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The Application of a Continuous Grignard Reaction in the Preparation of Fluconazole
Contributor(s):: Korwar, Sudha, Amir, Somi, Tosso, Perrer N., Desai, Bimbisar K., Kong, Caleb J., Fadnis, Swara, Telang, Nakul S., Ahmad, Saeed, Roper, Thomas D., Gupton, B. Frank
The application of continuous methods in the synthesis of active pharmaceutical ingredients continues to receive significant attention in the academic as well as the industrial research communities. One of the major advantages of continuous methods is the ability to safely access kinetic synthons...
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The A Priori Design and Selection of Ionic Liquids as Solvents for Active Pharmaceutical Ingredients
Contributor(s):: Kunov-Kruse, AJ, Weber, CCRogers, RD, Myerson, AS
In this paper we derive a straightforward computational approach to predict the optimal ionic liquid (IL) solvent for a given compound, based on COSMO-RS calculations. These calculations were performed on 18 different active pharmaceutical ingredients (APIs) using a matrix of 210 hypothetical...
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The Application of an Automated Control Strategy for an Integrated Continuous Pharmaceutical Pilot Plant
Contributor(s):: Lakerveld, R, Benyahia, BHeider, PL, Zhang, HT, Wolfe, A, Testa, CJ, Ogden, S, Hersey, DR, Mascia, S, Evans, JMB, Braatz, RD, Barton, PI
Continuous manufacturing offers potential opportunities for the improved manufacturing of pharmaceutical products. A key challenge is the development of an appropriate control strategy. The experimental application of an automated control strategy is presented for an end-to-end continuous...
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Scaling continuous API synthesis from milligram to kilogram: extending the enabling benefits of micro to the plant
Contributor(s):: Berton, M, de, Souza, JMAbdiaj, I, McQuade, DT, Snead, DR
The signature benefits of continuous flow are largely a result of a reactor's micro-sized features. However, as the technology gains industrial traction in the synthesis of active pharmaceutical ingredients (API), the reactors must be scaled to larger size to meet production demands. Often, the...
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Process Modeling Issues in the Design of a Continuous-Flow Process for the Production of Ibuprofen
Contributor(s):: Tripodi, A, Martinazzo, RRamis, G, Rossetti, I
The continuous-flow production of active pharmaceutical ingredients is a spreading applicative Research Article field. Process simulation tools are effective means for in silico process design, but care is needed. A paradigmatic example is the synthesis of ibuprofen. First, the most appropriate...
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Process Analytical Technology for Crystallization of Active Pharmaceutical Ingredients
Contributor(s):: Malwade, CR, Qu, HY
Background: Pharmaceutical industry is witnessing increased pressure to introduce innovative and efficient processes for manufacturing Active Pharmaceutical Ingredients (APIs) in order to be competitive as well as to meet the stringent product quality requirements set by regulatory authorities....
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Micro reactor and flow chemistry for industrial applications in drug discovery and development
Contributor(s):: Baraldi, PT, Hessel, V
In this review, case studies focused on syntheses of active pharmaceutical ingredients, intermediates and lead compounds are reported employing micro reactors and continuous flow technology in areas such as medicinal chemistry, chemical development and manufacturing. The advantages of flow...
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Mechanochemistry Can Reduce Life Cycle Environmental Impacts of Manufacturing Active Pharmaceutical Ingredients
Contributor(s):: Galant, O, Cerfeda, GMcCalmont, AS, James, SL, Porcheddu, A, Delogu, F, Crawford, DE, Colacino, E, Spatari, S
The scale-up of mechanochemical methods could play a transformative role in making manufacturing processes in the pharmaceutical industry greener by eliminating solvent use and recovery. Combined with energy-efficient continuous processing that consolidates reaction steps, mechanochemistry's...
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Integrated Flow Processing - Challenges in Continuous Multistep Synthesis
Contributor(s):: Pieber, B, Gilmore, K, Seeberger, PH
The way organic multistep synthesis is performed is changing due to the adoption of flow chemical techniques, which has enabled the development of improved methods to make complex molecules. The modular nature of the technique provides not only access to target molecules via linear flow...
