SURFACTANT-MEDIATED EFFECTS IN PRESSURIZED METERED-DOSE INHALERS FORMULATED AS SUSPENSIONS .1. DRUG SURFACTANT INTERACTIONS IN A MODEL PROPELLANT SYSTEM

The surface interaction of surfactants (sorbitan trioleate and oleic acid) with various microparticulate systems dispersed in a model chlorofluorocarbon, trichlorotrifluoroethane (P113), has been examined. Oleic acid showed Langmuirian adsorption onto alpha-alumina, the extent of adsorption inversely proportional to the equilibrium moisture content of the adsorbent. ATR spectroscopy coupled to FTIR was employed to demonstrate that oleic acid adsorbed onto salbutamol via an acid-base reaction resulting in a breakdown of crystal structure at surfactant/drug weight ratios > 0.6. The same surfactant demonstrated relatively poor adsorption onto micronized particulate dispersions of the sulphate and bitartrate salts of isoprenaline. Sorbitan trioleate showed physisorption onto all drug particles; adsorption and multilayer formation were favoured at higher surfactant concentrations and with more hydrophilic surfaces (isoprenaline sulphate > isoprenaline bitartrate > salbutamol). The electrophoretic mobility of salbutamol in P113, determined by laser Doppler velocimetry, became more negative on increasing oleic acid concentration but remained largely unchanged in the presence of sorbitan trioleate. However, in all cases, calculated values for surface zeta potential were very low. The collective data are discussed in relation to the likely mechanism of stabilization of drug dispersions within metered dose inhalers formulated as suspensions.