Cascade impaction and laser diffraction measurements of inhalation aerosols: A refined data analysis guidance

Cascade impactors are the gold standard for the measurement of the aerodynamic particle size distribution of orally inhaled aerosols. They are essential tools in the development and the quality control of inhalation aerosols. Nevertheless, they should not be assumed to simulate particle deposition in the respiratory tract. Critical review of cascade impaction measurements reported in the pharmaceutical literature raises concerns regarding conventional approaches used for analysis and presentation of the measurements. Calls to revisit these approaches have been raised, but the recommendations remain far from broad implementation. Laser diffraction is also used for studying the particle size distribution of inhalation aerosols. Conventional approaches used for analysis of laser diffraction measurements of inhalation aerosols do not fully exploit the potential of the measurements. This article provides comprehensive guidance on analysis of cascade impaction and laser diffraction measurements of inhalation aerosols. The theoretical basis of the particle size distribution data measured by each technique is first outlined. For illustration, a carrier-free and a series of carrier-based model dry powder inhalation formulations were studied by cascade impaction and laser diffraction. The measurements were thoroughly analyzed and presented. The analysis exploited the potential of each measurement and drew attention to potential sources of misinterpretation and bias.