The effect of a holding chamber on albuterol metered-dose inhaler product differences

Background Three albuterol sulfate metered-dose inhaled (MDI) products (Ventolin HFA, Proventil HFA, and ProAir HFA) are marketed in the United States to provide the same total dose of albuterol sulfate. However, it is widely known that the fine particle dose (<5 μm) is the portion of the particle distribution that actually reaches the lungs and provides therapeutic benefit. Objective To examine the differences in particle size between products and how a valved holding chamber (VHC) can mitigate possible adverse effects. Methods Particle size distributions in each product were measured, with and without a VHC, and were analyzed by high-performance liquid chromatography. Results The only significant mean (SD) difference in total dose was between Proventil (75 [21] μg) and ProAir (107 [12] μg) (P <. 01). The fine particle doses of all 3 products were significantly different: 21 (5) μg of albuterol sulfate for Ventolin, 40 (4) μg of albuterol sulfate for Proventil, and 64 (7) μg of albuterol sulfate for ProAir (P <. 001 for all 3 cases). The VHC successfully removed the larger particle dose delivered by all 3 products (P ≤. 01) without reducing the fine particle dose (P >. 05). Conclusion Ventolin, Proventil, and ProAir should not be considered interchangeable products. In this study, the dose of albuterol sulfate likely to reach the lungs with Proventil or ProAir is 2 to 3 times that of Ventolin. As such, patients with asthma may require 3 additional puffs of Ventolin to achieve a clinical benefit similar to Proventil or ProAir. Because all 3 products contain 200 actuations, it also follows that Proventil or ProAir products may last a user 2 to 3 times longer than Ventolin.