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• Study the solubility of macitentan (form I) in three mixed solvents; • The solubility data were correlated by some thermodynamic models; • Statistical analysis of calculation results; • Some thermodynamic properties of dissolution process were evaluated. Due to macitentan (form I) is hydrophobic and has poor solubility, in this work, the solubility of macitentan in (methanol + ethyl acetate), (ethanol + ethyl acetate) and (isopropanol + ethyl acetate) was studied and correlated. In three mixed solvents, the solubility increased with the increase of temperature. In pure solvents, the largest mole solubility data was in ethyl acetate (1.223 × 10−2 at 313.15 K), followed by methanol (6.02 × 10−4 at 313.15 K), ethanol (4.58 × 10−4 at 313.15 K) and isopropanol (2.46 × 10−4 at 313.15 K). The solubility increased monotonically with the increase of ethyl acetate mass fraction at all studied temperatures. In mixtures of (ethyl acetate + methanol), the values varied from 6.02 × 10−4 to 1.223 × 10−2 at 313.15 K, an increase of 20.32 folds, meanwhile, 26.70 folds for mixtures of (ethanol + ethyl acetate) and 49.72 folds for mixtures of (isopropanol + ethyl acetate). The values of relative average deviations (RAD) in three systems with Jouyban-Acree model are 6.20%, 5.95% and 4.95%, respectively. For CNIBS/R-K model, the data is less than 5.0% at the temperature range from 273.15 K to 293.15 K only in mixture of (ethyl acetate + methanol). However, the data of Residual Sum of Squares (RSS) for Jouyban-Acree model and CNIBS/R-K model are 5.72 and 2.26, respectively. According to the result of analysis, the CNIBS/R-K model could provide a suitable prediction in three mixed solvents. In the following, the analysis of apparent thermodynamic properties for the dissolution processes indicate the dissolution process is not only endothermic but also entropy-driving. [ABSTRACT FROM AUTHOR]

• The solubility of doxofylline in pure and binary solvents. • The solubility data were correlated by some thermodynamic models. • The effect of solvent properties on the solubility was analysed. • Some thermodynamic properties of dissolution process were evaluated. Crystallization and purification is an important step in drug preparation. In this work, the solubility of doxofylline in some pure and mixed solvents at T = 273.15–313.15 K was experimentally determined under 101.2 kPa. Infrared spectroscopy (IR) was used to evaluate the crystal form of doxofylline, and no solvates or new form formation were observed during the whole experiment. In pure solvent, the solubility data increased with the increasing temperature. At 313.15 K, the solubility maximum value (mole fraction) was obtained in ethyl acetate (3.8552 × 10−2), followed by acetonitrile (2.8699 × 10−2), ethanol (1.7179 × 10−2), methanol (0.7069 × 10−2), iso propanol (0.4928 × 10−2) and n-propanol (0.1533 × 10−2), and similar trend was obtained at each temperature studied. In mixture of (isopropanol + ethyl acetate), the solubility increased monotonically with the increasing mass fraction of ethyl acetate at each temperature studied. The Apelblat equation and λh equation were applied to correlate the solubility data in selected pure solvents. All relative average deviation (RAD) values in the modified Apelblat equation are less than those in λh equation. Therefore, modified Apelblat is more suitable for correlating the solubility profile in selected pure solvents. In addition, Jouyban-Acree model was used to evaluate the results in mixed solvents, and the RAD value is 5.48%. During the dissolution process, the apparent dissolution standard enthalpy (Δ H sol o), apparent molar standard Gibbs energy (Δ G sol o) and apparent dissolution standard enthalpy (Δ S sol o) were calculated. The values of Δ H sol o and Δ S sol o are all positive in this experiment, which indicates the dissolution process is not only endothermic but also entropy-driving. Moreover, the contribution of dissolution enthalpy, (% ξ H) is greater than entropy (% ξ TS ) to the change of dissolution Gibbs energy in the dissolution process. [ABSTRACT FROM AUTHOR]