Combining a positive expiratory pressure device with a metered-dose inhaler reservoir system using chlorofluorocarbon albuterol and hydrofluoroalkane albuterol: effect on dose and particle size distributions

Abstract

Background: Combining a positive expiratory pressure (PEP) device with inhalation of albuterol via metered dose inhaler (MDI) may improve drug delivery to the lung, but may also affect dose availability.

Purpose: Determine the effect of interposing a PEP device on dose availability of albuterol via MDI and reservoir with either a chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA) propellant.

Methods: MDI dose availability of CFC albuterol (Proventil) and HFA albuterol (Proventil HFA) using an Aerosol Cloud Enhancer (ACE) reservoir with and without a PEP device (TheraPEP) attached was determined. Drug availability was assessed using an Andersen 8-stage cascade impactor operated at 28.3 +/- 0.5 L/min. The PEP device was inserted between the reverse-firing ACE and the United States Pharmacopeia induction throat. Drug collected on impactor plates was analyzed spectrophotometrically at 276 nm, and the fine particle fraction was determined as the mass of drug < 4.7 microns.

Results: With CFC albuterol, total dose and drug mass < 4.7 microns (means and standard deviations) for the MDI-ACE alone were 44.4 +/- 7.7 micrograms and 33.4 +/- 2.2 micrograms, respectively, and for the MDI-ACE with TheraPEP were 50.1 +/- 6.4 micrograms and 39.8 +/- 14.3 micrograms, respectively. With HFA-albuterol sulfate, total drug and drug mass < 4.7 microns for the MDI-ACE alone, expressed as base drug, were 41.7 +/- 4.2 micrograms and 35.2 +/- 6.3 micrograms, respectively, and for the MDI-ACE with TheraPEP were 48.9 +/- 8.0 micrograms and 44.2 +/- 6.2 micrograms, respectively. There was no significant difference in dose availability between the MDI-ACE alone and with the PEP device attached (Wilcoxon signed-rank test, p > 0.05), for either CFC or HFA albuterol.

Conclusion: Interposing the TheraPEP device at the MDI-ACE outlet does not change total dose, drug mass < 4.7 microns, or mass median aerodynamic diameter of MDI albuterol, with either CFC or HFA propellants.