Cascade impaction methods for dry powder inhalers using the high flowrate Marple-Miller Impactor

The magnitude and effects of stage overload and particle re-entrainment in the new, Marple-Miller cascade impactor (MMI) were evaluated at 60 liter/min by sampling and determining the aerodynamic size distributions from two, excipient-free, powder inhalers (Turbohaler(TM) and Spinhaler(TM)) according to a variety of experimental protocols. Drug distributions were compared statistically, for both inhalers, following single dose experiments in the presence and absence of silicone oil impactor stage coating and between single dose and multiple dose experiments in its presence. Stage coating was found to be essential to prevent re-entrainment of drug from both inhalers. One or less than or equal to 25 dose sampling was shown to produce valid results provided impaction stages were coated for the 0.5 mg Bricanyl Turbohaler (44.7 +/- 9.6% of emitted dose < 5 mu m; overload and re-entrainment was evident following sampling of 40 doses). One or 2 dose sampling was shown to produce valid results for 20 mg Spinhaler, provided drug capture was enhanced further by also coating the aerosol inlet port to MMI (10.7 +/- 1.3% of emitted dose < 5 mu m; overload of stage 1 and re-entrainment was evident following sampling of 2 doses in the absence of a coated aerosol inlet port). The absence of significant re-entrainment could be shown most effectively by statistically comparing values for percent deposition, at different sites in the stage-coated impactor, between single and multiple dose (greater than or equal to 2) experiments. Such an experiment should be performed for each type of inhaler and formulation to be tested, as a means of validating the exact impaction technique to be used for size distribution analysis of powder inhaler emissions.