Research Article

On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system

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Science  01 Apr 2016:
Vol. 352, Issue 6281, pp. 61-67
DOI: 10.1126/science.aaf1337
  • Fig. 1 Reconfigurable system for continuous production and formulation of APIs.

    (A) Labeled photograph of the stack of upstream synthesis modules. (B) Labeled photograph of the downstream purification and formulation modules. (C) Close-up examples of upstream units; PFA tube flow reactors in an aluminum shell for heating (left) and membrane surface tension–based separation units (right). (D) Images of some of the main components in the downstream unit including the (a) buffer tank, (b) precipitation tank, (c) filtration unit, (d) crystallization unit, (e) filtration unit, (f) formulation tank, (g) solution holding tank, and (h) formulated API. Details are in the supplementary text.

  • Fig. 2 Reconfigurable modules and flowcharts for API synthesis.

    (A) Diphenhydramine hydrochloride, (B) lidocaine hydrochloride, (C) diazepam, and (D) fluoxetine hydrochloride. The top row represents the different modules. Colored modules are active, gray boxes designate inactive modules. Reagent and solvent numbers refer to the compounds listed in table S2.

  • Fig. 3 Synthesis of diphenhydramine hydrochloride using the reconfigurable system.

    Flowchart detailing the upstream and downstream synthesis.

  • Fig. 4 Synthesis of APIs via two-step upstream configurations.

    (A) Lidocaine hydrochloride and (B) diazepam.

  • Fig. 5 Demonstration of a multistep API synthesis.

    Flowchart detailing the upstream and downstream synthesis of fluoxetine hydrochloride. DMSO, dimethyl sulfoxide; rt, room temperature; DIBAL, diisobutylaluminum hydride.

Supplementary Materials

  • On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system

    Andrea Adamo, Rachel L. Beingessner, Mohsen Behnam, Jie Chen, Timothy F. Jamison, Klavs F. Jensen, Jean-Christophe M. Monbaliu, Allan S. Myerson, Eve M. Revalor, David R. Snead, Torsten Stelzer, Nopphon Weeranoppanant, Shin Yee Wong, Ping Zhang

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

    Download Supplement
    • Materials and Methods
    • Figs. S1 to S25
    • Tables S1 to S3
    • References

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