Applied Particle Principles LLC, 17347 Westham Estates Court, Hamilton, Virginia, 20158, USA.
Jolyon Mitchell Inhaler Consulting Services Inc., 1154 St. Anthony Road, London, Ontario, N6H 2R1, Canada.
AAPS PharmSciTech. 2019 Jan 8;20(2):57. doi: 10.1208/s12249-018-1276-9.
The multi-stage inertial cascade impactor is used to determine the mass-weighted aerodynamic particle size distribution (APSD) as a critical quality attribute for orally inhaled products (OIPs). These apparatuses progressively size-fractionate the aerosol passing through a series of stages containing one or more nozzles, by increasing particle velocity. Nozzle sizes for a given multi-nozzle stage can be described collectively by effective diameter ([Formula: see text]), related to the cut-point size, providing the link to aerodynamic diameter. Users undertake stage mensuration periodically to assure that each stage [Formula: see text] remains within the manufacturer's tolerance, but there is no guidance on how frequently such checks should be made. We examine the philosophy that particle size-related specifications of the OIP should determine when an impactor is mensurated. Taking an example of a dry powder inhaler-generated aerosol sampled via a Next Generation Impactor with pre-separator, we find that there are only three critical stages that could have a material effect on the measured APSD specified as four groupings of stages following current regulatory practice. Furthermore, [Formula: see text] for the most critical stage having the smallest nozzle sizes could be relaxed by a factor of four or more before risking an inability to measure the mass fraction of API in the group containing the finest particles to a specification within ± 10% of nominal. We therefore conclude that users should consider letting the specification for APSD performance of an OIP in terms of accepted stage groupings drive the impactor quality requirements and frequency that stage mensuration is undertaken.
多阶段惯性级联撞击器用于确定质量加权空气动力学粒径分布（APSD），这是吸入式药物产品（OIP）的关键质量属性。这些装置通过增加颗粒速度，逐步对通过一系列包含一个或多个喷嘴的阶段的气溶胶进行尺寸分级。对于给定的多喷嘴阶段，可以通过有效直径（[公式：见文本]）来集体描述喷嘴尺寸，与切割点尺寸相关联，为空气动力学直径提供了联系。用户定期进行级联测量，以确保每个级联的[公式：见文本]都在制造商的公差范围内，但对于应该多久进行一次这样的检查，没有指导。我们研究了这样一种理念，即 OIP 的与颗粒大小相关的规格应确定何时对撞击器进行测量。以通过带有预分离器的下一代撞击器采样的干粉吸入器生成的气溶胶为例，我们发现只有三个关键级联可能对测量的 APSD 产生实质性影响，这是按照当前监管实践分为四组级联的结果。此外，在有最小喷嘴尺寸的最关键级联中，[公式：见文本]可以放宽四倍或更多，才有可能无法测量最细颗粒组中 API 的质量分数，使其达到规定的±10%的名义值以内。因此，我们得出结论，用户应该考虑让 OIP 的 APSD 性能规范根据可接受的级联分组来驱动撞击器质量要求和级联测量的频率。
