Cascade impactors for the size characterization of aerosols from medical inhalers: their uses and limitations.

Cascade impactors, including the multi-stage liquid impinger, are by far the most widely encountered means for the in vitro determination of the particle size distribution of aerosols from medical inhalers, both in product development, batch release and in applications with add-on devices. This is because they directly measure aerodynamic size, which is the most relevant parameter to describe particle transport within the respiratory tract. At the same time, it is possible to quantify the mass of active pharmaceutical ingredient in different size ranges independent of other non-physiologically active components of the formulation. We begin by providing an overview of the operating principles of impactors and then highlight the various configurations and adaptations that have been adopted to characterize the various classes of inhaler. We continue by examining the limitations of the cascade impaction method, in particular looking at potential sources of measurement bias and discussing both appropriate and inappropriate uses of impactor-generated data. We also present a synopsis of current developments, including the Next Generation Pharmaceutical Impactor, and automation of cascade impactors for routine inhaler performance measurements.