[en] A compact, fully integrated, and automated system is developed for end-to-end production, purification, and formulation of the active pharmaceutical ingredient (API) lidocaine hydrochloride, a widely used local anesthetic. The purification strategy includes appropriate combination of extraction, reactive crystallization, and antisolvent cooling crystallization that enables the production of lidocaine hydrochloride formulated solution, for topical application meeting US Pharmacopeia (USP) standards. Based on the optimal yield observed in each step, the system sustains a daily production of 810 doses (dosage strength = 20 mg mL-1 i.e. 2% formulation in commercial denomination).
Disciplines :
Chemistry
Author, co-author :
Monbaliu, Jean-Christophe ; Université de Liège > Département de chimie (sciences) > Center for Integrated Technology and Organic Synthesis - CiTOS
Stelzer, Torsten; University of Puerto Rico Medical Sciences Campus > Department of Pharmaceutical Sciences
Revalor, Eve; University of Melbourne > Department of Chemical and Biomolecular Engineering
Weeranoppanant, Nopphon; Massachusetts Institute of Technology - MIT > Department of Chemical Engineering
Jensen, Klavs; Massachusetts Institute of Technology - MIT > Department of Chemical Engineering
Myerson, Allan; Massachusetts Institute of Technology - MIT > Department of Chemical Engineering
Language :
English
Title :
Compact and Integrated Approach for Advanced End-to-end Production, Purification, and Aqueous Formulation of Lidocaine Hydrochloride
Publication date :
2016
Journal title :
Organic Process Research and Development
ISSN :
1083-6160
eISSN :
1520-586X
Publisher :
American Chemical Society, Washington, DC, United States
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Defense Advanced Research Project Agency (DARPA) and Space and Naval Warfare Systems Center Pacific (SSC Pacific) under Contract No. N66001-11-C-4147.
Poechlauer, P.; Manley, J.; Broxterman, R.; Gregertsen, B.; Ridemark, M. Org. Process Res. Dev. 2012, 16, 1586-1590 10.1021/op300159y
Adamo, A.; Beingessner, R. L.; Behnam, M.; Chen, J.; Jamison, T. F.; Jensen, K. F.; Monbaliu, J.-C. M.; Myerson, A. S.; Revalor, E. M.; Snead, D. R.; Stelzer, T.; Weeranoppanant, N.; Wong, S. Y.; Zhang, P. Science 2016, 352, 61-67 10.1126/science.aaf1337
ACS. Sustainable U.S. Manufacturing in the Chemical and Allied Industries https://www.acs.org/content/dam/acsorg/sustainability/acsandsustainability/sustainablemanufacturing/roadmaps/smrt-summary-sustainable-us-manufacturing-in-the-chemical-and-allied-industries-pdf.pdf (accessed April 20, 2016).
Jensen, V.; Rappaport, B. A. N. Engl. J. Med. 2010, 363, 806-807 10.1056/NEJMp1005849
Gray, A.; Manasse, H. R. Bull. World Health Organ. 2012, 90, 158-158A 10.2471/BLT.11.101303
Dolgin, E. Nat. Med. 2011, 17, 522 10.1038/nm0511-522b
http://www.fda.gov/drugs/drugsafety/drugshortages/default.htm (accessed April 20, 2016).
Plumb, K. Chem. Eng. Res. Des. 2005, 83, 730-738 10.1205/cherd.04359
Ingham, R. J.; Battilocchio, C.; Fitzpatrick, D. E.; Sliwinski, E.; Hawkins, J. M.; Ley, S. V. Angew. Chem., Int. Ed. 2015, 54, 144-148 10.1002/anie.201409356
Mascia, S.; Heider, P. L.; Zhang, H.; Lakerveld, R.; Benyahia, B.; Barton, P. I.; Braatz, R. D.; Cooney, C. L.; Evans, J. M. B.; Jamison, T. F.; Jensen, K. F.; Myerson, A. S.; Trout, B. L. Angew. Chem., Int. Ed. 2013, 52, 12359-12363 10.1002/anie.201305429
Stelzer, T.; Wong, S. Y.; Chen, J.; Myerson, A. S. In ISIC 2014 19th International Symposium of Industrial Crystallization; Biscans, B., Ed.; Toulouse, France, 2014; pp 10-13.
Myerson, A. S.; Krumme, M.; Nasr, M.; Thomas, H.; Braatz, R. D. J. Pharm. Sci. 2015, 104, 832-839 10.1002/jps.24311
FDA. Lidocaine Hydrochloride (Xylocaine) Injection. FDA Drug Shortages. http://www.accessdata.fda.gov/scripts/drugshortages/default.cfm (accessed April 20, 2016).
Minogue, S. C.; Ralph, J.; Lampa, M. J. Anesth. Analg. 2004, 99, 1253-1257 10.1213/01.ANE.0000132779.27085.52
Taddio, A.; Nulman, I.; Goldbach, M.; Ipp, M.; Koren, G. J. Pediatr. 1994, 124, 643-648 10.1016/S0022-3476(05)83150-6
DailyMed. LIDOCAINE HYDROCHLORIDE AND EPINEPHRINE-lidocaine hydrochloride and epinephrine bitartrate injection, solution; http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c70e173-5af8-4d10-7b92-d6076a6ba821 (accessed April 20, 2016).
Glazer, S.; Portenoy, R. K. J. Pain Symptom Manage. 1991, 6, 30-39 10.1016/0885-3924(91)90069-G
Williams, D. R.; Stark, R. J. Cephalalgia 2003, 23, 963-971 10.1046/j.1468-2982.2003.00623.x
Frieden, J. Am. Heart J. 1965, 70, 713-715 10.1016/0002-8703(65)90399-6
FDA. 0.4% and 0.8% LIDOCAINE HYDROCHLORIDE and 5% DEXTROSE INJECTION, USP-AQUEOUS SOLUTIONS FOR ACUTE MANAGEMENT OF CARDIAC ARRHYTHMIAS; http://www.accessdata.fda.gov/drugsatfda-docs/label/2014/018388s084lbl.pdf (accessed April 20, 2016).
Elder, D.; Facchine, K. L.; Levy, J. N.; Parsons, R.; Ridge, D.; Semo, L.; Teasdale, A. Org. Process Res. Dev. 2012, 16, 1707-1710 10.1021/op300216x