Size distribution measurements of metered dose inhalers using Andersen Mark II cascade impactors.

The performance of Andersen Mark II impactors was investigated theoretically and experimentally. Theoretical calculations were made to assess the impact that differences in jet diameters among Mark II impactors have on size distribution measurements of metered dose inhalers (MDIs). A previous investigation indicated that the jet diameter for stages on Mark II impactors often do not conform to the manufacturer's specifications (Stein and Olson, 1997). For the calculations reported in this paper, only jet diameters that conform to the manufacturer's specifications were considered. The calculations indicate that large differences in the amount of drug collecting on a given stage should be expected among Mark II impactors sampling an identical aerosol-even for Mark II impactors that conform to the manufacturer's specifications. These calculations suggest that it is impractical to analyze size distribution data generated with cascade impactors, such as the Mark II, on a stage-by-stage basis. Experimental measurements of three MDI products were made using three different Andersen Mark II cascade impactors. Measurements of the same product were very consistent for a given impactor, but large differences were observed in measurements of the same product with different impactors. For measurements of QVAR HFA beclomethasone dipropionate MDIs using three Mark II impactors, the amount of drug that collected on Stage 6 ranged from 28.7 to 41.3% of the sampled mass depending on which impactor was used. The theoretical calculations and experimental measurements reported in this paper demonstrate that it is important to consider the limited precision of cascade impactors, such as the Andersen Mark II, when analyzing the size distribution measurements that they provide.