Abstract

Additive Manufacturing as a Leading-Edge Technology for Tailor-Made Flow Chemistry Equipment

Heidrun Gruber-Wölfler, Associate Professor, Graz University of Technology

As the complexity of required setups increases, improvements in the (multistep) synthesis of active pharmaceutical ingredients (APIs) demand executing reactions and downstream processes in specially designed equipment. The use of additive manufacturing, also known as 3D printing, is chosen for producing specialized reactors and other equipment at competitive prices in order to respond quickly to the demanding requirements in pharmaceutical production. This work provides several instances of 3D printed devices used for the analysis, synthesis, and crystallization of API precursors in continuous flow, including flow reactors and analytical instruments. Different materials and production methods will be presented based on the specific chemistry and targeted process. For reactions requiring harsh conditions, selective laser melting (SLM) from stainless steel was utilized, while for applications requiring milder reaction conditions, digital light processing (DLP) was employed, using a UV-curable resin. The stainless-steel reactors are tested for use in a calorimeter for continuous flow measurements, the aerobic oxidation of Grignard reagents by molecular oxygen, the analysis of ammonia in organic solvents, obtaining quick mixing in a multistep synthesis of a valsartan precursor, and more. Additionally, we show ceramic structured inserts that were conceptualized in-house, printed using vat photopolymerization (VPP), and utilized for the decarboxylation of cinnamic acids using an immobilized enzyme. Lastly, UV-curable resins-based lab-scale crystallizers modeled after industrial crystallizers will be presented. The solutions presented here demonstrate the benefits of 3D printing in continuous applications, such as flow calorimetry, biocatalytic reactions and continuous crystallization, showcasing excellent productivity and flexibility to the process requirements.