THE USE OF LOW-FREQUENCY DIELECTRIC ANALYSIS IN THE CHARACTERIZATION OF METERED-DOSE INHALER FORMULATIONS

The use of low frequency dielectric spectroscopy as a novel means of studying metered dose inhaler preparations is described using a simple model system comprising a propellant (Propellant 113, 1,1,2-trichlorotrifluoroethane), a drug (salbutamol sulphate) and a surfactant (sorbitan trioleate). The dielectric spectrum of Propellant 113 was obtained over a frequency range of 10(-2)-10(4)Hz and was shown to exhibit a small increase in capacitance but no discernible increase in conductivity compared to the empty cell. Addition of 1% w/w salbutamol sulphate did not result in a significant change in response. Measurement of the response of sorbitan trioleate (0.05-5% w/w) in Propellant 113 showed a concentration dependent increase in conductivity. However, this conductivity was shown to decrease in the presence of 1% w/w drug, implying that the surfactant was adsorbed onto the surface of the drug. Furthermore, the decrease was most marked for lower surfactant concentrations, with an inflexion in the conductivity/concentration curve being observed between approx. 0.5 and 1% w/w surfactant. This correlates with particle size analysis data which showed evidence for aggregation of drug particles at surfactant concentrations up to approximately 0.3%-0.5% w/w. Therefore, the study implies that dielectric analysis may be used as a means of monitoring the adsorption of surfactant onto the surface of drug particles in metered dose inhaler formulations, thereby representing a novel means of characterising these systems in situ.