Rapid, green and self-optimised additive manufacturing of medicines

使用传统方法开发口服固体剂量（OSD）产品需要数年时间。这个开发过程不仅费力、耗时，而且对环境也不友好：在广泛的经验驱动的产品开发试验中消耗了宝贵的溶剂、材料和能源。此外，COVID-19大流行还暴露并放大了药品供应链的脆弱性，严重缺乏响应能力，对辅料和药品供应链都产生了影响。该项目旨在通过将增材制造（AM）与自我优化方法相结合，开发一种基本的药物制造新方法，为实现未来药物的快速、反应灵敏、绿色配方和生产平台做出重大贡献。增材制造（例如3D打印）作为药品生产平台，特别是小批量、高价值产品，显示出相当大的前景。AM还具有独特的位置，可以快速修改剂量和药物释放行为，以满足特定患者的要求。在本项目中，将通过优化尺寸、微观结构和工艺设置来调整剂量和药物释放。我们将开发一种自优化方法来加速实验设计和系统优化。类似的方法已用于药物片剂开发的实验设计，以优化配方和工艺参数，与传统的实验设计方法相比，实验工作量减少了60%。正如项目中提出的那样，将AM与自我优化相结合，将使我们能够实现快速，绿色和响应灵敏的制造平台。这个新平台还将使材料-工艺-结构-性能关系的有效探索成为可能，从而使我们对使用增材制造的制药产品数字化设计的理解发生了一步变化。拟议的项目将有助于数字产品设计师，其目标是实现“正确的第一次”制造高质量和稳定的产品。药品生产中的数字工具还将通过减少原材料浪费、能源消耗和溶解测试中溶剂的使用，对环境产生巨大的积极影响。

The development of oral solid dose (OSD) products using traditional approaches takes several years. This development process is not only laborious and time consuming but also environmentally unfriendly: valuable solvents, materials and energy are consumed during extensive empirically driven product development trials. There is also a significant lack of responsiveness and fragility of medicine supply chain was exposed and magnified by the COVID-19 pandemic, impacting both the supply chains of excipients and drugs. This project aims to develop a fundamental new approach to medicines manufacture by combing additive manufacturing (AM) with self-optimisation methods to make a significant contribution towards realising a rapid, responsive, green formulation and production platform for future medicines.AM (e.g. 3D printing) is showing considerable promise as a production platform for medicines, in particular for low-volume, high-value products. AM is also uniquely placed to enable rapid modification of dose and drug release behaviour to meet specific patient requirements. In this project, both dose and drug release will be adjusted through the optimisation of the size, microstructure and process settings. A self-optimisation method will be developed to accelerate experimental design and system optimisation. Similar methods have been used for experimental design in pharmaceutical tablet development to optimise formulation and process parameters, demonstrating a reduction of experimental workload of 60% compared to a traditional design of experiments approach. Coupling AM with self-optimisation, as proposed in the project, will allow us to realise a rapid, green and responsive manufacturing platform. This new platform will also enable the efficient exploration of the material - process - structure - performance relationship, leading to a step change in our understanding in the digital design of pharmaceutical products using AM.The proposed project will contribute to a digital product designer with the goal of enabling a 'right first time' manufacturing of high quality and stable products. Digital tools in drug product manufacturing will also have a drastic positive environmental impact by reducing the waste of raw materials, energy consumption and the use of solvents in dissolution testing.