fluticasone and 1-1-2-trichloro-1-2-2-trifluoroethane

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.

Topics: Administration, Inhalation; Aerosols; Albuterol; Androstadienes; Anti-Asthmatic Agents; Chemistry, Pharmaceutical; Chlorofluorocarbons, Ethane; Chlorofluorocarbons, Methane; Drug Interactions; Fluticasone; Hydrocarbons, Fluorinated; Salmeterol Xinafoate

The physico-chemical properties of two anti-asthmatic drugs, salmeterol xinafoate and fluticasone propionate, have been studied in both aqueous and non-aqueous solvent environments. Ultraviolet-visible (UV-Vis) spectroscopy, fluorescence spectroscopy and electrospray ionisation mass spectrometry (ESI-MS) have been used to characterise the interaction of the drugs in 70:30 (v/v) methanol/water solutions. First derivative UV-Vis spectra measurements indicate that an interaction takes place between the two drugs in a binary solvent system. Fluorescence studies indicate that an increase in the concentration of fluticasone propionate results in a decrease in the fluorescence signal of the salmeterol for mixed solutions of the drugs. Analysis of a mixture of the two drug solutions using mass spectrometry also shows evidence of salmeterol-fluticasone propionate interaction and dimer formation with respect to both the salmeterol and the fluticasone propionate. Model metered dose inhalers (MDI) of both individual samples and mixtures of the drugs were formulated as suspensions in solvent CFC-113. The extent of deposition onto different inhaler components, such as the aluminium alloy canister, Teflon coated canister and the metering valve was evaluated by high-performance liquid chromatography (HPLC) of the methanol/water washings of the deposited drug(s). Changing the nature of the surface properties of the container resulted in a significant difference in the extent of deposition. The deposition of the individual drugs was found to increase as the dispersion concentration of the drug increases. However, the formulation based on a combination of the two drugs was found to show different deposition behaviour compared to the individual drug formulations. The deposition of the drugs, onto the aluminium alloy canister and the metering valve, decreases as the combined dispersion concentration of the two drug increases.

Topics: Albuterol; Androstadienes; Chlorofluorocarbons, Ethane; Chlorofluorocarbons, Methane; Fluticasone; Mass Spectrometry; Methanol; Reference Standards; Salmeterol Xinafoate; Solvents; Spectrophotometry, Ultraviolet; Water