Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations
Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations
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DOI：
10.1039/c7me00096k
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发表时间：
2018-06-01
影响因子：
3.6
通讯作者：
Florence, Alastair J.
中科院分区：
文献类型：
--
作者：
Brown, Cameron J.;McGlone, Thomas;Florence, Alastair J.
连续制造广泛用于商品的生产。目前，它正吸引制药业和监管机构越来越多的兴趣，作为一种提供稳定药品供应的手段。结晶是大多数药物分离的关键操作，并且已经使用一系列加工技术和规模以连续方式对许多化合物进行了证明。虽然结晶和连续工艺的基本设计原理是已知的，但在具有上市速度和有限材料可用性的相关约束的快速制药工艺开发的背景下应用这些原理是具有挑战性的。连续结晶工艺设计需要系统方法，以避免在工艺的一个方面做出的决定导致结晶或另一单元操作的后续开发步骤更加困难的风险。为了应对这一行业挑战，开发了一种创新的全系统决策方法，以支持快速、系统和高效的连续籽晶冷却结晶工艺设计。对于连续结晶，目标是开发和操作一种稳健、一致的工艺，并严格控制颗粒属性。在这里，提出了一个创新的基于系统的工作流程，以应对这一挑战。的目的，方法，关键决策和输出在每个阶段的定义和案例研究，展示了成功的应用工作流程的快速设计的过程，以生产公斤数量的产品具有独特的，指定的属性适合于药物开发环境。这项工作的结论与未来的应用程序的工作流程，在持续的生产开发，以实现快速的性能为基础的设计药物的愿景。
Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of the majority of pharmaceuticals and has been demonstrated in a continuous manner on a number of compounds using a range of processing technologies and scales. Whilst basic design principles for crystallisations and continuous processes are known, applying these in the context of rapid pharmaceutical process development with the associated constraints of speed to market and limited material availability is challenging. A systematic approach for continuous crystallisation process design is required to avoid the risk that decisions made on one aspect of the process conspire to make a later development step or steps, either for crystallisation or another unit operation, more difficult. In response to this industry challenge, an innovative system-wide approach to decision making has been developed to support rapid, systematic, and efficient continuous seeded cooling crystallisation process design. For continuous crystallisation, the goal is to develop and operate a robust, consistent process with tight control of particle attributes. Here, an innovative system-based workflow is presented that addresses this challenge. The aim, methodology, key decisions and output at each at stage are defined and a case study is presented demonstrating the successful application of the workflow for the rapid design of processes to produce kilo quantities of product with distinct, specified attributes suited to the pharmaceutical development environment. This work concludes with a vision for future applications of workflows in continuous manufacturing development to achieve rapid performance based design of pharmaceuticals.