FLOW CHEMISTRY
avoid unwanted side reactions, which is often difficult in largescale batch operations
• Hazardous materials: Handling and storing dangerous raw materials like intermediates mixed with nitric and sulfuric acids increases operational complexities and cost
• Environmental Concerns: Waste by-products from this process must be managed carefully to help prevent pollution, adding further challenges to the process
As shown in Table 1, Corning’ s AFR continuous flow process technology outperformed traditional batch processes with 6,000 tonnes / year of R-NO 3 across fixed investment, footprint, personnel requirements and operational costs.
Additional benefits include modular design, compact size, system automation, efficient heat and mixing capabilities, as well as enhanced production safety, economic efficiency and production effectiveness. Compared to a G4, the latest G5 model’ s offer additional 5 % cost and 20 % capex reductions.
R-NO 3 continuous manufacturing powered by AFR technology has been operating for nearly seven years. Its end-to-end continuous flow design uses smaller reaction volumes together with continuous downstream separation and purification, reducing the risks associated with exothermic or hazardous reactions and separations compared to batch processes.
Case study: AFR in APIs & KSMs
APIs and KSMs are additional areas where AFR technology has been increasingly utilised in the last decade. In 2023, Corning established its Advanced-Flow Pharmaceutical Technologies( AFPT) business to help bridge the gap between flow process development and the industrial realisation of continuous flow manufacturing for
G5 reactors at Zheijang Weihua New Material site
the pharmaceutical industry by expediting the transition to flow.
One end-to-end API production demonstration line built in Suzhou, China in 2023( pictured) has a threestep ibuprofen synthesis reaction unit, phase separation unit, and a solid formation unit( crystallisation, filtration, drying, etc.) with PATs of infrared sensors and ultraperformance liquid chromatography at a flow throughput of 10 kg / hour. From left to right is the three-step reaction unit followed by separation / purification and solid formation unit at 10 kg / hour flow rate.
This demonstration line was able to complete the three-step reaction, separation and purification in 40 minutes( ten of reactions and 30 of separation steps). A traditional batch process manufacturing would take 18 days to complete, with three days for the reactions and 15 days for the separation steps.
Another example of an industrial installation utilising AFR technology producing APIs is India’ s Laurus Labs, who installed a G4 unit at its Visakhapatnam facility in 2023( pictured). Laurus’ s CDMO business has used it in a multi-purpose continuous flow plant suitable for producing various pharmaceuticalrelated chemicals for global clients.
Agro case studies
In a different field, a large-scale application installation at Zhejiang
Weihua New Material in China( pictured) showcases the continuous manufacturing of agrochemical intermediates using G5 reactors together with a continuous downstream separation and purification processing.
They reduced the overall system footprint by 90 % within the facility compared to previous batch processes, which occupied six 3,000L reactors for diazotisation and three 6,000L reactors for hydrolysis steps. Table 2 shows their performance compared to batch processes in terms of yield improvements, reduced solid waste generation and fewer production staff.
Likewise, Corning has worked with BASF to scale up one synthesis step towards a future agrochemical product from laboratory to pilot scale in just few weeks utilising AFPT. The joint team effectively delivered an optimised process, leveraging Corning’ s G1 production system, in four weeks, produced 300 kg of new chemical compound for evaluation with a yield and purity improvement compared to batch production. ●
Dr Yi Jiang
DIVISION VICE PRESIDENT
CORNING, INC. k + 1 607-442-2680 J reactors @ corning. com j www. corning. com / reactors
42 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981