Particle Size Measurements from Orally Inhaled and Nasal Drug Products.

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.