Parametrization of PC-SAFT EoS for Solvents Reviewed for Use in Pharmaceutical Process Design: VLE, LLE, VLLE, and SLE Study
Jaber Yousefi Seyf, Mohammad Asgari
Abstract
The perturbed chain-statistical associating fluid theory equation of state (PC-SAFT EoS) is one of the state-of-the-art thermodynamic models used in the phase equilibrium calculation of associating mixtures, in particular, in the pharmaceutical industry. Accordingly, parametrization of the PC-SAFT EoS for approved solvents reviewed for use in pharmaceutical process design by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was done in the present study. First, the PeC-SAFT EoS model parameters for 41 pure solvents were regressed (of 62 solvents). The available high-quality binary vapor–liquid equilibrium (VLE) data (944 out of 1891 binary systems) and also binary liquid–liquid equilibrium (LLE) data were used to tune the interaction parameters of the PC-SAFT model between the 62 solvents. The interaction parameters of 944 binary systems from 1891 (50%) solvent–solvent systems were regressed. To best fit the PC-SAFT model to the experimental data of 254 binary systems, in addition to the interaction parameters of the dispersion contribution (kij), the temperature-dependent effective cross-association volume of the association contribution (kAiBj) was also fitted. The latter term plays a very important role in the fitting of the experimental VLE (systems that contain at least one associating component) and also LLE data (254 out of 944 binary systems). Using the obtained binary LLE parameters, the LLE phase behavior of 11 ternary LLE systems was successfully predicted by the PC-SAFT model. In addition, the heterogeneous residue curve map, azeotrope compositions, and temperatures of the water–ethanol–benzene system were successfully predicted by the PC-SAFT model. It was also shown that the performance of the PC-SAFT model was superior to those of UNIFAC, UNIFAC-LLE, UNIFAC-DMD, PSRK, VTPR, and UMR-PR models. Finally, the solubility of aripiprazole, cilostazol, imatinib, linagliptin, and naftopidil was regressed in pure solvents, and their solubility was successfully predicted in binary solvents. Hence, the PC-SAFT EoS in the current state together with the solvents confirmed by the ICH is a useful thermodynamic package to be used in the synthesis of active pharmaceutical ingredients, finished product formulations, and also purification operations.