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 a cid) with various microparticulate systems dispersed in a model chloro fluorocarbon, trichlorotrifluoroethane (P113), has been examined. Olei c 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 de monstrate that oleic acid adsorbed onto salbutamol via an acid-base re action resulting in a breakdown of crystal structure at surfactant/dru g weight ratios > 0.6. The same surfactant demonstrated relatively poo r adsorption onto micronized particulate dispersions of the sulphate a nd bitartrate salts of isoprenaline. Sorbitan trioleate showed physiso rption onto all drug particles; adsorption and multilayer formation we re favoured at higher surfactant concentrations and with more hydrophi lic surfaces (isoprenaline sulphate > isoprenaline bitartrate > salbut amol). 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 surfa ce 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.