A machine learning approach for thermodynamic modeling of the statically measured solubility of nilotinib hydrochloride monohydrate (anti-cancer drug) in supercritical CO2

Nilotinib hydrochloride monohydrate (NHM) is an anti-cancer drug whose solubility was statically determined in supercritical carbon dioxide (SC-CO2) for the first time at various temperatures (308-338 K) and pressures (120-270 bar). The mole fraction of the drug dissolved in SC-CO2 ranged from 0.1 x 10(-5) to 0.59 x 10(-5), corresponding to the solubility range of 0.016-0.094 g/L. Four sets of models were employed to evaluate the correlation of experimental data; (1) ten empirical and semi-empirical models with three to six adjustable parameters, such as Chrastil, Bartle, Sparks, Sodeifian, Mendez-Santiago and Teja (MST), Bian, Jouyban, Garlapati-Madras, Gordillo, and Jafari-Nejad; (2) Peng-Robinson equation of state (Van der Waals mixing rule, had an AARD% of 10.73); (3) expanded liquid theory (modified Wilson model, on average, the AARD of this model was 11.28%); and (4) machine learning (ML) algorithms (random forest, decision trees, multilayer perceptron, and deep neural network with respective R-2 values of 0.9933, 0.9799, 0.9724 and 0.9701). All the models showed an acceptable agreement with the experimental data, among them, the Bian model exhibited excellent performance with an AARD% of 8.11. Finally, the vaporization (73.49 kJ/mol) and solvation (- 21.14 kJ/mol) enthalpies were also calculated for the first time.