The Effect of Nonideal Cascade Impactor Stage Collection Efficiency Curves on the Interpretation of the Size of Inhaler-
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Research Article The Effect of Nonideal Cascade Impactor Stage Collection Efficiency Curves on the Interpretation of the Size of Inhaler-Generated Aerosols D. L. Roberts1 and J. P. Mitchell2,3
Received 9 October 2012; accepted 29 January 2013 Abstract. Cascade impactors, operating on the principle of inertial size separation in (ideally) laminar flow, are used to determine aerodynamic particle size distributions (APSDs) of orally inhaled product (OIP) aerosols because aerodynamic diameter can be related to respiratory tract deposition. Each stage is assumed typically to be an ideal size fractionator. Thus, all particles larger than a certain size are considered collected and all finer particles are treated as penetrating to the next stage (a step function stage efficiency curve). In reality, the collection efficiency of a stage smoothly increases with particle size as an “S-shaped” curve, from approximately 0% to 100%. Consequently, in some cases substantial overlap occurs between neighboring stages. The potential for bias associated with the step-function assumption has been explored, taking full resolution and two-stage abbreviated forms of the Andersen eight-stage nonviable impactor (ACI) and the next-generation pharmaceutical impactor (NGI) as example apparatuses. The behavior of unimodal, log-normal APSDs typical of OIP-generated aerosols has been investigated, comparing known input values to calculated values of central tendency (mass median aerodynamic diameter) and spread (geometric standard deviation, GSD). These calculations show that the error introduced by the step change assumption is larger for the ACI than for the NGI. However, the error is sufficiently small to be inconsequential unless the APSD in nearly monodisperse (GSD ≤1.2), a condition that is unlikely to occur with realistic OIPs. Account may need to be taken of this source of bias only for the most accurate work with abbreviated ACI systems. KEY WORDS: cascade impactor; inhaler aerosol; inhaler testing; size distribution.
INTRODUCTION Cascade impactors (CIs) operate on the principle of inertial size-separation in laminar flow (1). They are widely used to determine aerodynamic particle size distributions (APSDs) of orally inhaled product (OIP) aerosols because aerodynamic size can be related to particle deposition in the respiratory tract (2). Furthermore, the mass of active pharmaceutical ingredient (API) can be recovered from a CI and assayed quantitatively in a fully traceable manner (3). The European and US pharmacopeial methods for APSD assessment (4,5) describe specific CIs including the widely used Andersen eight-stage nonviable impactor (ACI) and the next-generation pharmaceutical impactor (NGI). Regulatory agency guidance documents relating to the in vitro testing of OIPs cite the use of cascade impaction as the norm for the aerodynamic particle size assessment of emitted aerosols (6–8). Electronic supplementary material The online version of this article (doi:10.1208/s12249-013-9936-2) contains supplementary material, which is ava
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