Hansen, TB, Simone, E orcid.org/0000-0003-4000-2222, Nagy, Z et al. (1 more author) (2017) Process Analytical Tools to control polymorphism and particle size in batch crystallization processes. Organic Process Research & Development, 21 (6). pp. 855-865. ISSN 1083-6160
Abstract
In this work, process analytical technology (PAT) based approaches for controlling the polymorphism and crystal size of a nonsteroidal anti-inflammatory drug (piroxicam) during batch cooling crystallization has been investigated. Previously obtained results regarding the crystallization behavior of the different polymorphs of piroxicam in a small-scale (100 mL) crystallizer have been used to design and to initiate the control approach described in this paper. The results of the present work demonstrated the challenge of reproducing the crystallization process with respect to the product polymorphism at different scales. The solute concentration has been proved to be a critical parameter in determining the polymorphism of piroxicam in the small-scale crystallization experiments; however, the same operation parameters could not yield the same polymorph in the crystallization in 2 L crystallizers. Both direct nucleation control (DNC) and supersaturation control (SSC) have been proven to be effective at controlling the polymorphism of piroxicam in seeded cooling crystallization; furthermore, applying DNC also improved the particulate properties (larger crystal size).
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Process Research and Development, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.oprd.7b00087. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Crystallization, Polymorphism, Direct nucleation control (DNC), PAT, Piroxicam, Supersaturation control (SSC) |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 23 May 2017 10:59 |
Last Modified: | 17 May 2018 00:38 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/acs.oprd.7b00087 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:116763 |