Thermodynamics of solubility of the weak water-soluble bioactive compound isatin in various {polyethylene glycol 400 (PEG 400) + water} mixed solvent systems were studied using Van't Hoff and Krug analysis. The solubility of isatin was measured from T = (298.15 to 338.15) K at atmospheric pressure using the shake flask method. Values of the measured solubility were correlated with three semi-empirical models that included an ideal model, the modified Apelblat model and Yalkowsky model. The root mean square deviations were observed to be less than 4.00% by all three semi-empirical models. All three models showed a correlation coefficient of about 0.99. The mole fraction solubility of isatin was found to be highest in pure PEG 400 (9.85 . 10(-2) at T = 298.15 K) and lowest in pure water (5.14 . 10(-5) at T = 298.15 K) over the region studied from T = (298.15 to 338.15) K. The results of thermodynamic parameters (dissolution enthalpy, Gibbs free energy and dissolution entropy) indicated an endothermic, spontaneous and entropy driven dissolution process of isatin in all (PEG 400 + water) mixed solvent systems. (C) 2014 Elsevier Ltd. All rights reserved.