Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, 10903 New Hampshire Ave., Silver Spring, MD 20993, United States.
Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, 10903 New Hampshire Ave., Silver Spring, MD 20993, United States.
Int J Pharm. 2019 Oct 5;569:118551. doi: 10.1016/j.ijpharm.2019.118551. Epub 2019 Jul 20.
The purpose of this study is to establish a material library and discuss its potential application to the development and lifecycle management of a continuous manufacturing process for solid dosage forms. Particularly, this study addresses the importance of selecting process-relevant testing conditions for material characterization, proposes a methodology to capture relevant information with a reduced set of measurements, and correlates material properties with process performance. This study included 20 pharmaceutical materials, and each material was characterized by 44 properties, capturing 880 data points. The stress conditions of a commonly used feeder hopper were calculated using the Janssen model for six selected materials. Multivariate analysis, such as principal component analysis and clustering analysis, was used to explore the knowledge space of the material library. Statistically similar and dissimilar material properties were evaluated for material feeding performance from a loss-in-weight feeder to test utility of the material library. 20 materials included in this study show a wide range of material properties. Consolidation stress during testing significantly impacts obtained material properties. Based on a material similarity metric, a reduced set of characterization tests that captures >95% of the relevant information was identified. Materials were then grouped into six clusters. The material loss-in-weight feeding results show that the materials within the same cluster show similar feeding performance, while selected materials from different cluster have different feeding performance. Additional material understanding regarding flow properties may be needed to implement a continuous manufacturing process. Characterization using multiple tests under process-relevant conditions can be helpful to establish the correlation between material properties and process and product performance using multivariate analysis tools.
本研究旨在建立一个材料库，并探讨其在固体制剂连续制造工艺的开发和生命周期管理中的潜在应用。特别是，本研究强调了选择与工艺相关的测试条件进行材料特性描述的重要性，提出了一种方法，通过减少测量次数来获取相关信息，并将材料特性与工艺性能相关联。本研究包括 20 种药物材料，每种材料的特性由 44 个参数描述，共获得 880 个数据点。使用 Janssen 模型计算了六种选定材料的常用给料斗的应力条件。使用多元分析，如主成分分析和聚类分析，来探索材料库的知识空间。统计上相似和不同的材料特性用于从失重给料器评估材料的给料性能，以检验材料库的实用性。本研究中包括的 20 种材料表现出广泛的材料特性。测试过程中的固结应力对获得的材料特性有显著影响。基于材料相似性度量，确定了一组可捕获>95%相关信息的简化特征测试。然后将材料分为六个组。材料失重给料结果表明，同一组内的材料具有相似的给料性能，而来自不同组的选定材料具有不同的给料性能。可能需要进一步了解有关流动性能的材料知识，以实施连续制造工艺。使用多元分析工具，通过在与工艺相关的条件下进行多项测试进行特性描述，有助于建立材料特性与工艺和产品性能之间的相关性。
