Hone, CA, Boyd, A, O'Kearney-McMullan, A et al. (2 more authors) (2019) Definitive screening designs for multistep kinetic models in flow. Reaction Chemistry and Engineering, 4 (9). pp. 1565-1570. ISSN 2058-9883
Abstract
Currently, rate-based understanding of organic reactions employed in the manufacture of active pharmaceutical ingredients (APIs) is often not obtained. In many cases, the generation of kinetic models is still seen as a specialised and time intensive activity, which can only be justified at certain instances in development. In this Communication, we report the application of a definitive screening design (DSD) in combination with reaction profiling for the efficient collection of kinetic data. The experimental data (10 profiles, 40 experimental data points) were collected within a short time frame (<1 week) within a continuous flow reactor. The data were fitted to a multistep kinetic model consisting of 3 fitted rate constants and 3 fitted activation energies. The approach is demonstrated on a Friedel-Crafts type reaction used in the synthesis of an important API. Our approach enables early identification of the sensitivity of product quality to parameter changes and the early use of process models to identify optimal process-equipment combinations in silico, significantly reducing development time and scale-up risks.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019, Royal Society of Chemistry. This is an author produced version of an article published in Reaction Chemistry and Engineering. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemical & Process Engineering (Leeds) |
Funding Information: | Funder Grant number EU - European Union 637232 Royal Academy of Engineering ISS1516/8/32 |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Jun 2019 15:07 |
Last Modified: | 06 Jun 2020 00:38 |
Status: | Published |
Publisher: | Royal Society of Chemistry |
Identification Number: | 10.1039/C9RE00180H |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:147076 |