Issue 9, 2019

Definitive screening designs for multistep kinetic models in flow

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.

Graphical abstract: Definitive screening designs for multistep kinetic models in flow

Supplementary files

Article information

Article type
Communication
Submitted
03 mai 2019
Accepted
06 jun 2019
First published
06 jun 2019

React. Chem. Eng., 2019,4, 1565-1570

Definitive screening designs for multistep kinetic models in flow

C. A. Hone, A. Boyd, A. O'Kearney-McMullan, R. A. Bourne and F. L. Muller, React. Chem. Eng., 2019, 4, 1565 DOI: 10.1039/C9RE00180H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements