Applications of Flow Chemistry for API Synthesis


Head of Technology & Innovation, Sterling Pharma Solutions Dudley, United Kingdom


Batch production remains the mainstay of the pharmaceutical manufacturing sector, and much has been discussed about how flow chemistry has the potential to offer economic and technological advantages, as well as safety benefits when handling volatile or hazardous materials.
There are now several examples of steps in API syntheses being carried out under continuous conditions, and this article will examine real-world cases where the technology has been implemented positively; what barriers exist to wider implementation in the industry; and how flow chemistry can be utilised as an important tool for chemical process development.

Flow chemistry as an approach and term has been used since the 1970s, but it was not until the turn of the millennium that the term became common in relation to fine chemical synthesis, as it was explored for application in the pharmaceutical industry. By comparison the Haber–Bosch process for ammonia synthesis, as well as hydroformylations as continuous flow processes are used at considerable scale, and have been for some time.


Where large-scale flow processes exist in the polymer, petrochemical and food industries, they tend to involve relatively simple transformations, and/or enact certain operations such as precipitation, separation and quenching. The technology is used as it offers greater control over the process and yields through temperature control, or higher volume throughputs.


For the pharmaceutical industry, synthetic processes typically involve more complex chemical transformations, with multiple steps and often require intermediate work-up and purification stages. Exploiting flow chemistry for this purpose is highly specialised and faces a number of challenges, including economic and regulatory considerations, as well ...