The solubility of sulfapyridine (SP) in propylene glycol + water mixtures was determined at temperatures from 293.15 K to 313.15 K. The solubility was maximal in pure propylene glycol and minimum in pure water 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 drug fusion process. A nonlinear enthalpy-entropy relationship was observed from a plot of enthalpy vs. Gibbs energy of solution. The plot of Delta H-soln degrees vs. Delta(soln)G degrees shows two different trends, one with negative slope from pure water up to 0.30 mass fraction of propylene glycol and the other one positive beyond this composition up to pure propylene glycol. Accordingly, the driving mechanism for SP 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 0.30 mass fraction of propylene glycol the driving mechanism is the enthalpy, probably due to SP solvation increase by the co-solvent molecules. This behavior is similar to the one exhibited by sulfanilamide, sulfamethizole and other drugs in the same co-solvent mixtures. The Generated solubility data were calculated (correlated and/or predicted) with the Jouyban-Acree model in which the mean percentage deviation (MPD) of the correlated and predicted data were 9.3 +/- 8.6%, and 12.1 +/- 9.9%, respectively. The corresponding MPDs for the correlated and predicted solubilities using the log-linear model were 25.1 +/- 19.8%, and 55.1 +/- 32.4%. The density of saturated solutions was predicted using a previously trained model. The Delta H-soln degrees and Delta(soln)G degrees values were also correlated using a proposed model. (C) 2012 Elsevier B.V. All rights reserved.