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。这一开发过程不仅费时费力，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，会消耗宝贵的溶剂、材料和能源。此外，药品供应链也明显缺乏响应能力，药品供应链的脆弱性因新冠肺炎疫情而暴露和放大，对赋形剂和药品供应链都产生了影响。这个项目旨在通过将添加剂制造(AM)与自我优化方法相结合来开发一种基本的新药物制造方法，为实现快速、灵敏、绿色的未来药物配方和生产平台做出重大贡献。AM(例如3D打印)作为药物生产平台显示出巨大的前景，特别是对于小批量、高价值的产品。AM也是独一无二的，能够快速修改剂量和药物释放行为，以满足特定患者的要求。在该项目中，将通过优化尺寸、微结构和工艺设置来调整剂量和药物释放。将开发一种自我优化方法，以加快实验设计和系统优化。类似的方法也被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%。将AM与项目中提出的自我优化相结合，将使我们能够实现快速、绿色和响应的制造平台。这一新平台还将使我们能够有效地探索材料-工艺-结构-性能的关系，导致我们对使用AM进行药品数字化设计的理解发生重大变化。拟议的项目将有助于培养一名数字化产品设计师，目标是能够在第一时间制造出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的浪费、能源消耗和溶出度测试中溶剂的使用，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.