Institute of Energy and Process Systems Engineering, Technische Universität Braunschweig, Franz-Liszt-Straße 35, 38106 Braunschweig, Germany; PVZ-Center of Pharmaceutical Engineering, Franz-Liszt-Straße 35A, 38106 Braunschweig, Germany; International Max Planck Research School for Advanced Methods in Process and Systems Engineering, Sandtorstraße 1, 39106 Magdeburg, Germany.
Institute of Energy and Process Systems Engineering, Technische Universität Braunschweig, Franz-Liszt-Straße 35, 38106 Braunschweig, Germany; PVZ-Center of Pharmaceutical Engineering, Franz-Liszt-Straße 35A, 38106 Braunschweig, Germany.
Eur J Pharm Biopharm. 2018 May;126:75-88. doi: 10.1016/j.ejpb.2017.05.007. Epub 2017 May 20.
Today's highly competitive pharmaceutical industry is in dire need of an accelerated transition from the drug development phase to the drug production phase. At the heart of this transition are chemical reactors that facilitate the synthesis of active pharmaceutical ingredients (APIs) and whose design can affect subsequent processing steps. Inspired by this challenge, we present a model-based approach for systematic reactor design. The proposed concept is based on the elementary process functions (EPF) methodology to select an optimal reactor configuration from existing state-of-the-art reactor types or can possibly lead to the design of novel reactors. As a conceptual study, this work summarizes the essential steps in adapting the EPF approach to optimal reactor design problems in the field of API syntheses. Practically, the nucleophilic aromatic substitution of 2,4-difluoronitrobenzene was analyzed as a case study of pharmaceutical relevance. Here, a small-scale tubular coil reactor with controlled heating was identified as the optimal set-up reducing the residence time by 33% in comparison to literature values.
当今竞争激烈的制药行业迫切需要加速从药物开发阶段过渡到药物生产阶段。在这个过渡过程的核心是化学反应器，它促进了活性药物成分（API）的合成，其设计可以影响后续的处理步骤。受此挑战启发，我们提出了一种基于模型的系统反应器设计方法。该概念基于基本过程功能（EPF）方法，从现有最先进的反应器类型中选择最佳的反应器配置，或者可能导致新型反应器的设计。作为概念性研究，这项工作总结了将 EPF 方法应用于 API 合成领域最佳反应器设计问题的基本步骤。实际上，用亲核芳香取代 2,4-二氟硝基苯作为药物相关性的案例研究进行了分析。在这里，确定了带有控制加热的小型管式线圈反应器作为最佳设置，与文献值相比，将停留时间缩短了 33%。
