Journal of Molecular Liquids 411 (2024) 125765 Available online 13 August 2024 0167-7322/Published by Elsevier B.V. Comprehensive study of medications solubility in supercritical CO 2 with and without co-solvent; Laboratory, theoretical, and intelligent approaches Chou-Yi Hsu a, * , Dheyaa J. Jasim b , Pooja Bansal c, d , Nizomiddin Juraev e, f , Dmitry Olegovich Bokov g, h , Ameer H. Al-Rubaye i , Karrar Hatif Mohmmed j , Ahmed Huseen Redhee k, l, m , Abhinav Kumar n , Yasser Fakri Mustafa o a Thunderbird School of Global Management, Arizona State University Tempe Campus, Phoenix, Arizona 85004, USA b Department of Petroleum Engineering, Al-Amarah University College, Maysan, Iraq c Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka 560069, India d Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India e Faculty of Chemical Engineering, New Uzbekistan University, Tashkent, Uzbekistan f Scientific and Innovation Department, Tashkent State Pedagogical University, Tashkent, Uzbekistan g Institute of Pharmacy named after A.P. Nelyubin, Sechenov First Moscow State Medical University, 8 Trubetskaya St., bldg. 2, Moscow, 119991, Russian Federation h Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, 2/14 Ustyinsky pr., Moscow, 109240, Russian Federation i Department of Petroleum Engineering, Al-Kitab University, Altun Kupri, Iraq j Scientific Research Center, Al-Ayen University, Thi-Qar, 64001, Iraq k Medical laboratory technique college, the Islamic University, Najaf, Iraq l Medical laboratory technique college, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq m Medical laboratory technique college, the Islamic University of Babylon, Babylon, Iraq n Department of Nuclear and Renewable Energy, Ural Federal University Named after the First President of Russia Boris Yeltsin, Ekaterinburg 620002, Russia o Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq ARTICLE INFO Keywords: Solubility Empirical model Equation of state Supercritical CO 2 Machine learning ABSTRACT Determining the dissolution characteristics of medicines in supercritical CO 2 is vital for formulating innovative drug delivery systems through an efficient supercritical process. This study investigates the solubility of three poorly bioavailable drugs  Topiramate, Meclizine, and Dimenhydrinate- in supercritical CO 2 , both with and without ethanol co-solvent, over a temperature range of 308 K to 348 K and pressures from 17 MPa to 41 MPa. The solubility of these medicines in supercritical CO 2 (binary system) is notably low, ranging from 2.5 × 10 -6  4.54 × 10 -6 , 0.26 × 10 -5  2.3 × 10 -5 , and 0.20 × 10 -5  1.91 × 10 -5 in mole fraction, respectively. However, in the presence of ethanol (ternary system), their supercritical solubility significantly increases by factors of 2.75–5.84, 1.40–3.20, and 2.04–4.85, respectively. The supercritical solubility of the mentioned compounds are theoretically evaluated using several approaches, including empirical models, a machine learning methodology employing a multilayer perceptron neural network, thermodynamic models based on two cubic equations of state (Peng-Robinson (PR) and Soave–Redlich–Kwong (SRK)), and a non-cubic equation of state (perturbed chain-statistical associating fluid theory (PC-SAFT)), as well as two expanded liquid models (UNIQUAC and Wilson). The findings revealed that all the specified models demonstrate acceptable accuracy in correlating the experimental data of the specified drugs in both binary and ternary systems. Among these, the PR and SRK thermodynamic models, along with some empirical models, show the best results. Furthermore, the machine learning model exhibited outstanding accuracy in forecasting the supercritical solubility of the desired drugs, with over 99.9% alignment between their predicted and experimental data. * Corresponding author. E-mail addresses: hsuchou83@gmail.com, t545316@gmail.com (C.-Y. Hsu). Contents lists available at ScienceDirect Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq https://doi.org/10.1016/j.molliq.2024.125765 Received 9 February 2024; Received in revised form 13 August 2024; Accepted 13 August 2024