Aqueous dispersions in pressurized metered-dose inhalers (pMDI) are candidate formulations for the delivery of polar drugs, including biomolecules, to and through the lungs. pMDIs are the mostly widely used and least expensive aerosol delivery vehicles available in the market. However, the replacement of CFCs with the more environmentally friendly hydrofluoroalkane (HFA) propellants (HFA134a and HFA227) has led to an extensive reformulation of pMDIs. The biggest hurdle in reformulating HFA-based pMDIs comes from the fact that CFCs and HFAs have significantly different solvent properties. For example, the surfactants in FDA-approved pMDIs have negligible solubility in HFAs. Moreover, the lack of fundamental knowledge about the interfacial properties of the bare and surfactant modified HFA-water (HFA|W) interface is also preventing us from extending the applicability of pMDIs to the delivery of polar molecules that can be used to treat medically important diseases including cancer, cystic fibrosis and diabetes.

We have developed a series of biodegradable and biocompatible nonionic amphiphiles that are highly active at the HFA|W interface. These surfactants are shown to aggregate in the semi-fluorinated alkanes in the presence of water, and tend to self emulsify as very low tensions are achieved. With addition of cosolvents, the amphiphiles are also shown to form stable water-in-HFA (W/HFA) microemulsions. The microstructure of the aggregates and their ability to uptake biomolecules was characterized in situ. Stable W/HFA emulsions containing biomolecules can be also formed. The in vitro characteristics of the corresponding aerosols were established using Anderson Cascade Impaction. The bioactivity of a model biomolecule in the aqueous dispersions in HFA was also determined.