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Continuous Synthesis of Active Pharmaceutical Ingredients with In-House Designed 3D Printed Reactors

Thursday, 10 September 2020 at 09:30

Add to Calendar ▼2020-09-10 09:30:002020-09-10 10:30:00Europe/LondonContinuous Synthesis of Active Pharmaceutical Ingredients with In-House Designed 3D Printed ReactorsMicrofluidics and Flow Chemistry Europe 2020 in Rotterdam, The NetherlandsRotterdam, The NetherlandsSELECTBIOenquiries@selectbiosciences.com

Continuous manufacturing has become increasingly attractive for the pharmaceutical industry, owing to the diverse benefits of continuous flow technology including fast heat and mass transfer, reduced waste generation, constant product quality and increased safety. Syntheses of active pharmaceutical ingredients (APIs) in a continuous process often involve new complex reactions, which are facilitated by the exploitation of Novel Process Windows concerning temperatures, pressures and concentrations. Consequently, tailor-made reactors are required to achieve optimal and controlled reaction conditions for selective product formation. An advantageous method for the quick and low-cost manufacturing of customized reactors is additive manufacturing, commonly known as 3D printing [5]. Taking up this approach, we designed and produced a number of different reactors utilizing active and passive mixing principles. Two production methods were used based on the needed chemical environments. Additive manufacturing of stainless steel via selective laser melting (SLM) was used for harsh conditions, while a UV-curable resin, processed via digital light processing (DLP), was used for milder reaction conditions. After characterization and assessment of their mixing performance, selected reactors were implemented into continuous setups for the formation of high-value products as well as API precursors. Besides the continuous aerobic oxidation of Grignard reagents to the corresponding phenols using different reactor types, a 3D printed split-and-recombine reactor was employed for achieving efficient mixing in a three-step cascade for the synthesis of a valsartan precursor in continuous flow. The final example deals with an enzymatic decarboxylation reaction in a multipurpose continuous stirred tank reactor, which led to the formation of resveratrol derivatives after a Pd-catalyzed Heck cross-coupling. In summary, in our work we demonstrate the high potential of 3D printing technology for the cost- and time-efficient production of custom-built reactors, applicable for the synthesis of relevant biologically active chemicals in continuous flow.