Mitchell Jolyon P
Jolyon Mitchell Inhaler Consulting Services, London, Ontario, Canada.
J Aerosol Med Pulm Drug Deliv. 2021 Dec;34(6):325-345. doi: 10.1089/jamp.2021.29047.jpm.
Particle size measurement of aerosolized particles from orally inhaled and nasal drug products (OINDPs) can be used to assess the likely deposition distribution in the human respiratory tract (HRT). Size is normally expressed in terms of aerodynamic diameter, since this scale directly relates to the mechanics of particle transport from inhaler to deposition locations. The multistage cascade impactor (CI) is the principal apparatus used to size fractionate aerosols in terms of their aerodynamic particle size distributions (APSDs). Clinically meaningful metrics, such as fine and coarse particle mass fractions, can be determined from the cumulative mass-weighted APSD. In effective data analysis (EDA), CI data are reduced to small and large particle mass. The sum and ratio of these metrics are used to characterize impactor-sized mass, without the need for stage groupings or other APSD interpretation. Aerosol characterization by full-resolution CI is complex, and so, an abbreviated impactor measurement has recently come to prominence. Here, multiple stages of the CI are reduced to just one or two size fractionating stages so that measures of fine (and extrafine) particle mass from a two-stage system can be directly determined without the need to group the mass of active pharmaceutical ingredient (API) on adjacent stages. Time-of-flight-based methods determine APSD more rapidly but require refinements such as single-particle mass spectroscopy to relate size measurements to API content. Alternatives for size characterizing OINDP aerosols are few; laser diffractometry is by far the most important, especially for nasal sprays and solution-based orally inhaled formulations in which there is no confounding of data from suspended excipient(s). Laser-phase Doppler anemometry (L-PDA) has also been shown to be useful for nasal sprays. If aerodynamic size-related information is not a priority, optical microscopy combined with Raman chemical imaging offers prospects for separate determination of API components in combination product-generated aerosols.
口服吸入和鼻腔给药产品（OINDPs）雾化颗粒的粒径测量可用于评估其在人体呼吸道（HRT）中的可能沉积分布。粒径通常以空气动力学直径表示，因为该尺度直接关系到颗粒从吸入器到沉积位置的传输机制。多级串联撞击器（CI）是根据气溶胶的空气动力学粒径分布（APSDs）对气溶胶进行粒径分级的主要仪器。可以从累积质量加权APSD中确定具有临床意义的指标，如细颗粒和粗颗粒质量分数。在有效的数据分析（EDA）中，CI数据被简化为小颗粒和大颗粒质量。这些指标的总和与比值用于表征撞击器分级的质量，而无需进行阶段分组或其他APSD解释。通过全分辨率CI进行气溶胶表征很复杂，因此，一种简化的撞击器测量方法最近受到了关注。在这里，CI的多个阶段被简化为仅一两个粒径分级阶段，这样就可以直接确定两阶段系统中细颗粒（和超细颗粒）质量的测量值，而无需将活性药物成分（API）的质量分组到相邻阶段。基于飞行时间的方法能更快地确定APSD，但需要诸如单颗粒质谱等改进措施，以便将粒径测量与API含量相关联。用于表征OINDP气溶胶粒径的替代方法很少；激光衍射法是迄今为止最重要的方法，特别是对于鼻腔喷雾剂和基于溶液的口服吸入制剂，其中悬浮辅料的数据不会产生混淆。激光相位多普勒风速仪（L-PDA）也已被证明对鼻腔喷雾剂有用。如果与空气动力学尺寸相关的信息不是优先考虑的因素，那么光学显微镜结合拉曼化学成像为单独测定组合产品产生的气溶胶中的API成分提供了前景。
