Mathematical Modeling of Layer Crystallization on a Cold Column with Recirculation

Abstract

Falling film crystallization is a novel technique used to overcome the challenges of solid and slurry handling used for continuous manufacturing in the pharmaceutical industry. The process and its performance were demonstrated recently. In this study, a dynamic model of falling film crystallization with a recirculation loop was developed in the form of coupled partial differential equations describing the effects of mass transfer, heat transfer, impurity inclusion, and crystallization kinetics. The model described the variation of processing parameters, such as the flow rate and cooling temperature, for three different crystallization solution systems (16 cases). The experimental results confirm the predictions of the model, which will provide further insights into processes in which experimental values do not exist or are difficult to obtain, such as the axial temperature profile of the falling liquid film or the overall purity of the deposited crystal layer at different time intervals.

The Dependence of Effective Distribution Coefficient on Growth Rate and Mass Transfer Coefficient for P-Xylene in Solid-Layer Melt Crystallization

“…Figure 6 shows that G increases with increasing ∆T for both mixtures. All the data in Figure 6 fitted to Equation ( 2) lead to G = 3.59 × 10 −7 ∆T 1.1 (14) where the line represents the fitted correlation with the correlation coefficient R 2 = 0.887. Figures 7 and 8 show the experimental results of k eff versus G for each C mt,im from the PX/OX and PX/EB mixtures, respectively, based on the measured data of C cry,im using Equation (9).…”

“…Traditionally, two modes, including the static melt crystallization and falling film melt crystallization, have been widely applied in industries. A number of studies have been published to model the crystal layer growth and impurity distribution processes for various types of solid-layer melt crystallization [6][7][8][9][10][11][12][13][14][15][16]. Basically, in these models, the fundamental energy balance and mass balance equations at the moving crystal layer surface are developed to determine the increase of the solid layer thickness and impurity distribution along the time with sufficient thermal property data.…”

Design of a Combined Modular and 3D-Printed Falling Film Solution Layer Crystallizer for Intermediate Purification in Continuous Production of Pharmaceuticals

“…Despite significant development in the field of continuous crystallization for pharmaceutical applications over the past decade it remains a relatively challenging operation to design and operate for the purpose of intermediate purification. Intermediated purification via continuous crystallization has the requirement to handle supersaturated streams with long residence times, 33 transfer slurries, filter, 34 in some cases convey wet filter cake, wash, and dissolve for further processing. As such, conventional continuous crystallizers cannot easily fulfill the workhorse role for intermediate purification and solvent swapping as batch crystallization in pharmaceutical synthesis.…”

Porosity Distribution Simulation and Impure Inclusion Analysis of Porous Crystal Layer Formed via Polythermal Process

“…Layer crystallization is known to be the effective and important separation technique in water treatment, chemical engineering, food industry, seawater desalination and other fields [1][2][3][4][5][6][7][8][9]. Crystal layers of a multiple geometrical nature were obtained as hyperpure or special-featured product using various supersaturated degree-generating mechanisms.…”

“…The outstanding fluid transfer property benefits the separation strategy, and the classic sweating (melting) process can be omitted due to the control of inclusion in the closed pores of the crystal layer [44]. The obtained pure crystal can then be melted or dissolved by hyperpure water to prepare a relevant hyperpure solution for various industrial uses [7,45,46].…”