LAUSR

This work proposes a comprehensive framework of biocatalytic continuous manufacturing of sitagliptin, the active pharmaceutical ingredient of the leading dipeptidyl peptidase-4 inhibitor antidiabetic drug. Continuous manufacturing has the advantages of quality consistency, reduced waste generation, and cost-effectiveness in comparison to batch processes. Furthermore, compared to traditional catalysts, biocatalysts have lighter environmental footprints. An end-to-end continuous manufacturing process is designed and the reaction kinetics of the biocatalytic reaction is determined according to the published data. Based on the steady-state model of a plug-flow microreactor, the optimal productivity is determined to be 2.6 × 10–2mol h–1 using surrogate-based optimization. In addition, an assessment of the process’ environmental impacts demonstrates its sustainability with a lower E-factor of 53 compared to 200 of traditional processes. A comprehensive techno-economic analysis has also been performed, validatin...