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

被引:707
作者
Adamo, Andrea [1 ]
Beingessner, Rachel L. [2 ]
Behnam, Mohsen [1 ]
Chen, Jie [1 ]
Jamison, Timothy F. [2 ]
Jensen, Klavs F. [1 ]
Monbaliu, Jean-Christophe M. [1 ,3 ]
Myerson, Allan S. [1 ]
Revalor, Eve M. [1 ,4 ]
Snead, David R. [2 ,5 ]
Stelzer, Torsten [1 ,6 ]
Weeranoppanant, Nopphon [1 ]
Wong, Shin Yee [1 ,7 ]
Zhang, Ping [2 ,8 ]
机构
[1] MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[2] MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[3] Univ Liege, Dept Chem, Allee Six Aout 13, B-4000 Liege, Sart Tilman, Belgium
[4] Univ Melbourne, Dept Chem & Biomol Engn, Fac Med Dent & Hlth Sci, Melbourne, Vic 3010, Australia
[5] Georgia Pacific Chem, 2883 Miller Rd, Decatur, GA 30312 USA
[6] Univ Puerto Rico, Dept Pharmaceut Sci, Med Sci Campus, San Juan, PR 00936 USA
[7] Singapore Inst Technol, Chem Engn & Food Technol Cluster, 10 Dover Dr, Singapore 138683, Singapore
[8] Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA
关键词
CONTINUOUS MANUFACTURING SYMPOSIUM; FINAL DOSAGE FORMATION; WORK-UP; INGREDIENTS; CHEMISTRY; BATCH; TOOL;
D O I
10.1126/science.aaf1337
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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) x 0.7 meter (length) x 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.
引用
收藏
页码:61 / 67
页数:7
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