Study of Baclofen Solubility in Supercritical CO2 with and without Cosolvents: Experimental Analysis, Thermodynamic Evaluation, and Machine Learning Methods

This study investigates the solubility of Baclofen in supercritical CO2, which is essential for developing an efficient drug delivery system using supercritical processes. Solubility measurements were carried out in supercritical CO2, both with and without the presence of various cosolvents (ethanol and dimethyl sulfoxide (DMSO)), across a temperature range of 308-338 K and a pressure range of 12-30 MPa. Baclofen exhibited solubility ranging from 1.62 x 10-5 to 2.30 x 10-5 mole fractions in pure supercritical CO2. In the presence of cosolvents, the solubility increased from 5.76 x 10-5 to 12.79 x 10-5 mole fractions with ethanol and from 3.50 x 10-5 to 7.02 x 10-5 mole fractions with DMSO. Indeed, the addition of ethanol and DMSO cosolvents increased the solubility of Baclofen by approximately 3.55-5.56 times and 2.15-3.05 times, respectively. Several density-based empirical models and thermodynamic models (Soave-Redlich-Kwong (SRK) and Peng-Robinson (PR) equations of state) were used to correlate the solubility data. Jafari Nejad's model for the supercritical CO2-Baclofen system and Jouyban's model for supercritical CO2-ethanol/DMSO-Baclofen systems displayed higher consistency. Also, the PR model showed better accuracy in correlating Baclofen solubility in pure supercritical CO2, while SRK outperformed in supercritical CO2-ethanol/DMSO cosolvents. Moreover, machine learning exhibited exceptional accuracy, with over 99% of the predictions closely matching the experimental data, emphasizing its outstanding performance.