posted on 2018-12-05, 00:00authored byChi-Hung Ho, Jieran Yi, Xiaonan Wang
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,
validating the economic feasibility of this process with a net present
value of $150 million over a 20 year time period. Therefore, this
present work demonstrates the feasibility, sustainability, and economic
competitiveness of the proposed process.