Thermodynamic modeling of determined the optimal condition of the gas antisolvent process with different solvent

Abstract

This study investigated the liquid-phase volume expansion to optimize the gas antisolvent (GAS) process condition. During the GAS process, particle precipitation does not take place in any operational conditions. Therefore, thermodynamic models are required to select the appropriate conditions and understand the precipitation mechanism. The Peng–Robinson equation of state with van-der-Waals (vdW2) mixing rules was used for the evaluation of the proper operational conditions at the temperature ranges of 308–338 K. The volume expansion of the system was studied at different process conditions for the binary (carbon dioxide-solvent) and ternary (carbon dioxide-solvent-rosuvastatin) systems. For this purpose, rosuvastatin (ROS) and carbon dioxides were solute and antisolvent, respectively. Dimethyl sulfoxide, ethanol, propanol, butanol, and pentanol were chosen as organic solvents. The minimum pressure for the ternary (carbon dioxide-dimethyl sulfoxide-rosuvastatin) system at 308, 318, 328, and 338 K was 7.80, 8.58, 9.79, and 11.1 MPa, respectively. The effect of solvent on volume expansion and minimum pressure was investigated. The calculated Pmin was 80, 82.4, 85.4, and 89.4 bar for ethanol, butanol propanol, and pentanol at 318 K respectively. According to modeling results, there was a direct relationship between the molecular weight of solvent with the same structure and minimum pressure.

Keywords

• Volume expansion
• Group contribution
• Rosuvastatin
• Solvent
• Precipitation