Characterisation of the aggregation behaviour in a salmeterol and fluticasone propionate inhalation aerosol system

The nature of the drug-drug aggregation phenomena between salmeterol xinafo ate and fluticasone propionate used in a metered-dose inhaler system has be en examined. Interactions between the drugs in the solvents 1,1,2-trichloro trifloroethane (CFC-113) and 1,1,1,2-tetrafluoroethane (HFA-134a) have been characterised using a focused beam reflectance measurement probe by measur ing the average flee size of the drug particles individually and in combina tion as a function of stirrer rate. The flee composition in the CFC-113 sys tem, where the drug particles cream, was determined by high-performance liq uid chromatography analysis. The aggregation behaviour of the individual dr ugs was shown to depend on the physical and chemical properties of both the drug substance and the media. Larger flocs were observed for salmeterol xi nafoate compared with fluticasone propionate, while both drugs formed large r aggregates in HFA-134a compared with in CFC-113. The flee composition stu dies demonstrated that, in the combined formulation in CFC-113, salmeterol xinafoate and fluticasone propionate aggregate together to form hetero-floc s. The interaction between the two drugs was such that they did not separat e on creaming, despite having different densities. The average flee size of the combined drug suspension was also found to depend on the dispersion me dium. (C) 2001 Elsevier Science B.V. All rights reserved.