The 'stage-by-stage' deposition of drugs from commercial single-active and combination dry powder inhaler formulations

Inhalation of salmeterol xinafoate (SX) and fluticasone propionate (FP) from a combination product is reported to produce superior clinical outcomes in comparison to the concurrent administration of 'similar' doses via separate single-active inhalers. For bioequivalence determination across different products, emphasis is currently placed on the assessment of drug deposition within inertial impactors on a 'stage-by-stage' basis as stipulated in a recent European Medicines Agency guidance. The aim of this study was to compare the stage-by-stage deposition of drugs aerosolised from the single-active Accuhaler (R) products Serevent (R) (SX) and Flixotide (R) (FP) with the SX-FP combination product Seretide (R) Accuhaler (R) in vitro. Drug deposition on a stage-by-stage basis was assessed using the next generation impactor (NGI). Significant differences in drug deposition profiles were obtained following aerosolisation from the single-active versus combination products. The concurrent administration of the two single-active products: Serevent (R) and Flixotide (R) Accuhaler (R) may not be bioequivalent to inhalation of the combination product Seretide (R) Accuhaler (R). The observed differences may have resulted from different characteristics of the active pharmaceutical ingredient (APIs) and the carrier alpha-lactose monohydrate between the single-active and combination inhalers and/or a change in the drug-carrier inter-particulate interaction as a consequence of the presence of a second active. (C) 2011 Elsevier B.V. All rights reserved.