Aerodynamic deposition of combination dry powder inhaler formulations in vitro: a comparison of three impactors.

Inertial impaction is generally regarded as the 'gold standard' for the in vitro assessment of aerodynamic deposition of inhaled formulations. Despite the availability of several impactors, few studies have compared measurements of aerodynamic deposition using multiple impactors and none employed a combination formulation. The aerodynamic deposition of the combination dry powder inhaler (DPI) Seretide Accuhaler, which contains salmeterol xinafoate (SX) and fluticasone propionate (FP), was assessed using the Andersen cascade impactor (ACI), multi-stage liquid impinger (MSLI) and next generation impactor (NGI) and the results were compared. Two Seretide products were tested at flow rates of 30 and QLmin(-1), the latter corresponding to a pressure drop of 4kPa across the device. Significant differences in the particle size distributions were observed when the same formulation was tested using various impactors. The ACI was found to be less suitable for DPI testing at flow rates considerably higher than 28.3Lmin(-1) due to the significant overlap in the cut-off curves of the pre-separator and stage 0. This was not the case with the MSLI but the data derived were limited by the relatively small number of stages. Deposition data determined by the three impactors were significantly different. The NGI produced good resolution and minimal inter-stage overlap and was regarded as the impactor of choice for DPI testing.