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Forbidden Chemistries - Paths to a Sustainable Future Engaging Continuous Processing
Contributor(s):: Gutmann, B, Kappe, CO
Optimizing current chemical processes alone does not yield the improvements required in the fine chemical and pharmaceutical industries. At least partially, a switch from batch to continuous manufacturing is needed. Cost-, time-, and atom-efficient routes frequently demand the application of high...
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Flow Processing as a Tool for API Production in Developing Economies
Contributor(s):: de;Souza, ROMA, Watts, P
In this perspective article, the use of continuous flow synthesis to prepare advanced pharmaceutical intermediates in developing economies is highlighted. Case studies are presented to suggest that cost effective local manufacture of life saving drugs, may potentially be implemented to facilitate...
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Design Space Identification and Visualization for Continuous Pharmaceutical Manufacturing
Contributor(s):: Diab, S, Gerogiorgis, DI
Progress in continuous flow chemistry over the past two decades has facilitated significant developments in the flow synthesis of a wide variety of Active Pharmaceutical Ingredients (APIs), the foundation of Continuous Pharmaceutical Manufacturing (CPM), which has gained interest for its...
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Control of Pharmaceutical Cocrystal Polymorphism on Various Scales by Mechanochemistry: Transfer from the Laboratory Batch to the Large-Scale Extrusion Processing
Contributor(s):: Stolar, T, Lukin, STireli, M, Sovic, I, Karadeniz, B, Kerekovic, I, Matijasic, G, Gretic, M, Katancic, Z, Dejanovic, I, di, Michiel, M, Halasz, I, Uzarevic, K
We demonstrate a controllable mechanochemical synthesis of cocrystal polymorphs of ascorbic acid (vitamin C) and nicotinamide (vitamin B3) on different scales and without using bulk solvents. Next to the previously described polymorph of the 1:1 cocrystal, which is one of the first cocrystals...
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Continuous purification of active pharmaceutical ingredients using multistage organic solvent nanofiltration membrane cascade
Contributor(s):: Peeva, L, Burgal, JDValtcheva, I, Livingston, AG
Downstream processing accounts for a large fraction of the production costs in pharmaceutical manufacturing. Organic solvent nanofiltration performed in a membrane cascade offers an interesting possibility for a continuous downstream processing unit operation. This work demonstrates continuous...
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Characterization of Near-Infrared and Raman Spectroscopy for In-Line Monitoring of a Low-Drug Load Formulation in a Continuous Manufacturing Process
Contributor(s):: Harms, Zachary, Shi, Zhenqi: Kulkarni, Rajesh, Myers, David P.
Reflectance spectroscopy is an excellent candidate for process analytical technology (PAT) applications in continuous manufacturing of pharmaceutical tablets. Spectroscopic methods provide a real-time, nondestructive measurement of the active pharmaceutical ingredient (API) concentration in order...
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Bachem - Insights into Peptide Chemistry Achievements by the World's Leading Independent Manufacturer of Peptides
Contributor(s):: Mergler, M, Loidl, GDiekmann, M, Dick, F
The Swiss fine chemicals company Bachem, pioneer and specialist in the chemical synthesis of peptides, has also become an internationally leading manufacturer of peptide active pharmaceutical ingredients (APIs). In response to increasing demands in scale and purity, Bachem's Research Article...
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Assessing the Greenness of Mechanochemical Processes with the DOZN 2.0 Tool br
Contributor(s):: Sharma, P, Vetter, CPonnusamy, E, Colacino, E
As the demand increases for more sustainable chemical production,mechanochemical processes have been proposed as greener alternatives to traditional manufacturing methods. To support the transition to mechanochemical processes,quantitative assessment methods must be developed to measure and...
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Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing
Contributor(s):: Zhang, P, Weeranoppanant, NThomas, DA, Tahara, K, Stelzer, T, Russell, MG, O'Mahony, M, Myerson, AS, Lin, HK, Kelly, LP, Jensen, KF, Jamison, TF, Dai, CH, Cui, YQ, Briggs, N, Beingessner, RL, Adamo, A
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...
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A systematic reactor design approach for the synthesis of active pharmaceutical ingredients
Contributor(s):: Emenike, VN, Schenkendorf, R, Krewer, U
Today's highly competitive pharmaceutical industry is in dire need of an accelerated transition from the drug development phase to the drug production phase. At the heart of this transition are chemical reactors that facilitate the synthesis of active pharmaceutical ingredients (APIs) and whose...