Scaling up microreactors for kilogram‐scale synthesis of piperacillin: Experiments and computational fluid dynamics simulations

Abstract

In this study, two membrane dispersion microreactors in series are used to synthesize piperacillin with low impurity content in kilogram scale. By combining experiments and computational fluid dynamics simulations, the membrane size and cross-sectional area are scaled up from 2 mm × 0.7 mm and 2 mm × 1 mm to 6.5 mm × 2.5 mm and 6.5 mm × 3.5 mm, respectively, and the reaction time is extended from~10 tõ 60 min, which achieves that the synthesis scale of each batch is increased from 15 g to 1 kg. Subsequently, the effects of distance between ammonia feed and 4-ethyl-2,3-dioxo-1-piperazine carbonyl chloride feed, pH, circulation flow rate, and dispersed phase flow rate on solution concentration are discussed. The final piperacillin product with an average yield of~94.70%, a purity exceeding 99.7%, the impurity D content~0.077% and E content~0.045%, satisfies the requirements of pharmacopeia regarding antibiotic impurities.

Solar-driven ultrafast lithium extraction from low-grade brine using microfluidics-mediated vortex in scalable electrochemical reactors

“…Furthermore, we demonstrated a scale-out strategy for the SMER module and conducted a comprehensive TEA to validate its commercial viability. The recently growing lab-on-a-chip technology [49][50][51] was proposed to scale our Li extraction system from the microgram to kilogram level. We envisioned integrating 100,000 SMERs in series and parallel as a stack while maintaining precise control of the microstructures and ows (inset of Fig.…”

Critical elements: opportunities for microfluidic processing and potential for ESG-powered mining investments

“…136 Often, this means scaling the characteristic channel dimensions to a few mm or, in a few cases, even larger so that meso-flow might be used. [137][138][139][140][141][142] This strategy has been largely adopted by pharmaceutical companies for medicinal flow chemistry. 143,144 One common commercial flow reactor example is the Corning Advanced-Flow Reactor, 41,145 with internal dimensions above the micron range.…”

Coprecipitation Synthesis of Large-Pore-Volume γ-Alumina Nanofibers by Two Serial Membrane Dispersion Microreactors with a Circulating Continuous Phase

“…Above all, it is necessary to enhance mixing and reduce the mass-transfer resistance . In this study, a PB continuous synthesis approach utilizing serial membrane dispersion microreactors with a circular continuous phase was investigated.…”