Continuous spherical crystallization of escitalopram oxalate without additives
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Autor:in (Körperschaft)
Publikationsdatum
22.01.2024
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Organic Process Research & Development
Themenheft
DOI der Originalpublikation
Link
Zugehörige Forschungsdaten
Reihe / Serie
Reihennummer
Jahrgang / Band
28
Ausgabe / Nummer
2
Seiten / Dauer
Patentnummer
Verlag / Herausgebende Institution
American Chemical Society
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
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.
Schlagwörter
Crystallization, Crystals, Ethanol, Solvents, Supersaturation
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1083-6160
1520-586X
1520-586X
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Nein
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Closed
Lizenz
Zitation
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