Comparative in vivo lung delivery of hydrofluoroalkane-salbutamol formulation via metered-dose inhaler alone, with plastic spacer, or with cardboard tube

Study objective: To compare the lung delivery of chlorofluorocarbon-free salbutamol via a pressurized metered-dose inhaler (pMDI) alone, a pMDI with a small-volume plastic spacer, and a pMDI with a cardboard tube. Design: A randomized, single (investigator)-blind, three-way, crossover study. Setting: The Asthma and Allergy Research Group, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK. Participants: Twelve healthy volunteers aged 16 to 65 years. Interventions: The subjects were administered 400 mg of salbutamol via a pMDI alone, via a pMDI plus a small-volume plastic spacer, or via a pMDI plus a cardboard tube. Measurements and results: Blood samples for plasma salbutamol concentrations were taken at 5 min, 10 min, and 20 min after inhalation, to measure lung bioavailability as a surrogate for relative lung dose. The addition of the plastic spacer resulted in a significantly higher maximal plasma salbutamol concentration (CMAX) and average plasma salbutamol concentration (CAV) than the pMDI used alone. This amounted to a 1.48-fold (32%) difference (95% confidence interval [CI], 1.03 to 2.13) for CMAX and a 1.42-fold (30%) difference (95% CI, 1.01 to 2.00) for CAV. There was no significant difference in the CMAX or CAV comparing the addition of the cardboard tube with the plastic spacer or the pMDI alone. Conclusions: Using a chlorofluorocarbon-free pMDI with a plastic spacer produced statistically, but not biologically, significant greater lung delivery of salbutamol. If a spacer is required for reasons other than increasing delivered drug dose, then the addition of a readily available cardboard tube will fulfill many of the required functions with no expense to the patient.