Digital Design and Manufacture of Amorphous Pharmaceuticals (DDMAP)

无定形药物的数字化设计和制造（DDMAP）中心将创建一个新的国际合作，汇集了来自英国（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，以实现对无定形材料的基本理解的一步变化，以应用于药品制造中的真实的工业挑战。无定形材料不同于药物中常用的晶体材料，为解决当前产品的挑战提供了巨大的机会，包括改善加工、稳定性和患者的整体性能。该中心将解决药物开发和制造中无定形分子固体的选择、生产和应用的关键研究问题。研究分为四个工作包，WP 1 -4：WP 1将建立一个独特的无定形药物数据库（APDb）作为研究平台，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），并使用包括X射线PDF，建模和改进方法在内的技术研究无定形药物以及共无定形和药物聚合物系统的固态结构。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。WP 2将开发预测方法和工具，用于通过热熔挤出（HME）进行正确的第一次无定形药物加工，这是一个应用热和压力熔化材料的过程，以及随后的剂型加工步骤，包括压缩和3D打印。该团队将利用所有三个合作伙伴的先进连续处理和分析能力，并通过强大的X射线，研究非晶材料在关键的二次加工步骤（如研磨，压实，干燥和增材制造）中的转化和稳定性。WP 3将研究药物在生物相关介质中从非晶剂型释放的机制和结构变化，例如模拟胃液和肠液，以开发用于预测患者中无定形固体剂型的性能的模型。利用WP 1和WP 2的进展，国际合作伙伴的广泛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转化。我们将修改组成和结构，以实现对发布的控制。WP 4将由项目团队管理，通过共享数据、培训、最佳实践和学习，加强研究人员和合作伙伴之间的合作。中心之间的流动和知识交流将通过教师和研究人员的交流与面对面的进展会议轮流中心。将定期举行虚拟会议，以商定计划和跟踪进展情况。数字化工具（MIRO，电子实验室笔记本- ELN）和数据管理计划将确保整个DDMAP的持续沟通，数字沟通计划将确保及时传播国际学术界和工业界的产出和成果。将通过网络、社交媒体和虚拟活动在全球范围内传播和推广整合了WP 1 -3产出的工业案例研究，根据目前的网络覆盖分析，预计这些研究将覆盖数万人。其中包括非晶材料开放存取数据库（APDb）和开发的非晶索引工具。

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.