title: Characterisation of the aggregation behaviour in a salmeterol and fluticasone propionate inhalation aerosol system.
abstract: The nature of the drug-drug aggregation phenomena between salmeterol xinafoate and fluticasone propionate used in a metered-dose inhaler system has been examined. Interactions between the drugs in the solvents 1,1,2-trichlorotrifloroethane (CFC-113) and 1,1,1,2-tetrafluoroethane (HFA-134a) have been characterised using a focused beam reflectance measurement probe by measuring the average floc size of the drug particles individually and in combination as a function of stirrer rate. The floc composition in the CFC-113 system, where the drug particles cream, was determined by high-performance liquid chromatography analysis. The aggregation behaviour of the individual drugs was shown to depend on the physical and chemical properties of both the drug substance and the media. Larger flocs were observed for salmeterol xinafoate compared with fluticasone propionate, while both drugs formed larger aggregates in HFA-134a compared with in CFC-113. The floc composition studies demonstrated that, in the combined formulation in CFC-113, salmeterol xinafoate and fluticasone propionate aggregate together to form hetero-flocs. The interaction between the two drugs was such that they did not separate on creaming, despite having different densities. The average floc size of the combined drug suspension was also found to depend on the dispersion medium.
authors.affiliation: School of Chemical and Life Sciences, University of Greenwich, Wellington Street, Woolwich, London SE18 6PF, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Michael
authors.forename: M J
authors.initials: MJ
authors.lastname: Snowden
authors.forename: B Z
authors.initials: BZ
authors.lastname: Chowdhry
authors.forename: I C
authors.initials: IC
authors.lastname: Ashurst
authors.forename: C J
authors.initials: CJ
authors.lastname: Davies-Cutting
authors.forename: T
authors.initials: T
authors.lastname: Riley
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry*; D000730:Androstadienes / Q000008:administration & dosage / Q000737:chemistry*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane; D004347:Drug Interactions; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated; D000068299:Salmeterol Xinafoate; D005466:Fluorocarbons
chemical_list: D000336:Aerosols; D000420:Albuterol; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated; D000068299:Salmeterol Xinafoate; C007786:1,1,2-trichloro-1,2,2-trifluoroethane; C094049:apaflurane; D005466:Fluorocarbons