Solubility of ibrutinib in supercritical carbon dioxide (Sc-CO2): Data correlation and thermodynamic analysis

[Display omitted] •Ibrutinib drug solubility in Sc-CO2 was determined for the first time.•Experiments were carried out at different temperatures (308–338 K) and pressures (120–270 bar).•Semi-empirical and EoS models were tested for correlating and modeling the solubility of the drug.•Self-consistency of the data was established by the Mendez-Santiago-Teja model.•Ibrutinib drug enthalpies were estimated for the first tome. Ibrutinib (PCI-32765), marketed under the trade name IMBRUVICA, is a first-in-class irreversible inhibitor drug of Bruton tyrosine kinase (BTK). In the current research, its solubility was measured at operational conditions 120–270 bar and 308–338 K, for the first time. The drug solubility has been reported between 3.90×10-6 to 1.30×10-5 based on mole fraction. Analysis of the curves confirms strong dependency of ibrutinib solubility to operational conditions due to their direct effect on solvating power of solvent. Also, pressure effect was more pronounced at the higher temperatures and the cross-over point was located around 170 bar. Besides, theoretical investigation and computational approach were carried out to correlate and extrapolate the experimental solubility of this medicine using thermodynamic models based on different approaches; semi-empirical models, activity coefficient (modified model of Margules), fugacity coefficient (mPR and mRK cEoSs) and dilute solution theory by the model of Wang-Tavlarides. Best correlation results were obtained by the modified model of Margules (AARD = 6.68%) and the empirical model of Jouybanet al., (9.62%). Additionally, different enthalpies of ibrutinib-Sc-CO2 system were estimated.