CO2 utilization for determining solubility of teriflunomide (immunomodulatory agent) in supercritical carbon dioxide: Experimental investigation and thermodynamic modeling

Precise design of processes involving the use of benign and green solvents such as supercritical carbon dioxide (SC CO2) in the pharmaceutical industries requires comprehensive knowledge on the solubilities of the drug in this solvent. Thus, the main goal of this research is to experimentally measure the solubility of a water-insoluble immunomodulatory agent, namely teriflunomide, in SC CO2. This important drug has been widely used as an inhibitor for some inflammatory, chronic diseases affecting the white and gray matter of the nervous system such as multiple sclerosis (MS). Solubility of teriflunomide was measured, for the first time, by a static method at temperatures and pressures ranges of 308-338 K and 120-270 bar. Solubilities were obtained in mole fraction at the mentioned operational conditions ranged from 8.84 x 10(-5)to5.43 x 10(-4) and revealed strong functionality to pressure and complicated functionality to the temperature which lead to a retrograde behavior, giving rise to a cross-over region at around 195 bar. Some different mathematical models were considered to describe solubility of teriflunomide. Concerning modeling by the cubic equation of states (cEoS), the lack of experimental values on sublimation pressure of the solute was a major obstacle, making its estimation essential and inevitable. For this purpose, a recent approach was adopted with a modified form of the Peng-Robinson cEoS. Additionally, solubilities were correlated with five well-known semi-empirical models. Some correlation results were used to check the internal consistency of experimental data and estimate the enthalpies of the teriflunomide-CO2 system. The lowest deviation was achieved by Sodeifian et al. model.

Automated summary

This study aims to experimentally measure the solubility of teriflunomide in supercritical carbon dioxide and describe the solubility using mathematical models. The results show that the solubility of teriflunomide is strongly dependent on pressure and has a complex relationship with temperature. The model proposed by Sodeifian et al. achieves the lowest deviation.