure water.
► Thermodynamic quantities of solution and mixing were obtained for sulfamethizole.
► A non-linear plot of ΔsolnH° vs. ΔsolnG° compensation is found for sulfamethizole at 303.0 K.