Issue 9, 2019

Multidimensional dynamic experiments for data-rich process development of reactions in flow

Abstract

Continuous flow processing continues to garner interest in the pharmaceutical industry for the production of small-molecule drug substances given the advantages associated with improved mass and heat transfer, more facile scale-up, and smaller process footprints. However, to date, in-depth understanding and development of reactions can be hindered by limited availability of key raw materials and short timelines during the early stages of drug development. In this work, we present the benefits of nonlinear 2-dimensional dynamic experiments for characterization of flow reaction design spaces in a resource-sparing manner, expanding on recent reports around the use of transient flow experiments for reaction characterization. Experimental reaction data for a Knoevenagel condensation reaction are collected from a system operated at either steady state or under dynamic conditions varying one or two reaction parameters simultaneously in a linear or nonlinear pattern. These experimental data are used to generate a mathematical model describing the reaction across the design space tested. It was observed that a single nonlinear 2-dimensional dynamic experiment sufficiently spans conditions in the design space enabling the development of a robust model, which can drastically improve process knowledge and risk mitigation for early- or late-stage process development of pharmaceutical drug substances.

Graphical abstract: Multidimensional dynamic experiments for data-rich process development of reactions in flow

Supplementary files

Article information

Article type
Paper
Submitted
21 2月 2019
Accepted
24 4月 2019
First published
14 5月 2019

React. Chem. Eng., 2019,4, 1637-1645

Multidimensional dynamic experiments for data-rich process development of reactions in flow

B. M. Wyvratt, J. P. McMullen and S. T. Grosser, React. Chem. Eng., 2019, 4, 1637 DOI: 10.1039/C9RE00078J

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