Advanced Continuous Flow Platform for On‐Demand Pharmaceutical Manufacturing

Ping Zhang(Novartis (United States)), Nopphon Weeranoppanant(Burapha University), Dale A. Thomas(Massachusetts Institute of Technology), Kohei Tahara(Gifu Pharmaceutical University), Torsten Stelzer(University of Puerto Rico, Medical Sciences Campus), Mary Grace. Russell(Massachusetts Institute of Technology), Marcus O’Mahony(Vertex Pharmaceuticals (United States)), Allan S. Myerson(Massachusetts Institute of Technology), Hongkun Lin(Massachusetts Institute of Technology), Liam Kelly(Massachusetts Institute of Technology), Klavs F. Jensen(Massachusetts Institute of Technology), Timothy F. Jamison(Massachusetts Institute of Technology), Chunhui Dai(Massachusetts Institute of Technology), Yuqing Cui(Massachusetts Institute of Technology), N.E.B. Briggs(Massachusetts Institute of Technology), Rachel L. Beingessner(Massachusetts Institute of Technology), Andrea Adamo(Massachusetts Institute of Technology)
Chemistry - A European Journal
January 31, 2018
10.1002/chem.201706004
Cited by 108Open Access
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Abstract

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.

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