Microreactor design and testing for a Lipase-based biocatalytic flow process

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From a Review of Noble Metal versus Enzyme Catalysts for Glucose Oxidation Under Conventional Conditions Towards a Process Design Analysis for Continuous-flow Operation

A methodology for the ex ante evaluation of different processing options is proposed. Current processes for glucose oxidation and possible improvements using microreactor technology are investigated. As twofold prime research objectives, the oxidation with noble metal catalyst versus enzymatic oxidation and the oxidation under conventional process conditions versus under Novel Process Windows are explored. Operation and design of an active and stable catalyst, reactor performance, and work-up are included. This ex ante analysis gives information of the critical aspects of a process prior to technology development and facilitates the development of new process routes; especially valuable if step and paradigm changing routes are undertaken, with even no vague idea on their performance potential and with high technological risk. The methodology used for gluconic acid production will be transferred to other chemicals which have the potential in using microreactor technology and Novel Process

Recent changes in patenting behavior in micro process technology and its possible use for gas-liquid reactions and the oxidation of glucose

The miniaturization of continuous processes has been of increasing interest in the past decade, and microreaction technology and flow chemistry have moved from academic and industrial research to commercial applications. With industry taking up such innovations, this trend is also reflected in the patenting behavior of companies active in this area. This review is a continuation of the review paper on microreactor patents published by Hessel et al. and indicates major changes in patenting trends since 2006. Moreover, a different patent database search algorithm is presented, which complements the algorithm explained in the previous review. In addition, the preservation of intellectual property is analyzed for multiphase reactions and particularly solid-catalyzed gas–liquid reactions in microreactors, which play an important role in the chemical and pharmaceutical industries and are reactions that benefit largely from microprocessing. Among other results, we show that the number of patents has increased in this field, with solid-catalyst design and deposition, control of the flow pattern, and ensured stable flow as the main challenges

Microreactor design and testing for a Lipase-based biocatalytic flow process

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Lipase-based biocatalytic flow process in a packed-bed microreactor

The transesterification of ethyl butyrate with 1-butanol to give butyl butyrate catalyzed by Novozym 435 was performed in a batch slurry reactor and in a packed-bed microreactor. The observed reaction rate is strongly influenced by external and intra-particle transport limitations. However, the packed-bed microreactor allows for higher specific enzyme loading and shorter diffusion pathway than that of the batch reactor, therewith enabling higher overall conversion and higher reaction rate per unit of catalyst volume. Novozym 435 showed to be stable up to 80 °C in the packed-bed microreactor, with low reactant molar ratio (ethyl butyrate:1-butanol) being desirable to achieve higher conversions. Total conversion was achieved in approximately 4 min residence time giving 0.04 mol/L of product, while in batch more than 30 min were needed for maximum conversion of 87%. Continuous 12 h operation at 70 °C was performed without noticeable deactivation of the enzymes. Moreover, the same packing was reused for several days without indicating any activity loss. To the best of our knowledge, this is the first engineering paper on enzymatic microreactors that gives a complete kinetic description, clear-cut benchmarking to a batch process, study on enzyme stability, and an outline on enzymatic microreactor production performance

Eco-efficiency analysis for intensified production of an active pharmaceutical ingredient : a case study

This article presents results on cost and performance benefit analysis of optimization and intensification activities of a pharmaceutical process. A batch process for the production of a low-volume, high value active pharmaceutical ingredient, developed at Sanofi (France), has been used as a case study. With the scale of 100 kg/y and a product price of a few thousands Euros per kilogram, also following a general trend in pharmaceutical industry, this process is supposed to be an ideal candidate for continuous, modular plant production of a highly potent drug. It was aimed to keep the learning gathered generic, i.e. to stand for the whole class of similarly produced drugs. The impact of various chemical process parameters on the overall production costs has been investigated and process performance represented in terms of operation time, waste and resource usage as the main process metrics. Five optimized and intensified scenarios were compared to the reference case operated at a Sanofi site: intensified reaction, continuous processing, alternative catalysts, change of solvent, change in the purification sequence, recovery of the key product, and intensified drying option. The analysis has shown that, under the assumptions used, an intensified millireactor based process with a subsequent continuous post-processing brings the most benefits in terms of cost, while its process performance, although equal or slightly better than batch, still can be optimized. The total product cost is then reduced for 35 %, while the operating time is 27 % lower than the base case, with 47 % less labor needed compared to the reference case. First studies on ecological impact by University of Jena confirm these promising findings and are presented in outlines herein; with an own paper on respective details to follow. The results are now undergoing experimental validation in the newly developed compact container plant of Evonik