Investigating the Evaporation of Metered-Dose Inhaler Formulations in Humid Air: Single Droplet Experiments

Abstract

The effect of excipients and humidity on the evaporation of propellant from metered-dose inhaler (MDI) formulations was examined by means of single, pendant droplet experiments. Droplets of pure hydrofluoroalkane (HFA) 227ea propellant, as well as propellant-ethanol and propellant-ethanol-sorbitan-trioleate mixtures, were suspended by needle into a conditioned viewing chamber. Droplet evaporation was recorded through a microscope-coupled CCD camera for each mixture, with viewing chamber conditions of 37 degrees C and either 100% or <10% relative humidity, over a size range from approximately 4 to approximately 1 microL. Volume versus time data was collected for each droplet through digital processing of image frames, according to Axisymmetric Drop Shape Analysis (ADSA) routines. No significant difference was observed in the rate of change of droplet volume (i.e., evaporation rate) between dry and humid conditions, regardless of the formulation studied. In addition, the rate of propellant evaporation appeared unchanged despite the addition of 15% w/w ethanol to HFA 227ea, while only slight reductions in evaporation rate were observed for a mixture containing 15% ethanol and 0.2% sorbitan trioleate. It was concluded that the rate of evaporation of propellant from HFA-based MDI formulations likely remains unchanged in the presence of high levels of humidity. Therefore, alternative explanations should be explored to explain the increase in MDI particle deposition in highly humid, confined airways.