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

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Drug manufacturing in a fridge-sized box

Commodity chemicals tend to be manufactured in a continuous fashion. However, the preparation of pharmaceuticals still proceeds batch by batch, partly on account of the complexity of their molecular structures. Adamo et al. now present an apparatus roughly the size of a household refrigerator that can synthesize and purify pharmaceuticals under continuous-flow conditions (see the Perspective by Martin). The integrated set of modules can produce hundreds to thousands of accumulated doses in a day, delivered in aqueous solution.

Science, this issue p. 61; see also p. 44

Abstract

Pharmaceutical manufacturing typically uses batch processing at multiple locations. Disadvantages of this approach include long production times and the potential for supply chain disruptions. As a preliminary demonstration of an alternative approach, we report here the continuous-flow synthesis and formulation of active pharmaceutical ingredients in a compact, reconfigurable manufacturing platform. Continuous end-to-end synthesis in the refrigerator-sized [1.0 meter (width) × 0.7 meter (length) × 1.8 meter (height)] system produces sufficient quantities per day to supply hundreds to thousands of oral or topical liquid doses of diphenhydramine hydrochloride, lidocaine hydrochloride, diazepam, and fluoxetine hydrochloride that meet U.S. Pharmacopeia standards. Underlying this flexible plug-and-play approach are substantial enabling advances in continuous-flow synthesis, complex multistep sequence telescoping, reaction engineering equipment, and real-time formulation.

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