Digital Design and Manufacture of Amorphous Pharmaceuticals (DDMAP)

无定形药物的数字化设计与制造（DDMAP）

• 批准号: EP/W003295/1
• 负责人: Alastair Florence
• 金额: $ 159.49万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW003295%2F1
• 关键词: Digital; Design; Manufacture; Amorphous; Pharmaceuticals

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.

非晶态药物的数字设计和制造（DDMAP）中心将创建一个新的国际合作，汇集来自英国（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）的世界领先的研究小组，以提供对非晶态材料的基本理解的一个步骤改变，以便应用于药物制造中的实际工业挑战。非晶材料不同于药物中常用的晶体材料，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。该中心将解决在药物开发和制造中支持非晶分子固体的选择、生产和应用的关键研究问题。研究分为四个工作包，WP1-4:WP1将建立一个独特的非晶药物数据库（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非晶态稳定性指数（ASI），并使用包括x射线PDF，建模和改进方法在内的技术研究非晶态药物以及共非晶态和药物-聚合物系统的固态结构。这项工作将使我们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，通过热熔挤压（HME）进行首次非晶态药物加工，应用热量和压力熔化材料的过程，以及随后的剂量形式加工步骤，包括压缩和3D打印。该团队将利用所有三个合作伙伴提供的先进的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（如铣削、压实、干燥和增材制造）中的转变和稳定性。WP3将研究药物在生物相关介质（如模拟胃液和肠液）中从非晶态剂型释放的机制和结构变化，以建立非晶态固体剂型在患者体内的性能预测模型。利用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期间系统中发生的物理变化。我们将修改组成和结构来实现对释放的控制。WP4将由项目团队管理，通过共享数据、培训、最佳实践和学习，加强研究人员和合作伙伴之间的协作。中心之间的流动性和知识交流将通过教师和研究人员交流，面对面的进展会议轮流举行。定期的虚拟会议将用于商定计划和跟踪进展。数字工具（MIRO，电子实验室笔记本- ELN）和数据管理计划将确保整个DDMAP的持续通信，数字通信计划将确保与国际学术界和工业界及时传播产出和成果。整合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范围内传播和推广，根据目前的网络覆盖分析，预计将有数万人参与。这些例子包括非晶材料的开放存取数据库（APDb）和开发的非晶索引工具。