Cascade Impactor Practice for a High Dose Dry Powder Inhaler at 90 L/min: NGI Versus Modified 6-Stage and 8-Stage ACI

Abstract The compendial methods of particle size distribution (PSD) profile determination for dry powder inhalers (DPIs) were compared between the Next Generation Pharmaceutical Impactor (NGI) and the Andersen Cascade Impactor (ACI). Relenza® Rotadisk® (zanamivir) and Diskhaler® was used as a model DPI and sampled into each impactor via its preseparator (PS), at 90 L/min under various protocols. In the NGI, silicone coating was shown to be indispensable to prevent or minimize particle bounce and reentrainment, and to reduce wall losses to the levels acceptable to the compendia (5%). In contrast, the ACI exceeded this 5% limit, regardless of coating, implying different wall loss mechanisms from the NGI. Particle bounce occurred in both impactors, inaccurately undersizing the PSD profiles for Relenza®, unless the collection surfaces were coated or an increased number of doses were employed. Hence, the PSD profile for Relenza® following single dose collection in the stage-coated NGI was the most accurate. In contrast, the use of the ACI and its PS for Relenza® at 90 L/min suffered from several problems, even though the poorly designed PS still resulted in consistent impactor dose and PSD profiles, compared to those obtained from the NGI and its PS.