title: The 'stage-by-stage' deposition of drugs from commercial single-active and combination dry powder inhaler formulations.
abstract: 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® products Serevent® (SX) and Flixotide® (FP) with the SX-FP combination product Seretide® Accuhaler® 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® and Flixotide® Accuhaler® may not be bioequivalent to inhalation of the combination product Seretide® Accuhaler®. 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.
authors.affiliation: King's College London, Institute of Pharmaceutical Science, 150 Stamford Street, London SE1 9NH, UK. mohammed.taki@kcl.ac.uk
authors.forename: Mohammed
authors.initials: M
authors.lastname: Taki
authors.forename: Sarah
authors.initials: S
authors.lastname: Ahmed
authors.forename: Christopher
authors.initials: C
authors.lastname: Marriott
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Zeng
authors.forename: Gary P
authors.initials: GP
authors.lastname: Martin
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000730:Androstadienes / Q000008:administration & dosage* / Q000737:chemistry; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004338:Drug Combinations; D058995:Dry Powder Inhalers / Q000295:instrumentation / Q000379:methods*; D000068298:Fluticasone; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D000068299:Salmeterol Xinafoate
chemical_list: D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol