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、农用化学品和神经性药物合成领域，基于流动化学的流程制造是一种提高效率和生产率的新方法。流动反应堆不是在大型笨重的反应堆中工作，而是可以设计成微型高性能单元，使连续的化学品进料能够实时转化，产生稳定的产品输出流。事实上，可以将几个反应堆集成在一起，以允许进行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堆运行更长时间来快速调整产量，并通过快速启动和关闭来促进及时制造。从概念上讲，从旧的基于批次的化学合成到现代流动化学(一种连续制造的形式)的转变可以比作煮咖啡的进化。在历史上，咖啡是用炉子加热的渗滤器(基于经典批次的化学合成)来调制的，然而，现代的浓缩咖啡机现在只需按几个按钮，就可以根据需要制作咖啡，甚至可以扩展添加香料、牛奶和甜味剂的过程(基于流程的合成)。从药物合成的角度来看，采用流动化学还可以节省空间和能源，并大大提高工人的安全。另一个提供可观价值的方面是小型反应器，它便于轻松应用更高的压力和温度，可用于极大地加速反应直至完成，从而允许更大的材料吞吐量、更高的产率和更高的产品纯度。这可以通过减少提纯工作流来缩短生产顺序。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。在这份提案中，我们打算将这一经验直接带入企业环境，在那里它将被应用于设计和简化一系列选定的化学制造工艺。这将使该公司能够测试这项技术，并将其嵌入其商业产品中。产生的经验和数据也可以用来通过产生“最佳实践”将这项技术推广到其他组织。

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'.