Loading Effect on Particle Size Measurements by Inertial Sampling of Albuterol Metered Dose Inhalers

Purpose. The purpose of this study is to investigate the albuterol loading effect on particle size measurements by studying the effect of the amount of albuterol delivered, the number of puffs used, and the sampling techniques used in particle size measurement. Methods. Particle size distribution profiles for different albuterol loadings were evaluated using an 8-stage cascade impactor and a sensitive HPLC electrochemical assay method. A commercial albuterol MDI (Proventil^R) and other specially prepared albuterol MDIs were used in the study. Results. As the amount of albuterol was increased, either by increasing the number of puffs or the amount delivered per puff, the measured MMAD increased. This increase was more prominent in some formulations (Proventil^R) than others. Further, albuterol particles previously deposited on the valve and/or actuator didn't play a role in the observed multi-puff/loading effect. Conclusions. The collection of the least amount of aerosol in a cascade impactor provides a better estimate of MMAD, as it minimizes modifications of the collection surfaces.