Getting it Right in Flow

Did you know that here at AM Technology we have fully equipped chemistry and process laboratories to assist with converting processes from batch to flow? Mike Kenny sat down with our principal chemist Martin Monedero and chemical engineer Andrew Karras to gain an insight into the approach that they take when given batch chemical process data from a client.

Mike: What's the first thing that you look for when you have a batch process in front of you that will be transferred over to a continuous process in a Coflore system?

Andrew: To start off with, I am always most interested in finding out the reaction time and whether or not the reaction is heat-transfer limited. You will often see exothermic reactions such as nitrations have steps that take several hours in batch because reagents have to be added dropwise in order to control the heat evolution. As our Coflore systems have a vastly increased heat transfer coefficient, we are able to avoid the need to have to add reagents through dropwise addition, meaning that we can substantially shorten the reaction time. This can have a significant impact on the reaction throughput and it is not uncommon to see reaction that take several hours in batch being done in flow with a ~10-minute residence time.

Render of a Coflore ACR Flow Reactor
The Coflore ACR Flow Reactor

Mike: What sort of scale do you typically carry out the testing on?

Martin: To begin with, we tend to carry out small-scale testing in a vial or round-bottomed flask to familiarise ourselves with the chemistry. As you can imagine, we have a varied client base and so the chemistry can vary quite drastically from project to project! Our go-to flow system for 95% of feasibility trials is the Coflore ACR as it is perfectly sized to allow us to screen a lot of parameters such as reaction temperature, residence time and pressure whilst using minimal material. Once we have screened these initial parameters we then have a pretty good idea as to which direction should be taken to push the reaction efficiency.

Martin and Sofia working in the flow chemistry lab at AM Technology
Martin and Sofia busy working in the lab!

Mike: Does the peripheral equipment largely stay the same for each study?

Andrew: There is so much variation when it comes to peripheral kit for flow reactors in general. Using unsuitable peripheral kit can have a very detrimental impact on the process, particularly if the reaction involves slurries. Fortunately, the team at AMT have decades of experience in this department and we can often draw upon a host of previous case studies and internal testing to guide our choice of kit for each client study. This does tend to mean that each set-up has key differences from the previous one, to cater to the specific process being investigated. We generally like to start with as simple a set-up as possible and then build from there - a peristaltic pump for example is actually an extremely versatile pump and excellent for handling slurries with a simple set-up. As part of our initial work for slurry applications we perform tests on material handling such as determining settling times and bulk densities to allow us to estimate what the minimum fluid velocity has to be to prevent solids from settling out in the lines before they reach the Coflore kit in question. Once the slurry is in the ACR / ATR / RTR then the mechanical agitation takes care of the rest!

Mike: Sounds complicated! How does all this information get translated over to the client?

Martin: Part of our feasibility testing is to make it as easy as possible for our clients to operate their processes in flow and so for each study we prepare a detailed report that outlines exactly how we set up the system in-house (including all peripheral kit!) and what we would recommend. Our engineers are also always on hand and happy to chat to clients to help them get set up and running!

Mike: That sounds great! So how can people get in touch?

Martin: If they send an email over to then we can arrange a call to chat through what they want to achieve. It doesn't have to be an existing process, we can also work at the R&D scale to help you develop a novel process that might benefit from running continuously. We take IP very seriously and are always happy to sign an NDA in advance of any specific chemistry details being shared!

“One of today's most important tools for modernizing the pharmaceutical industry is a process known as continuous manufacturing”