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Organophotocatalytic N-Demethylation of Oxycodone Using Molecular Oxygen
Contributor(s):: Chen, Yuesu, Glotz, GabrielCantillo, David, Kappe, C. Oliver
N-Demethylation of oxycodone is one of the key steps in the synthesis of important opioid antagonists like naloxone or analgesics like nalbuphine. The reaction is typically carried out using stoichiometric amounts of toxic and corrosive reagents. Herein, we present a green and scalable...
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Development of a Green and Sustainable Manufacturing Process for Gefapixant Citrate (MK-7264) Part 4: Formylation–Cyclization as a Flow–Batch Process Leads to Significant Improvements in Process Mass Intensity (PMI) and CO Generated versus the Batch–
Contributor(s):: Otte, Douglas A. L., Basu, Kallol, Jellett, Lisa, Whittington, Michael, Spencer, Glenn, Burris, Matthew, Corcoran, Emily B., Stone, Kevin, Nappi, Jarod, Arvary, Rebecca A., Donoghue, David, Ren, Hong, Maloney, Kevin M., Naber, John R.
Gefapixant citrate (MK-7264) is a P2X3 antagonist for the treatment of chronic cough. The second generation manufacturing route developed for the Step 3A/3B formylation–cyclization reaction to generate the key intermediate diaminopyrimidine (1) (AF-072) required a significant excess of ethyl...
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End-to-end continuous flow synthesis and purification of diphenhydramine hydrochloride featuring atom economy, in-line separation, and flow of molten ammonium salts†
Contributor(s):: Snead, David R., Jamison, Timothy F.
A continuous end-to-end synthesis and purification of diphenhydramine hydrochloride featuring atom economy and waste minimization is described. Combining a 1 : 1 molar ratio of the two starting material streams (chlorodiphenylmethane and N,N-dimethylaminoethanol) in the absence of additional...
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E-factor analysis of a pilot plant for end-to-end integrated continuous manufacturing (ICM) of pharmaceuticals
| Contributor(s):: Stephen C. Born, Wei Wu, Khrystyna Shvedova, Ridade Sayin, Bhakti S. Halkude, Federica Casati, Anjana Ramnath, Paul Hermant, Bayan Takizawa, Thomas F. O'Connor, Xiaochuan Yang, Sukumar Ramanujamd, Salvatore Mascia, Christopher J. Testa, Chuntian Hu
Most drugs are still manufactured by time-intensive and cost-inefficient batch processes; however, the pharmaceutical industry is undergoing a transition to continuous processes to benefit from the reduced lead time, cost, and footprint and improved quality associated with this new methodology....
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Process modelling and simulation for continuous pharmaceutical manufacturing of ibuprofen
| Contributor(s):: Jolliffe, HG, Gerogiorgis, DI
Pharmaceutical corporations face rapidly rising process Research Article and development (R&D) as well as production costs due to globalised competition. Batch production processes are dominant in the pharmaceutical industry and have multiple advantages, including equipment flexibility,...
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Process modelling, simulation and technoeconomic evaluation of crystallisation antisolvents for the continuous pharmaceutical manufacturing of rufinamide
| Contributor(s):: Diab, S, Gerogiorgis, DI
Continuous Pharmaceutical Manufacturing (CPM) is a promising new paradigm to produce active pharmaceutical ingredients (APIs), allowing reduced equipment dimensions, lower waste production and energy consumption, and safer operation in comparison to the industrially dominant batch methods....
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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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Metabolic Engineering: The Ultimate Paradigm for Continuous Pharmaceutical Manufacturing
| Contributor(s):: Yadav, VG, Stephanopoulos, G
Research Article and development (R&D) expenditures by pharmaceutical companies doubled over the past decade, yet candidate attrition rates and development times rose markedly during this period. Understandably, companies have begun downsizing their pipelines and diverting investments away from...
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Formation of Ciprofloxacin-Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes-An Investigation into Critical Process Parameters
| Contributor(s):: Karimi-Jafari, M, Ziaee, AO'Reilly, E, Croker, D, Walker, G
The mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to...
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Continuous manufacturing – the Green Chemistry promise?
| Contributor(s):: Klavs F. Jensen
Continuous manufacturing and Green Chemistry, are two promising approaches to synthesis with underutilized potential that are gaining traction by the wider pharmaceutical community. We review Green Chemistry advances resulting when transitioning to continuous manufacturing with focus on Green...