Measurement and modeling of rizatriptan in supercritical CO2 for pharmaceutical processing

This study examines the solubility of rizatriptan, a migraine medication, in supercritical carbon dioxide. The goal is to promote environmentally friendly drug manufacturing methods, such as antisolvent precipitation via supercritical fluids. Solubility levels were evaluated at temperatures ranging from 308.2 K to 338.2 K and pressures ranging from 12 to 30 MPa. These evaluations produced mole fraction values ranging from 0.24 × 10^-4 to 4.19 × 10^-4 and dissolution concentrations ranging from 0.008 g/L to 0.302 g/L. An estimated crossover pressure of approximately 15 MPa was identified, resulting from the interaction between the compound's vapor pressure and the fluid's density. Seven density-based models such as Chrastil, Bartle, Kumar-Johnston (K-J), and Mendez-Santiago-Teja (MST), Bian et al. and Sodeifian et al. (Ⅰ and Ⅱ) models were implemented. The Sodeifian et al. model (Ⅱ) demonstrated the strongest alignment (AARD = 7.78%, R² = 0.990). Key extracted thermodynamic metrics include the overall enthalpy (38.06 kJ/mol), the enthalpy associated with vaporization (50.55 kJ/mol), and the enthalpy linked to solvation (- 12.49 kJ/mol). Additionally, three thermodynamic equations Peng-Robinson, Soave-Redlich-Kwong, and regular solution were examined. The regular solution model produced the best results (AARD = 6.89%, R² = 0.991). These results provide reliable data and simulation models that can improve supercritical carbon dioxide methodologies, and advance eco-friendly drug production strategies.