Continuous spherical crystallization of escitalopram oxalate without additives
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Author (Corporation)
Publication date
22.01.2024
Type of student thesis
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Type
01A - Journal article
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Parent work
Organic Process Research & Development
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Volume
28
Issue / Number
2
Pages / Duration
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Publisher / Publishing institution
American Chemical Society
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Abstract
In pharmaceutical manufacturing, needle- or plate-like crystals, fines, and broad crystal size distributions (CSDs) are highly undesired critical quality attributes hampering downstream processes like filtration, drying, milling, and tableting. When such attributes cannot be avoided, manufacturers rely on additional unit operations such as granulation to enlarge and homogenize the product’s CSD. Spherical crystallization can achieve the same results directly during crystallization by inducing a controlled agglomeration with the addition of a bridging liquid. However, this comes at the price of increased process design complexity (i.e., selection of bridging liquid and compatibility with solvents). Also, excessive agglomeration exacerbates the risk of impurity incorporations (i.e., bridging liquid and preexisting impurities). In this work, we investigate the feasibility of manufacturing spherical agglomerates of escitalopram-oxalate via cooling crystallization in a lab-scale mixed-suspension, mixed-product-removal crystallizer, notably without employing additives. We identify key operating parameters that allow tuning the agglomerates’ degree of sphericity and mechanical strength and allow increasing the homogeneity of the CSD. The method, when viable, can be easily implemented for the process intensification of purified pharmaceuticals with a simple polymorphic landscape.
Keywords
Crystallization, Crystals, Ethanol, Solvents, Supersaturation
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ISBN
ISSN
1083-6160
1520-586X
1520-586X
Language
English
Created during FHNW affiliation
No
Strategic action fields FHNW
Publication status
Published
Review
peer-reviewed
Open access category
Closed
License
Citation
Aprile, G., Szakter, K., Byrholtz Andersen, M., Wu, H., Sin, G., Skovby, T., Dam-Johansen, K., & Vetter, T. (2024). Continuous spherical crystallization of escitalopram oxalate without additives. Organic Process Research & Development, 28(2). https://doi.org/10.1021/acs.oprd.3c00345