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Scaling Batch Processes

How to Develop Flow Processes

| Author / Editor: Charlotte Wiles, Michael Seipel / Doris Popp

View of the complete KiloFlow system — a flow platform which contains glass meso-scale flow reactors enabling the user to perform synthetically demanding, and often forbidden, transformations at scale in a rapid and flexible manner. On the right: Integral XT 150 thermostat used to regulate the KiloFlow meso reactor temperature (Pictures:Lauda/Chemtrix)
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View of the complete KiloFlow system — a flow platform which contains glass meso-scale flow reactors enabling the user to perform synthetically demanding, and often forbidden, transformations at scale in a rapid and flexible manner. On the right: Integral XT 150 thermostat used to regulate the KiloFlow meso reactor temperature (Pictures:Lauda/Chemtrix)

The pharmaceutical industry in particular is still dominated by flexible batch processes and segmented unit operations. Using a unique scalable flow platform, the researcher can now rapidly evaluate and optimise synthetic processes on mg quantities of material and subsequently scale the process, in order to attain the target production volumes.

It has long been discussed that micro reactors can be used for reaction screening, where low reactor volumes enable large quantities of data to be gathered rapidly using only milligrams of reagents. Once suitable reaction conditions are identified, the target volumes required for production can then, in principle, be attained using a combination of continuous operation and/or numbering-up [1].

Looking at this from a commercial stand-point however, it becomes clear that it is not economically feasible as to produce chemicals on a tonnes per annum scale would require hundreds to thousands of low volume micro channel reactors; therefore at a certain point, an increase in reactor volume is required. With the efficient thermal and mass transfer of micro reactors being key to their success, it is imperative when increasing reactor volume that the efficiency of these two processes is retained.

If this is not the case, re-optimisation is required in order to successfully translate a process from the laboratory to production and prevent the familiar ‘failure to scale’ observed for batch technology; in poorly designed systems this can be costly, both in terms of reagent consumption and time.

Batch Reactors: The ‘Scale-up’ Challenge

With these factors in mind, Chemtrix have developed a series of flow reactor platforms aimed at addressing the ‘scale-up’ challenge and affording researchers the rapid reaction screening that is needed in early process development using Labtrix (micro reactors) and the larger volume production using KiloFlow (meso reactors). Labtrix is a laboratory scale system designed for the evaluation of synthetic processes within micro reactors. Due to the small reactor volumes employed (1 to 20 µl), rapid and detailed process information can be generated using typically mg quantities of substrates, giving increased process insight into chemical transformations.

New Ways Possible with Recent Reactoor Designs

In addition, the large surface to volume ratio obtained within such reactors affords a safe processing environment for the study of previously forbidden chemistries. With an operating range of -15 to 195 ºC, maintained using a Peltier device, at a constant backpressure of 20 bar, the system enables researchers to access reaction conditions that would not be conventionally explored due to the need for specialised high temperature and pressure equipment.

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