Determination of nebulizer droplet size distribution: a method based on impactor refrigeration.

Size distributions of droplets generated by nebulizers are difficult to determine because of evaporation after aerosolization. We describe a method whereby a Next Generation Pharmaceutical Impactor (NGI; MSP Corporation, Shoreview, MN) is refrigerated at 5 degrees C before connecting it to the nebulizer in order to ensure an environment inside the NGI at close to 100% relative humidity (RH). This, in turn, reduces droplet evaporation between the nebulizer and impaction. The method development was performed with a Pari LC Plus jet nebulizer operated at 2.0 bar, with the NGI set at a flow rate of 15 L/min and with salbutamol 5.0 mg/mL as the test solution. The droplet size distributions were expressed in terms of mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD). Variation in test conditions showed that the NGI should be cooled for at least 90 min, that nebulization should be started within 5 min after removal from the refrigerator, and that coating of collecting cups to prevent "bouncing" is not necessary. Variation of ambient temperature and humidity had no relevant effect on results. MMAD and GSD results showed that refrigeration of the NGI resulted in droplet size distributions that are likely to reflect those originally delivered at the mouthpiece by the nebulizer. The method was shown to be robust, accurate with recovery of test solutions exceeding 99%, reproducible, and to be suitable for use with a wide range of commercially available nebulizers.