Effect of Interval Between Actuations of Albuterol Hydrofluoroalkane Pressurized Metered-Dose Inhalers on Their Aerosol Characteristics

Abstract

Background: Albuterol hydrofluoroalkane (HFA) either alone or with a valved holding chamber is used to treat bronchoconstriction. Delays between actuation and inhalation are common. Currently, the recommended interval between actuations of an albuterol HFA is 60 s. Using a shorter interval when multiple actuations are ordered will improve productivity in the hospital setting.

Methods: We studied aerosol characteristics of albuterol HFA (Ventolin, ProAir, and Proventil) with a cascade impactor calibrated at 30 L/min. We studied pressurized metered-dose inhalers (pMDI) alone, coupled to a nonelectrostatic valved holding chamber, and coupled to the valved holding chamber but introducing a 10-s delay between actuation and measurement. We tested intervals between actuations of 60, 30, and 15 s (not for delay scenario). The variable of most interest was fine-particle mass. Albuterol was measured by spectrophotometer (276 nm).

Results: Variations in fine-particle mass from 60-s values were < 15% for Ventolin and ProAir for all conditions tested and for Proventil with a valved holding chamber. Variations in fine-particle mass from 60-s values were > 15% for Proventil (pMDI alone with a 30-s interval and pMDI/valved holding chamber with delay and a 30-s interval). Adding a valved holding chamber increased fine-particle mass for all brands (ProAir 7-12%, Ventolin 26-35%, and Proventil 44-47%). The introduction of a 10-s delay reduced fine-particle mass for all brands (ProAir 34-39%, Ventolin 39-42%, and Proventil 27-32%). Comparison of fine-particle mass among brands showed that Proventil was > ProAir > Ventolin.

Conclusions: Decreasing the interval between actuations from 60 to 30 and 15 s does not seem to affect the aerosol characteristics of ProAir and Ventolin. Although some changes were noticed for Proventil, the pMDI outperformed Ventolin that had the lowest fine-particle mass. The use of a valved holding chamber increased fine-particle mass, but introducing a 10-s delay between actuation and inhalation significantly reduced fine-particle mass.

Keywords: aerosol characteristics; delay; drug delivery; metered dose inhaler; particle size; valved holding chamber.