title: Co-deposition of salmeterol and fluticasone propionate by a combination inhaler.
abstract: The combination of the long-acting beta2-agonist, salmeterol xinafoate (salmeterol) and inhaled corticosteroid, fluticasone propionate (FP) (Seretide/Advair) has shown enhanced efficacy compared with concurrent administration of the two drugs from individual inhalers at the same dose. A possible explanation for this increased effect is a higher degree of co-deposition of the two drugs from the combination (Seretide) inhaler compared with the component drugs administered separately. Raman laser spectroscopy, a technique capable of identifying individual drug particles, has been used with novel statistical methodology that we have developed, to determine whether there is any co-association between drug particles and whether this occurs in the Seretide formulation rather than by chance. Samples from a combined Seretide metered dose inhaler (MDI, 25/50 mcg) and salmeterol (25 mcg) with FP (50 mcg) from separate MDI's taken from Plate 4 of an Anderson Cascade Impactor were analysed. Using a statistical test based on the bootstrap technique, it was found that the co-deposition of FP and salmeterol particles from the combination MDI was significantly greater than from the separate inhalers group (p < 0.001). A higher degree of co-deposition on the same cells of the airways may possibly account for the increased efficacy observed in patients prescribed Seretide MDI.
authors.affiliation: Department of World-wide Physical Properties, GSK R&D, Ware, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Theophilus
authors.forename: Alison
authors.initials: A
authors.lastname: Moore
authors.forename: Dave
authors.initials: D
authors.lastname: Prime
authors.forename: Simona
authors.initials: S
authors.lastname: Rossomanno
authors.forename: Brandon
authors.initials: B
authors.lastname: Whitcher
authors.forename: Henry
authors.initials: H
authors.lastname: Chrystyn
mesh_terms: D000318:Adrenergic beta-Agonists / Q000737:chemistry*; D000336:Aerosols; D000420:Albuterol / Q000031:analogs & derivatives* / Q000737:chemistry; D000730:Androstadienes / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D003627:Data Interpretation, Statistical; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D036501:Metered Dose Inhalers; D013059:Spectrum Analysis, Raman / Q000379:methods
chemical_list: D000318:Adrenergic beta-Agonists; D000336:Aerosols; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000420:Albuterol