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

Abstract

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 × 10^–5 to 2.30 × 10^–5 mole fractions in pure supercritical CO₂. In the presence of cosolvents, the solubility increased from 5.76 × 10^–5 to 12.79 × 10^–5 mole fractions with ethanol and from 3.50 × 10^–5 to 7.02 × 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.