Modeling of continuous slug flow cooling crystallization towards pharmaceutical applications
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Date
2023-09-04
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Abstract
The rising trend towards continuous production in the field of small-scale crystallization has generated many creative concepts for apparatuses for the production of active pharmaceutical ingredients. One of these promising apparatuses is the Slug Flow Crystallizer (SFC), which enables the adjustment of the particle size distribution and the achievement of high yields through its alternating slug flow. To realize and understand the crystallization inside the SFC, high experimental effort has been necessary until now. Therefore, a mechanistic model considering the hydrodynamics of slug flow, the energy and mass balances, and the crystallization phenomena of growth and agglomeration inside the apparatus was developed. Its purpose is to improve the understanding of the process, estimate the effects of operating parameters on target properties, and predict crystallization behavior for different substance systems with minimal experimental effort. Successful modeling was validated with experimental results for the substance system l-alanine/water. Furthermore, the robustness of the model was evaluated, and guidelines were presented, enabling the transfer of the model to new substance systems.
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Continuous crystallization, Active pharmaceutical ingredients, Mechanistic modeling, Slug flow crystallizer, High-quality products