Digital Design and Manufacture of Amorphous Pharmaceuticals (DDMAP)

非晶态药物数字化设计与制造中心(DDMAP)将建立一项新的国际合作，汇聚来自英国(斯特拉斯克莱德大学)、丹麦(哥本哈根大学)和比利时(根特大学)的世界领先的研究人员小组，使人们对非晶态材料的基本认识发生重大变化，以便应用于药品制造中真正的工业挑战。非晶态材料不同于药物中常用的晶态材料，为解决当前产品中的挑战提供了大量机会，包括改进加工、稳定性和患者的整体性能。该中心将解决支持非晶态分子固体在药物开发和制造中的选择、生产和应用的关键研究问题。研究分为四个工作包，WP1-4：WP1将建立一个独特的无定形药物数据库(APDB)，作为一个研究平台，在整个项目中共享数据，为模型开发提供信息，并与更广泛的社区传播数据。具体的研究目标包括建立药物分子的预测性无定形稳定性指数(ASI)，并利用X射线PDF、建模和精化方法等技术研究无定形药物以及共无定形和药物-聚合物体系的固态结构。这项工作将使我们能够更好地了解这些材料的行为以及如何在制造过程中最好地利用它们。WP2将开发预测方法和工具，用于通过热熔融挤压(HME)进行正确的首次非晶态药物加工，施加热和压力以熔化材料的过程，以及后续的剂型加工步骤，包括压缩和3D打印。该团队将利用所有三个合作伙伴以及通过强大的x射线提供的先进的连续加工和分析能力，研究非晶态材料在研磨、压实、干燥和添加剂制造等关键二次加工步骤中的转化和稳定性。WP3将研究非晶态制剂在生物悬浮介质(例如模拟胃液和肠液)中的药物释放机制和结构变化，以开发非晶态固体制剂在患者中的性能预测模型。借助WP1和W2的进展，国际合作伙伴广泛的溶解和分析能力将确定药物释放机制和使用过程中系统中发生的物理变化。我们将修改组成和结构以实现对版本的控制。WP4将由项目团队管理，通过共享数据、培训、最佳实践和学习来加强研究人员和合作伙伴之间的合作。各中心之间的流动和知识交流将通过教职人员和研究人员之间的面对面进展会议轮流轮换来促进。将利用定期虚拟会议就计划达成一致并跟踪进展情况。数字工具(MIRO、电子实验室笔记本-ELN)和数据管理计划将确保在DDMAP中持续进行交流，而数字交流计划将确保与国际学术界和工业界及时传播产出和成果。纳入WP1-3产出的工业案例研究将通过网络、社交媒体和虚拟活动在全球传播和推广，预计将根据目前的网络覆盖范围分析扩大到数万人。这些例子包括开放获取非晶态材料数据库(APDB)和获取开发的非晶态索引工具。

The Digital Design and Manufacture of Amorphous Pharmaceuticals (DDMAP) Centre will create a new international collaboration bringing together a world-leading group of researchers from the UK (University of Strathclyde), Denmark (University of Copenhagen) and Belgium (Ghent University) to deliver a step change in fundamental understanding of amorphous materials in order to apply to real industrial challenges in medicines manufacturing. Amorphous materials are different from the crystalline materials commonly used in medicines and offer substantial opportunities to address challenges in current products including improved processing, stability and overall performance in patients.The centre's will address key research questions that underpin the selection, production and application of amorphous molecular solids in medicines development and manufacture. Research is split across four work packages, WP1-4:WP1 will establish a unique Amorphous Pharmaceuticals Database (APDb) as a research platform to share data across the project, inform model development and disseminate data with the wider community. Specific research aims include establishing a predictive Amorphous Stability Index (ASI) for drug molecules and to investigate the solid-state structure of amorphous drugs as well as co-amorphous and drug-polymer systems using techniques including X-ray PDF, modelling and refinement approaches. This work will allow us to better understand how these materials behave and how best to exploit them in manufacturing processes.WP2 will develop predictive methodologies and tools for right-first-time amorphous pharmaceutical processing via Hot Melt Extrusion (HME), the process of applying heat and pressure to melt a material, and subsequent dose form processing steps including compression and 3D printing. The team will exploit advanced continuous processing and analytical capabilities available across all three partners and through powerful x-rays, to investigate transformations and stability of amorphous materials during key secondary processing steps such as milling, compaction, drying and additive manufacturing.WP3 will investigate the mechanisms and structural changes of drug release from amorphous dosage forms in biorelevant media, e.g. that simulate stomach and intestinal fluids, to develop models for performance prediction of amorphous solid dosage forms in patients. Drawing on progress in WP1 and 2 the extensive dissolution and analytical capabilities across the international partners will identify drug release mechanisms and physical transformations that occur in systems during use. We will modify composition and structure to achieve control over release.WP4 will be managed by the project team to strengthen collaboration across the researchers and partners through sharing data, training, best practices and learning. Mobility and knowledge exchange between centres will be promoted through Faculty and Researcher exchanges with face-to-face progress meetings rotating round centres. Regular virtual meetings will be used to agree plans and track progress. Digital tools (MIRO, Electronic Laboratory Notebooks - ELN) and data management plans will ensure ongoing comms across DDMAP and a digital comms plan will ensure timely dissemination of outputs and outcomes with the international academic and industrial communities. Industrial case studies that integrate outputs from WP1-3 will be disseminated and promoted globally through networks, social media and virtual events anticipated to outreach to tens of thousands based on current network reach analytics. These include examples such as an open access database for amorphous materials (APDb) and access to developed amorphous indexing tool.