Water soluble compounds have been incorporated into solution phase metered dose inhalers (MDIs) utilizing lecithin inverse microemulsions in dimethyl ether (DME) and propane. DME and propane acted as both solvent and propellant. Experiments utilizing model propellants (dimethylethyleneglycol (DMEG) and hexane) were used to investigate microemulsion physicochemical phenomena, and the results were used to design and interpret the technically more challenging MDI experiments. NMR and viscosity experiments with model propellants were consistent with a 'sphere-to-string' micellar shape change as the solvent was varied from pure DMEG to pure hexane. Water soluble solutes, including selected peptides and fluorescently labeled poly-alpha,beta-[N-(2-hydroxyethyl) D,L-aspartamide] (fPHEAs), dissolved in DME/propane dependent on lecithin and water content. MDIs containing microemulsions generated aerosols with mass median aerodynamic values ranging from 2.7 to 3.1 mum, within the range of commercially available formulations. Fine particle fraction values (50-70%) exceeded those of commercial formulations. fPHEA up to l8 kDa did not adversely affect the aerosol characteristics. Deposition of the aerosol onto a water surface resulted in the formation of liposomes with partially entrapped solute
