Cheaper, Faster, Smaller, Cleaner
Flow Chemistry – Prospects for Fine & Specialty Chemicals and Pharma
- Rectangular channels for optimized heat transfer in a Miprowa reactor. © Ehrfeld Mikrotechnik
- Integration of the continuously running Miprowa flow reactors into the existing building infrastructure at Shaoxing Eastlake in China. © Ehrfeld Mikrotechnik
- “Our Miprowa technology offers a time-efficient and integrated scale-up based on established equipment concepts.” Anne Kaaden, key account manager, Ehrfeld Mikrotechnik
Developed and technically proven around 1995, micro reaction technology was probably highly overestimated for the first 10 years and underestimated for the next 10 years. Meanwhile it is on its way to an established process technology, not only in research and laboratory, but also in large scale production.
In flow chemistry, a chemical reaction is run in a continuously flowing stream in contrast to batch production. The subfield of micro process engineering, that deals with the design of micro-structured reactors for chemical reactions, is also known as micro reaction technology.
The technical advantages of continuous operation in micro- and milli reactors compared to batch reactors include:
- Ultra-fast mixing
- Highly efficient heat transfer
- Short and defined residence times
- Simple process control due to low system inertia
- High operational reliability due to minimum hold-up
- Improved safety
- Short development times
Especially with respect to rapid, highly exothermic, explosive or toxic reactions, whose safety risks make batch reactor use very challenging or even impossible, the characteristics of continuous flow micro and milli reactors offer clear benefits.
The economic advantages of micro reaction technology (MRT) compared to batch technology can be described with the term ‘’process intensification’’. It may sound like catch phrases, but the ‘’cheaper, smaller, cleaner’’ and ‘’making more with less” has been proven in different applications — not only in research and laboratory, but also in large scale production. This makes MRT today more interesting than ever before, not only for economic reasons but also for sustainable development.
In terms of “time to market” — in pharmaceutical and fine chemical industries of special importance — it is noteworthy to point out that the scale up from laboratory to production can be carried out more simply compared to other established technologies. The characteristic performance features of micrometer-scale laboratory apparatus correspond widely to those of millimeter-scale equipment, and further upscaling is done with numbering up.
MRT in Research and Labs
In Brazil, the Technology Center for the Chemical and Textile Industries of the National Industrial Training Service (SENAI), located in the state of Rio de Janeiro, is an organization which focuses on education and technological innovation for process industries.
One of the main activities of this center is to offer research-applied services to innovate in processes and products for the chemical industry. SENAI Innovation Institute (ISI) for Biosynthetics (one of the center divisions) for example will have a pilot scale unit that, for some sectors of the chemical industries, like paper or petrol, can be used for investigation and design of an industrial scale unit. Other clients who aim at bigger productions are asking to estimate industrial scale costs and setting technical targets for process development. Joao Bruno Valentim from ISI Biosynthetics is convinced of a huge potential for flow chemistry in the chemical industry. Once they prove it works technically, it is a matter of matching the expectations of cost reduction and reducing the impact of scale on chemical plants projects.
At the University of Graz in Austria, Oliver Kappe is professor of chemistry and scientific director of the Center for Continuous Flow Synthesis and Processing (CC FLOW) at the Research Center Pharmaceutical Engineering (RCPE). CC FLOW as an academic lab cannot provide commercial scale manufacturing but search for novel flow chemistry routes to molecules of interest. Kappe sees a lot of interest in flow chemistry both from the academic world but also in pharma and other industries. He is convinced that, given the enhanced safety and expanded process windows, there is so much you can do in flow that you cannot do in batch. The vision obviously is not that all batch chemistry will be replaced by flow, but in future there will be many more safe, reliable, and automated flow processes available to practitioners interested in both lab and commercial scale.
In Australia, the Commonwealth Scientific and Industrial Research Organization (CSIRO), which is the national research organization, has a mandate to assist the Australian chemical industry. Using the latest in flow chemistry and process technology, CSIRO can provide manufacturing solutions to rapidly synthesize small molecules and polymeric materials. Christian Hornung of CSIRO says that many of their industrial customers plan to take their synthesis route into production using continuous processing. With the new FloWorks facility opening its doors at CSIRO Clayton early in 2019, they will continue to be a center of excellence in flow chemistry working with Australian and international chemical manufacturers. He believes the new facility will help extend their offer to improve chemical manufacturing processes for companies that have not adopted or heard of flow chemistry yet.
Milli Reactors in Production Scale
Shaoxing Eastlake High-Tech is an agrochemical producer founded in China near Shanghai in 1990, which not only serves the Chinese market, but also exports its products to more than 20 countries, including the US and EU. The company provides active ingredients to the global agrochemical market segment.
In 2016, Shaoxing Eastlake commissioned a milli reactor which was designed, manufactured and supplied by Ehrfeld Mikrotechnik in Wendelsheim, Germany. The decision for their Miprowa technology was driven by achievable product quality, significantly improved yield, safety aspects and a short return on investment, says Anne Kaaden, key account manager at Ehrfeld. The continuously operated production reactor with a capacity of up to 10,000 t/y is using millistructures on a production scale and was designed for a highly exothermic alkoxylation reaction. The reactor has a nominal width of 400 mm and a length of 7 m and contains about 150 rectangular reaction channels with exchangeable static mixers. It replaced more than 20 batch reactors while doubling the original capacity.
In November 2018, Eastlake started implementing two additional milli reactors of same size, thus tripling their production capacity at its Shaoxing site up to 30,000 t/y. These three production reactors are a visible reference for micro reaction technology in production applications.