SURFACTANT-MEDIATED EFFECTS IN PRESSURIZED METERED-DOSE INHALERS FORMULATED AS SUSPENSIONS .1. DRUG SURFACTANT INTERACTIONS IN A MODEL PROPELLANT SYSTEM
Jg. Clarke et al., SURFACTANT-MEDIATED EFFECTS IN PRESSURIZED METERED-DOSE INHALERS FORMULATED AS SUSPENSIONS .1. DRUG SURFACTANT INTERACTIONS IN A MODEL PROPELLANT SYSTEM, International journal of pharmaceutics, 93(1-3), 1993, pp. 221-231
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.