Determination of Fine Particle Dose for Orally Inhaled Products (OIPs) by Abbreviated Impactor Methodologies: Results from a Multi-Centre Study

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Background: Fine particle dose (FPD) is a critical quality attribute for OIPs. The abbreviated impactor measurement (AIM) concept can simplify its measurement, provided that FPD is comparable with Pharmacopoeial impactor measurement (PIM).  This study compared FPD determined using AIM and PIM for 5 different dry powder inhaler (DPIs) and 2 pressurized metered dose inhaler (pMDI) products, one of which included a valved holding chamber (VHC) add-on device.

Materials and Methods: Reference measurements of FPD were made following pharmacopoeial methods by each of 5 participants using either the full-resolution Andersen 8-stage non-viable impactor (ACI) or Next Generation Impactor (NGI).  FPD was also determined for the same OIP(s) with an abbreviated impactor (fast screening impactor (FSI), fast screening Andersen (FSA) or reduced NGI (rNGI)).  Each organization chose their own validated assay method(s) for the active pharmaceutical compound(s) involved.  Ten replicate measurements were made by both AIM and PIM, with an aim to obtain a 90% confidence interval for the AIM/PIM FPD ratio of length 10% or less. The size limit for FPD varied from 4.4 to 5.0 μm aerodynamic diameter, depending upon flow rate, OIP studied and AIM apparatus; the corresponding FPD size limit for the PIM apparatus was selected to be 5 μm in accordance with the methodology in the European Pharmacopoeia.

Results: The data fulfilled acceptance criteria for 9 of the 10 comparisons of FPD, in that the 90% confidence interval for the FPDAIM/FPDPIM ratio was contained in the predetermined 85 – 118% acceptance interval.  The ratio [FPDAIM/FPDPIM] was on average 104% across all OIPs and apparatuses.

Conclusions:  The findings from this investigation support the equivalence of AIM and PIM for determination of FPD across a wide range of product types, OIP platforms and measurement techniques.

04.Nichols