Coupling of the population balance equation into a two-phase model for the simulation of combined cooling and antisolvent crystallization using OpenFOAM

• Published in: Computers & chemical engineering 2019-04, Vol.123, p.246-256
• Main Authors: Farias, Lauren F.I., de Souza, Jeferson A., Braatz, Richard D., da Rosa, Cezar A.
• Format: Article
• Language: English
• Subjects: Computational fluid dynamics; Pharmaceutical crystallization; Pharmaceutical manufacturing; Population balance models; Two-phase model
• ISSN: 0098-1354; 1873-4375
• DOI: 10.1016/j.compchemeng.2019.01.009

•Proposes a two-phase model for combined cooling and antisolvent continuous-flow crystallization.•Incorporates full crystal size distribution and crystals settling effect.•Demonstrates that spatial fields for the antisolvent mass fraction and crystal nucleation and growth rates can be highly asymmetric for small continuous-flow crystallizers.•Shows that continuous-flow crystallizers of small dimension can generate bimodal crystal size distributions. This article proposes a two-phase Eulerian-Eulerian model coupled with granular kinetic theory, semi-discrete population balance equations, energy balance, and scalar transport equations for the simulation of the full crystal size distribution and the effects of particle settling in continuous-flow crystallizers. The model capabilities are demonstrated by application of an OpenFOAM® implementation to the combined cooling/antisolvent crystallization of Lovastatin in a coaxial mixer. The simulations show that (1) the spatial fields for the antisolvent mass fraction and crystal nucleation and growth rates can be highly asymmetric for small continuous-flow crystallizers, (2) continuous-flow crystallizers of small dimension can generate bimodal crystal size distributions, and (3) a relatively small change in the inlet feed velocity can change the crystal size distribution from being unimodal to bimodal. These results demonstrate the potential of the proposed model for gaining insights into continuous-flow crystallization that can be useful for the design of equipment or operations.