Combining Radial and Continuous Flow Synthesis to Optimize and Scale-up the Production of Medicines

• Mara Guidi^a,b
• Sooyeon Moon^a,b
• Lucia Anghileri^a,b
• Dario Cambié^a
• Peter H. Seeberger*^a,b
• Kerry Gilmore*^a,c

• ^aDepartment of Biomolecular Systems Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1, 14476 Potsdam (Germany)
• ^bDepartment of Chemistry and Biochemistry Freie Universität Berlin Arnimallee 22, 14195 Berlin (Germany)
• ^cUniversity of Connecticut, Storrs, CT 06269 (United States)

Current drug production in batch cannot adapt rapidly to market demands, evidenced by recent shortages in many markets globally of essential medicines. Flow chemistry is a valuable tool for on-demand production of active pharmaceutical ingredients (APIs). Here, we reveal a new concept to develop and produce APIs, where an automated synthesizer that works with discrete volumes of solutions is employed at the discovery stage to identify the optimal synthetic route and conditions before a commercially available continuous flow system is used for scale-up. This concept is illustrated by the synthesis of nifedipine and paracetamol, in short supply in Germany during the COVID-19 pandemic, and the local anesthetic lidocaine.

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