Reverse aqueous emulsions and microemulsions in HFA227 propellant stabilized by non-ionic ethoxylated amphiphiles

In this work we use in situ high-pressure tensiometry to screen non-ionic ethoxylated surfactants at the 1,1,1,2,3,3,3-heptafluoropropane (HFA227) propellant|Water (HFA227|W) interface. The EOnPO∼30EOn series, where EO stands for ethylene oxide and PO for propylene oxide, and n the number of repeat EO units, was selected for this study based on the favorable interactions reported between HFA propellants and the PO moiety. The surfactants used in FDA-approved pressurized metered-dose inhaler formulations were also investigated. Tension measurements provide not only information on the relative activity of the different surfactants in the series, but they also serve as a guide for selecting an appropriate candidate for the formation of reverse aggregates based on the surfactant natural curvature. Moreover, the effect of ethanol and the chemistry of the surfactant tail group on the surfactant activity were also investigated. Surfactants with hydrogenated tails are not capable of forming stable water-in-HFA227 microemulsions. This is true even at very low tensions observed when in the presence of ethanol, indicating the lack of affinity between HFA227 and hydrogenated moieties—the surfactant does not tend to curve about water. On the other hand, PO-based amphiphiles can significantly reduce the tension of the HFA227|W interface. Small angle neutron scattering (SANS) and UV–vis spectroscopy results also reveal that a selected ethoxylated amphiphile (EO13PO30EO13 at 1 mM concentration), when in the presence of ethanol, is capable of forming stable cylindrical reverse aqueous microemulsions. EO13PO30EO13 is also capable of forming emulsions of water-in-HFA227 that are fairly stable against coalescence. Such dispersions are potential candidates for the delivery of small polar solutes and larger therapeutic biomolecules to and through the lungs in the form of pMDI formulations, and in other medical sprays.