The physico-chemical properties of salmeterol and fluticasone propionate in different solvent environments.
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.
Michael
Y
Y
School of Chemical and Life Sciences, University of Greenwich, Wellington Street, Woolwich, SE18 6PF, London, UK.
Chowdhry
B Z
BZ
Ashurst
I C
IC
Snowden
M J
MJ
Davies-Cutting
C
C
Gray
S
S
D000420:Albuterol / Q000031:analogs & derivatives* / Q000737:chemistry; D000730:Androstadienes / Q000737:chemistry*; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane / Q000737:chemistry; D000068298:Fluticasone; D013058:Mass Spectrometry; D000432:Methanol / Q000737:chemistry; D012015:Reference Standards; D000068299:Salmeterol Xinafoate; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D014867:Water / Q000737:chemistry
D000730:Androstadienes; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane; D012997:Solvents; D014867:Water; C007786:1,1,2-trichloro-1,2,2-trifluoroethane; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D000432:Methanol