Enabling Mechanical Separation of Enantiomers through Controlled Batchwise Concomitant Crystallization: Digital Design and Experimental Validation
| Autor: | Joop H. ter Horst, Andrew S. Dunn, Botond Szilagyi, Zoltan K. Nagy |
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| Rok vydání: | 2020 |
| Předmět: |
RM
Quantitative Biology::Biomolecules Physics::Biological Physics Materials science Resolution (mass spectrometry) High Energy Physics::Lattice High Energy Physics::Phenomenology General Chemistry Experimental validation Condensed Matter Physics Quantitative Biology::Other law.invention Chemical engineering law QD General Materials Science Crystallization Enantiomer |
| Zdroj: | Crystal Growth & Design. 20:7726-7741 |
| ISSN: | 1528-7505 1528-7483 |
| DOI: | 10.1021/acs.cgd.0c00974 |
| Popis: | In the pharmaceutical industry the separation of chiral molecules is important due to the different physiochemical properties that the enantiomers of a chiral drug possess. Therefore, resolution techniques are used to separate such enantiomers from one another. In particular, preferential crystallization is a common technique used to separate conglomerate-forming compounds, due to its high selectivity. However, the efficient separation of enantiomers in a batchwise preferential crystallization process through seeding with the preferred enantiomer alone is still inefficient, since unwanted nucleation of the counter enantiomer is inevitable. Here, we demonstrate a model-based digital design for the separation of enantiomers for a conglomerate-forming compound (asparagine monohydrate), by using mechanical separation by sieving after crystallization, whereby the separation is enabled by a designed bias in the crystal size distributions of each enantiomer. This bias is created by a concomitant crystallization of both enantiomers using optimized seeding and cooling profiles obtained from a population balance model. In this way, a high level of control is achieved over a batchwise preferential crystallization process, since the crystallization of both enantiomers is controlled. We show that, through this separation method, material with impurity levels as low as 6 wt % can be obtained. To our knowledge this is the first demonstration of modeling such a process to separate enantiomers of a conglomerate-forming compound. |
| Databáze: | OpenAIRE |
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