Article (Scientific journals)
Continuous flow synthesis and crystallization of modafinil: a novel approach for integrated manufacturing
Silva Brenes, Diana Vanessa; Agrawal, Shailesh; López-Mejías, Vilmalí et al.
2024In Reaction Chemistry and Engineering
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Keywords :
Advanced manufacturing; Continuous crystallization; Continuous-flow synthesis; Cooling crystallization; Flow synthesis; Holistic approach; Integrated manufacturing; Integration strategy; Modafinil; Optimisations; Catalysis; Chemistry (miscellaneous); Chemical Engineering (miscellaneous); Process Chemistry and Technology; Fluid Flow and Transfer Processes
Abstract :
[en] This study reports efforts toward the integrated advanced manufacturing of the anti-narcoleptic drug modafinil. It showcases a holistic approach from flow synthesis to purification via continuous crystallization. The integration strategy included a necessary optimization of the reported flow synthesis for modafinil, enabling prolonged operation and consistent crude quality. The reactor effluents were subsequently processed downstream for purification utilizing two single stage mixed suspension mixed product removal crystallizers. The first stage was an antisolvent cooling crystallization, providing refined modafinil with >98% yield. The second cooling crystallization delivered crystalline modafinil with >99% purity in the required polymorphic form I suitable for formulation.
Disciplines :
Chemistry
Author, co-author :
Silva Brenes, Diana Vanessa   ;  Université de Liège - ULiège > Département de chimie (sciences) > Center for Integrated Technology and Organic Synthesis ; Crystallization Design Institute, Molecular Sciences Research Center, University of Puerto Rico, San Juan, Puerto Rico
Agrawal, Shailesh  ;  Crystallization Design Institute, Molecular Sciences Research Center, University of Puerto Rico, San Juan, Puerto Rico
López-Mejías, Vilmalí ;  Crystallization Design Institute, Molecular Sciences Research Center, University of Puerto Rico, San Juan, Puerto Rico ; Department of Chemistry, University of Puerto Rico, San Juan, Puerto Rico
Duconge, Jorge;  Department of Pharmaceutical Sciences, University of Puerto Rico, San Juan, Puerto Rico
Vlaar, Cornelis P. ;  Department of Pharmaceutical Sciences, University of Puerto Rico, San Juan, Puerto Rico
Monbaliu, Jean-Christophe   ;  Université de Liège - ULiège > Molecular Systems (MolSys) ; WEL Research Institute, Wavre, Belgium
Stelzer, Torsten  ;  Crystallization Design Institute, Molecular Sciences Research Center, University of Puerto Rico, San Juan, Puerto Rico ; Department of Pharmaceutical Sciences, University of Puerto Rico, San Juan, Puerto Rico
 These authors have contributed equally to this work.
Language :
English
Title :
Continuous flow synthesis and crystallization of modafinil: a novel approach for integrated manufacturing
Publication date :
2024
Journal title :
Reaction Chemistry and Engineering
eISSN :
2058-9883
Publisher :
Royal Society of Chemistry
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
NASA - National Aeronautics and Space Administration
F.R.S.-FNRS - Fonds de la Recherche Scientifique
ULiège - Université de Liège
NSF - National Science Foundation
Funding text :
This study was primarily supported by the National Aeronautics and Space Administration Experimental Program to Stimulate Competitive Research (NASA, 80NSSC19M0148), the F.R.S.-FNRS (Incentive grant for scientific research MIS F453020F, JCMM) and the University of Li\u00E8ge. The Rigaku XtalLAB SuperNova X-ray micro-diffractometer was acquired under the Major Research Instrumentation Program of the National Science Foundation (NSF, CHE-1626103). The authors acknowledge Dr. Aliou Mbodji, a member of the Crystallization Design Institute, for his support in preparing figures.
Available on ORBi :
since 25 September 2024

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