(328a) Multidimensional Dynamic Experiments in Flow As a Kinetic Platform for Data Rich Experimentation in Pharmaceutical Process Development

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. A need exists for the development of scalable reaction platforms enabling extensive reaction characterization in a data-rich manner using minimal material and time. Transient reaction experiments provide a viable process development intensification option to fill this gap. One common misconception of flow chemistry is that steady-state needs to be achieved in order to extract meaningful information. Recent studies have utilized dynamic conditions to rapidly obtain reaction profiling data for the generation of kinetic models [1,2,3,4]. In this presentation, we will discuss the development and application of an automated continuous flow reactor operated transiently for both process optimization and kinetic investigations in support of drug substance development.

[1] Mozharov, S.; Nordon, A.; Littlejohn, D.; Wiles, C.; Watts, P.; Dallin, P.; Girkin, J.M. J. Am. Chem. Soc. 2011, 133, 3601-3608.

[2] Hone, C.A.; Holmes, N.; Akien, G.R.; Bourne, R.A.; Muller, F.L. React. Chem. Eng. 2017, 2, 103-108.

[3] Moore, J.S.; Jensen, K.F. Angew. Chem., Int. Ed. 2014, 53, 470-473

[4] Aroh, K.C.; Jensen, K.F. React. Chem. Eng. 2018, 3, 94-101.