A Laboratory Investigation of Medication Delivery by Pressurized Metered Dose Inhaler with Valved holding chamber Using a Model Adult Oropharyngeal Airway and Inhalation Flow Profiles from Trained Healthy Adults

Patient inhalation flow-elapsed time profiles using pressurized metered dose inhalers (pMDIs) can be highly variable for several reasons, including inability to maintain a consistent flow rate-time profile. We report a laboratory-based study measuring how inhalation profiles from trained adults may affect inhaled potential lung-delivered mass of a widely prescribed short-acting bronchodilator via a pMDI-valved holding chamber (spacer) combination. Adult inhalation profiles from a previous study inhaling room air without medication were obtained after (a) taking a long slow inhalation followed by a 5-s breath hold (method A); (b) inhaling tidally for 2-3 respiration cycles (method B). Each profile was replayed in a simulation where albuterol (100 μg/actuation) was ‘inhaled’ in vitro via an adult oropharyngeal model connected to a filter distal to the model, with flow controlled via breathing simulator. Filter-collected albuterol provided total mass/actuation available for lung delivery (3-replicates/individual/inhalation profile). Total inhaled volume varied widely and ranges between sexes differed (M: 155-5002 ml, F:214-2711 ml – deep inhalation; M: 617-7722 ml, F:450-3789 ml – tidal breathing). Large variability was observed in potential lung-deliverable drug mass (RSD = 30.1% method A; 30.3% method B) across all inhalation profiles for either method. Intra-profile variability was no worse with either breathing maneuver. Large inter-subject variability in inhalation profiles also existed with either method A or method B. The primary function of the valved holding chamber to retain medication until inhaled was met, since some albuterol was delivered to the filter distal to the oropharyngeal model even in the worst cases.