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) × 0.7 meter (length) × 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.
Catalyst deactivation by carbon deposition has been investigated for the dehydrogenation of propane to propene on a Cr 2 O 3 /Al 2 O 3 catalyst. Computational fluid dynamics was used to couple the 3D transport and reaction processes occurring inside the cylindrical pellet to the gas flow around the pellet. The pellet scale reaction and carbon laydown are shown to be strongly affected by the bed scale tube wall heat flux supplied for the endothermic reactions, and the species distributions on the pellet surface are also affected by the ease of reactant access to the particle. The development of particle internal gradients and carbon accumulation are illustrated for the early stages of deactivation. Carbon deposition is initially strongest in the high temperature regions close to the tube wall. As time progresses, the increased deactivation caused by the carbon acts to reduce all rates of reaction, and propene production and coke formation shift to other regions of the pellet.
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