The relative influence of atomization and evaporation on metered dose inhaler drug delivery efficiency

Factors influencing the delivery efficiency from HFA-134a MDIs were examined theoretically and experimentally. The time required for evaporation of HFA-134a and ethanol droplets were theoretically calculated. HFA-134a droplets were shown to evaporate approximately seven times faster than ethanol droplets of the same size, even though HFA-134a droplets cool to approximately 78 degrees below ambient temperature during evaporation. MDI delivery efficiency was experimentally shown to decrease with increasing ethanol concentration, however, the corresponding decrease in vapor pressure was not the primary variable responsible for the decreased efficiency. Rather, this was shown to be primarily due to the increased time required for the droplets to evaporate as ethanol concentration increased. Droplets that evaporate slowly remain for a longer period in the size range that is more likely to deposit via turbulent deposition in the actuator mouthpiece or USP Inlet during cascade impaction tests. Tests with experimental MDIs using alternative cosolvents confirmed that MDI delivery efficiency is much more sensitive to the time required for evaporation of the droplets than on the formulation vapor pressure or the size of the atomized droplets. This indicates that factors affecting the evaporation of an MDI aerosol play a larger role in determining MDI delivery efficiency than do atomization effects.