Thermodynamic Modeling of the Gas-Antisolvent (GAS) Process for Precipitation of Finasteride

Abstract

Experimental study of the effect of gas antisolvent (GAS) system conditions on the particle size distribution of finasteride (FNS) requires a thermodynamic model for the volume expansion process. In this study, the phase behavior of the binary system including carbon dioxide and Dimethyl sulfoxide, and a ternary system comprising carbon dioxide, dimethyl sulfoxide, and Finasteride was studied. The Peng-Robinson equation of state was employed for the evaluation of the fluid phases and a fugacity expression to represent the solid phase. By developing an accurate predictive model, the GAS operating conditions can be optimized to produce particles with no need for a large number of experiments. First, the critical properties of the FNS were evaluated by the group contribution methods. The method of Marrero and Gani was also selected to predict the normal boiling point, critical temperature, and critical pressure. The correlation of Edmister was chosen for the prediction of the acentric factor. The lowest pressures for the ternary system at 308, 318, 328, and 338 K were 7.49, 8.13, 8.51, and 9.03 MPa, respectively. The precipitation of the dissolved finasteride happened at these operating pressures.

Keywords

• finasteride
• genetic algorithm
• group contribution
• supercritical fluid
• thermodynamic modeling