Solubility determination, computational modeling, Hansen solubility parameters and apparent thermodynamic analysis of brigatinib in (ethanol + water) mixtures

The solubility and various thermodynamic parameters of an antitumor drug brigatinib (BRN) in various ethanol (EtOH) + water (H2O) mixtures were determined in this study. The mole fraction solubility (xe) of BRN in various (EtOH + H2O) mixtures including pure EtOH and pure H2O was obtained at T = 298.2-323.2 K and p = 0.1 MPa by adopting a saturation shake flask method. Hansen solubility parameters (HSPs) of BRN, pure EtOH, pure H2O and (EtOH + H2O) mixtures free of BRN were also computed. The xe values of BRN were correlated using Van't Hoff, Apelblat, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-Van't Hoff models with mean errors of <2.0%. The maximum and minimum xe value of BRN was obtained in pure EtOH (1.43 × 10-2 at T = 323.2 K) and pure H2O (3.08 × 10-6 at T = 298.2 K), respectively. The HSP of BRN was also found more closed with that of pure EtOH. The xe value of BRN was obtained as increasing significantly with the rise in temperature and increase in EtOH mass fraction in all (EtOH + H2O) mixtures including pure EtOH and pure H2O. The data of apparent thermodynamic analysis showed an endothermic and entropy-driven dissolution of BRN in all (EtOH + H2O) mixtures including pure EtOH and pure H2O.