KEY POINTSNippon Soda, Active Pharma and the University of Tokyo develop a continuous-flow process for iguratimodPolystyrene-supported NHC catalyst enables stable long-duration operation and simpler post-reaction processingResearch stems from a 2023 alliance on continuous-flow manufacturing for pharmaceuticals and agrochemicals
The process uses a polystyrene-supported NHC catalyst and delivered a 75% total yield in research tied to a 2023 pharma-agrochemical alliance. Photo by Crystal Kwok on Unsplash
Crystal Kwok
Nippon Soda Co. and Active Pharma Co., a unit of Mitani Sangyo Co., have developed a manufacturing process for the anti-rheumatic drug iguratimod using continuous-flow synthesis in collaboration with researchers at the University of Tokyo, the companies said on Aug. 7.
The process uses an NHC organic catalyst immobilized on polystyrene resin to create a more efficient and sustainable synthesis route for iguratimod, a drug used to treat rheumatoid arthritis. The research was published in ACS Sustainable Chemistry & Engineering, a journal of the American Chemical Society.
The work was carried out under a 2023 technology alliance between Nippon Soda and the Mitani Sangyo group aimed at the practical application and commercialization of continuous-flow methods for pharmaceutical and agrochemical production, according to the release. The project combined Nippon Soda’s chemical process technology, Active Pharma’s active pharmaceutical ingredient manufacturing capabilities and the University of Tokyo’s research expertise.
The companies said they succeeded in synthesizing iguratimod with the continuous-flow process using the immobilized catalyst, which promotes reactions without metals. They also demonstrated long-duration continuous operation with a proprietary catalyst while maintaining stable reactivity, and recovered iguratimod through relatively simple post-reaction treatment and recrystallization.
Total yield from the starting materials reached 75%. Under optimized conditions, the process stably produced about 1.8 grams of an iguratimod precursor over 24 hours of continuous operation. The researchers also introduced real-time analysis using inline NMR to precisely control feed rate, temperature and other reaction conditions during extended runs.
The companies said conventional iguratimod production involves multiple steps and relatively large volumes of organic solvents, creating challenges for environmental impact and manufacturing efficiency. Continuous-flow production is being studied in the pharmaceutical industry as a way to improve process control, safety and waste reduction, particularly for active pharmaceutical ingredients.
Iguratimod is widely used as a rheumatoid arthritis treatment in Japan. The release said its medical importance has increased in recent years, citing reported applications in suppressing severe COVID-19 progression.
Active Pharma, established in 2009, develops, manufactures and sells active pharmaceutical ingredients and operates a production site in Yatsuo, Toyama Prefecture. Mitani Sangyo posted consolidated revenue of 117.53 billion yen for the fiscal year ended March 2026 and had 3,569 employees. Nippon Soda, founded in 1920, manufactures products including agrochemicals, pharmaceuticals and specialty chemicals.
AloJapan.com