Analytical Development, Boehringer Ingelheim, Ridgefield, Connecticut, USA.
AAPS PharmSciTech. 2011 Mar;12(1):312-22. doi: 10.1208/s12249-011-9590-5. Epub 2011 Feb 1.
Over the lifecycle of an orally inhaled product (OIP), multi-stage cascade impactor (CI) measurements are used for different purposes and to address different questions. Full-resolution CIs can provide important information during product development and are widely used but are time- and resource-intensive, highly variable, and suboptimal for OIP quality control (QC) testing. By contrast, Efficient Data Analysis (EDA) combined with Abbreviated Impactor Measurement (AIM) systems pertinent either for QC and-possibly-for adult Human Respiratory Tract (pHRT) has been introduced for OIP performance assessment during and post-development. This article summarizes available evidence and discusses a strategy for using either abbreviated or full-resolution CI systems depending on the purpose of the measurement, such that adequate, accurate, and efficient testing of aerodynamic particle size distribution (APSD) of OIPs can be achieved throughout the lifecycle of a product. Under these proposals, a comprehensive testing program should initially be conducted by full-resolution CI in OIP development to ascertain the product's APSD. Subsequently, correlations should be established from the selected AIM CIs to the corresponding full-resolution system, ideally developing specifications common to both techniques. In the commercial phase, it should be possible to release product using AIM/EDA, keeping the full-resolution CI for investigations, change control, and trouble-shooting, thus optimizing resources for APSD characterization throughout the product lifecycle. If an in vitro-in vivo relationship is established and clinically relevant sizes are known, an AIM-pHRT could serve as a quick indicator that clinically relevant fractions have not changed and also, in the management of post-approval changes.
在吸入制剂的整个生命周期中，多级级联撞击器（CI）测量用于不同的目的和解决不同的问题。全分辨率 CI 可以在产品开发过程中提供重要信息，并且被广泛使用，但它们耗时且资源密集，高度可变，对于吸入制剂的质量控制（QC）测试并不理想。相比之下，高效数据分析（EDA）与简化撞击器测量（AIM）系统相结合，无论是用于 QC 还是成人呼吸道（pHRT），都已被引入用于吸入制剂开发期间和之后的性能评估。本文总结了现有证据，并讨论了根据测量目的使用简化或全分辨率 CI 系统的策略，以便在产品的整个生命周期中对吸入制剂的空气动力学粒径分布（APSD）进行充分、准确和高效的测试。根据这些建议，在吸入制剂的开发过程中，应通过全分辨率 CI 进行全面的测试方案，以确定产品的 APSD。随后，应从选定的 AIM CI 到相应的全分辨率系统建立相关性，理想情况下，为两种技术开发共同的规格。在商业阶段，使用 AIM/EDA 放行产品是可行的，将全分辨率 CI 保留用于调查、变更控制和故障排除，从而优化整个产品生命周期中 APSD 特性的资源。如果建立了体外-体内相关性并且已知临床相关粒径，则 AIM-pHRT 可以作为一个快速指标，表明临床相关部分没有发生变化，并且在批准后变更的管理中也是如此。
