A Hybrid CFD Compartmentalization Modeling Framework for the Scaleup of Batch Cooling Crystallization Processes

Abstract

Crystallizer design is often hindered by the lack of scaleup rules, hydrodynamic information, and predictive crystallization modeling tools. A hybrid CFD compartmentalization batch cooling crystallizer model is proposed to take into account localized mixing, heat transfer, and fluid hydrodynamics, combined with key process engineering information obtained on a laboratory scale. The compartments were identified using CFD simulations based on the crystallizer geometry and operating conditions. The population, mass, concentration, and energy balance of each compartment is modeled separately as a well-mixed MSMPR unit with input and output streams. The software gPROMS (Process Systems Enterprise Limited) is a process-modeling tool that can facilitate compartmental modeling and will be used for the prediction of the crystallization behavior upon scaleup.

The Metastability and Nucleation Thresholds of Ibuprofen in Ethanol and Water-Ethanol Mixtures

“…About 70% of solid products are produced in crystal form [1,2]. The quality of the crystals, such as size and shape, and the progress of the operation are generally considered to be better when crystallization is undertaken inside the MSZ (metastable zone) below the SNT [3][4][5][6] (secondary nucleation threshold). The upper limit of the primary nucleation MSZ is the primary nucleation threshold (PNT), while that for the secondary nucleation is the SNT.…”

Comprehensive sensitivity analysis and process risk assessment of large scale pharmaceutical crystallization processes

“…This is achieved by defining the entire vessel as a network of interconnected ideally mixed subvolumes (compartmental zones), in which no or negligible gradients exist. Overall flow pattern, temperature distribution, concentration, local energy dissipation and solid distribution can be regarded as base criterion for determination of the compartments in crystallization vessels [26,27,28].…”

Scale-Up of a Semi-Batch Draft Tube Baffled Crystallizer for Hexanitrohexaazaisowurtzitane Based on Experiments and Computational Fluid Dynamics Simulation

“…8 Hybrid CFD compartment modeling with process simulation was utilized for the scale-up of batch cooling crystallization processes. 9 This study highlighted the influence of flow fields, kinetics, and crystal size distribution on the design and scale-up of MSMPR crystallizer. Bezzo et al 10 employed a multizonal approach as a multiscale strategy in bioreactor modeling with CFD to predict fluid flow and in process simulation for kinetic analysis.…”

“…The above papers have been used to scale-up or optimize crystallizers by combining crystallization experiments with CFD simulations. Different types of crystallizers were used: (1) Wei et al, 13 Zauner et al, 16 Song et al, 17 Malysiak et al, 18 and Zhu et al 5 used a draft tube crystallizer, (2) Kougoulous et al 9 used a simple crystallizer, (3) Schmidt et al 15 used a conical base reactor, (4) Oslo experiments and CFD simulations were performed on fluidized-bed crystallizers by Al-Rashed et al, 19 and (5) Bell 21 explained crystallization and scale-up criterion. Table 1 above discusses the scale-up of crystallizers using experimental outcomes and software by several authors.…”