Division of Pharmaceutical Analysis, Food and Drug Administration CDER, OPS, St. Louis, Missouri, USA.
Pharm Res. 2012 Nov;29(11):3122-30. doi: 10.1007/s11095-012-0804-7. Epub 2012 Jul 3.
To determine if cascade impactor (CI) measurement of drug in small particles from aqueous nasal sprays, described in FDA's 2003 draft Nasal Bioavailability/Bioequivalence Guidance, can be optimized to reduce measurement variability. To examine the influence of flow rate configurations and number of impactor stages on CI deposition and explore the importance of inlet volume.
A total of eight assemblies and manual vs. automatic actuation were tested for deposition on the sum of all stages of the CI, and for Group 2 total drug mass per the Guidance. Mean deposition and variance about the mean were determined for each assembly.
The path length for a spherical 1 l inlet was too short to allow adequate aerosol formation. Data variance was reduced by a factor of two or more by using an automatic actuator relative to manual actuation. Impactor assembly modification did not improve variance over the standard assembly.
Use of a spherical inlet (≥ 2 l volume) and automatic actuation are recommended for comparative measurements of drug in small particles arising from aqueous nasal sprays. The standard (8-stage) 28.3 lpm CI flow rate configuration is recommended when using the Andersen Cascade Impactor (ACI), as no other assembly showed a distinct advantage.
确定美国食品和药物管理局 2003 年鼻腔生物利用度/生物等效性指南草案中描述的用于从小容量水性鼻腔喷雾剂的小颗粒中测定药物的级联撞击器（CI）测量是否可以优化以减少测量变异性。考察流率配置和撞击器级数对 CI 沉积的影响，并探讨入口体积的重要性。
对总沉积在 CI 所有级数上的总和以及根据指南的第 2 组总药物质量，对 8 种组件和手动与自动启动进行了沉积测试。确定了每个组件的平均沉积量和平均值的方差。
对于球形 1 l 入口，其路径长度太短，无法充分形成气溶胶。与手动启动相比，使用自动启动可将数据方差降低两个或更多数量级。相对于标准组件，撞击器组件的修改并未降低方差。
建议在比较水性鼻腔喷雾剂中小颗粒药物时使用球形入口（≥2 l 体积）和自动启动。当使用安德森级联撞击器（ACI）时，建议使用标准（8 级）28.3 lpm CI 流率配置，因为没有其他组件具有明显的优势。
