Effects of Shake-Actuation Delay on Delivered Dose and Aerosol Characteristics of an Albuterol Suspension From a Pressurized Metered-Dose Inhaler.

ABSTRACT

BACKGROUND: Suspensions delivered via a pressurized metered-dose inhaler (pMDI) require shaking the canister before actuation to prevent drug sedimentation. We hypothesized that a shake-actuation delay of an albuterol hydrofluoroalkane (HFA) pMDI will increase and decrease delivered dose (DOSE) at the beginning and end of the canister's life, respectively, and that aerosol characteristics will remain unchanged with the delay. METHODS: Albuterol HFA pMDIs (90 µg/actuation, 200 doses) operated with and without a 30-s shake-actuation delay, and with and without a valved holding chamber (VHC), were studied. Ten puffs, with a 30-s interval between puffs and 5s of shaking, were actuated into a drug-recovery apparatus. Inhalers were studied throughout their entire life (from 200 doses to 0 remaining doses). Particle size analysis was performed with cascade impaction at the beginning, middle, and end of the canister's life. Albuterol mass was determined via spectrophotometry (276 nm). RESULTS: Mean (99% CI) delivered dose without shake-actuation delay was 100.4% (98.1-102.9%) of the nominal dose. Mean (99% CI) delivered dose with a VHC without a shake-actuation delay was 48.6% (46.2-50.9%) of the nominal dose. The shake-actuation delay increased and decreased delivered dose at the beginning and end of the canister's life, respectively, irrespective of VHC use. Decline in delivered dose began when 110-120 doses remained in the canister. Aerosol characteristics remained constant throughout the canister's life except for the amount of drug captured by the impactor for the pMDI with delay and the pMDI/VHC with delay. Adding a VHC to a pMDI operated with a delay increased fine-particle fraction and decreased the amount of drug captured by the impactor at the middle and at the end of the canister's life. CONCLUSIONS: A 30-s shake-actuation delay of an albuterol HFA pMDI increased and decreased delivered dose at the beginning and end of canister's life, respectively. Particle size characteristics at the end of the canister's life changed when the pMDI and pMDI/VHC were operated with a shake-actuation delay. Patients should re-shake the pMDI if it is not actuated immediately after shaking the canister.