Journal article
Characterization of a Multistage Continuous MSMPR Crystallization Process assisted by Image Analysis of Elongated Crystals
CHEC Research Centre, Department of Chemical and Biochemical Engineering, Technical University of Denmark1
Department of Chemical and Biochemical Engineering, Technical University of Denmark2
Technical University of Denmark3
The Hempel Foundation Coatings Science and Technology Centre (CoaST), Department of Chemical and Biochemical Engineering, Technical University of Denmark4
H. Lundbeck A/S5
This work demonstrates how quantitative image analysis can assist in the characterization of continuous crystallization processes and in the proper selection of mathematical models for the early assessment of crystal quality. An active pharmaceutical ingredient presenting an elongated crystal habit has been crystallized using two stirred tank crystallizers in series.
Using image analysis of the crystallization magma, the sources of crystal breakage in the crystallization cascade have been identified and the impact on crystal habit has been evaluated quantitatively. As it is expected for particles presenting high aspect ratios, crystal breakage preferentially occurs in the smallest plane, perpendicular to the largest dimension.
This phenomenon is hardly avoidable in downstream production, but it can be accounted with a design approach based on the real crystal dimensions. The kinetic rate equations for nucleation and crystal growth have been determined based on crystal width, from which a model for the accurate prediction of this dimension has been applied.
The predicted crystal size distribution is consistent through a moderate degree of crystal breakage during downstream processing.
Language: | English |
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Publisher: | American Chemical Society |
Year: | 2018 |
Pages: | 6455-6469 |
ISSN: | 15287505 and 15287483 |
Types: | Journal article |
DOI: | 10.1021/acs.cgd.8b00446 |
ORCIDs: | 0000-0002-4056-3823 , Dam-Johansen, Kim and Kiil, Søren |