The Application of Flow Chemistry to Advanced Pharmaceutical Manufacturing

通过在商业组织中采用最新技术和最佳方法来改进工作实践，为公司提供一系列竞争优势，从而使公司受益。在制药、农化和神经药物合成领域，基于Flow化学的工艺制造是一种提高效率和生产力的新方法。流动反应器可以设计成小型化的高性能单元，而不是在大型笨重的反应器中工作，从而使化学品的连续进料能够实时转换，从而产生恒定的产品输出流。事实上，几个反应器可以集成在一起，以允许多步骤转换来制备复杂的产品。这种方法还允许通过简单地让反应器运行更长时间来快速缩放输出，并且可以通过快速启动和关闭来促进及时生产。从概念上讲，这种从旧的基于批次的化学合成到现代的流动化学（一种连续制造的形式）的转变可以比作制作咖啡的演变。从历史上看，咖啡是用炉子加热的渗透器（经典的基于批量的化学合成）制备的，然而，现代的浓缩咖啡机现在可以按下几个按钮，按需制作咖啡，甚至延长了添加香料、牛奶和甜味剂的过程（基于流动的合成）。从药物合成的角度来看，采用Flow Chemistry还可以节省空间、能源和大大提高工人的安全性。提供相当大价值的另一个方面是小尺寸反应器，它易于应用更高的压力和温度，可用于大大加速反应完成，允许更大的材料吞吐量，更高的产量和提高产品的纯度。这样就可以通过减少净化工作流来缩短生产序列。目前，流动化学技术及其相关技术的大部分实用知识都在大学里。在这项提案中，我们打算将这一经验直接应用到企业环境中，将其应用于设计和简化一系列选定的化学制造过程。这将使该公司能够测试并将该技术嵌入其商业产品中。所产生的经验和数据也可以用来通过生成“最佳实践”将这项技术推广给其他组织。

Improving working practices by adopting the latest technologies and best approaches into a commercial organisation benefits the company by providing it with a series of competitive edges. In the areas of pharmaceutical, agrochemical and neuroceuticals synthesis, Flow Chemistry based process manufacturing is a new approach that boosts both efficiency and productivity. Instead of working in large bulky reactors, flow reactors can be engineered as miniaturised high performance units that enable a continuous feed of chemicals to be converted in real-time producing a constant product output stream. Indeed, several reactors can be integrated together to allow multi-step transformations to prepare complex products. This approach also allows rapid scaling of the output by simply leaving the reactor running longer and can facilitate just in time manufacture through rapid start-up and shut down. Conceptually this transition from old Batch based chemical synthesis to modern Flow Chemistry (a form of continuous manufacturing) can be likened to the evolution in making coffee. Historically, coffee was prepared using a stove heated percolator (Classical batch based chemical synthesis) however, modern expresso coffee machines can now, at the press of a few buttons, make coffee on-demand, even extending the process adding flavours, milk and sweeteners (Flow based synthesis). From a pharmaceutical synthesis perspective adopting Flow Chemistry also provides gains with regards saving on space, energy and much improved worker safety. Another aspect which offers considerable value is the small dimension reactors which facilitate easy application of higher pressures and temperatures which can be used to drastically accelerate the reaction to completion allowing much greater throughput of material, higher yields and improved purity of the product. This then can shorten the production sequence by reducing purification work streams. Currently much of the practical knowledge of Flow Chemistry techniques and its associated technologies are resident in Universities. In this proposal we intend to take this experience directly into a corporate environment where it will be applied to design and streamline a series of selected chemical manufacturing processes. This will enable the company to test and embed the technology into its commercial offerings. The experiences and data generated can also be used to spring board this technology to other organisations through the generation of 'best practices'.