Early lung absorption profile of non-CFC salbutamol via small and large volume plastic spacer devices

Br J Clin Pharmacol. 1998 Jul;46(1):45-8. doi: 10.1046/j.1365-2125.1998.00041.x.


Aims: To evaluate the lung dose of a non-CFC salbutamol metered dose inhaler (MDI) formulation via three commonly used plastic spacer devices, of both large and small volume, compared with the MDI used on its own.

Methods: Ten healthy volunteers were studied in a randomized single (investigator) blind crossover design. Single 1200 microg nominal doses of salbutamol from a non-CFC MDI (Airomir), as 12 sequential 100 microg puffs over 6 min, were delivered from the MDI alone and via two large volume spacer devices (Nebuhaler, Volumatic), and a small volume spacer (Aerochamber). All spacers were prewashed prior to each study day and mouth rinsing was performed after each drug sequence. Plasma salbutamol was measured at 5, 10, 15 and 20 min, with calculation of maximum (Cmax) and average (Cav) concentrations. This lung dose was assessed using the early lung absorption profile of salbutamol in the first 20 min after inhalation.

Results: Both of the large volume spacers, the Nebuhaler and the Volumatic, delivered significantly more salbutamol than the MDI alone. For Cav this amounted to a 2.07-fold difference (95% CI 1.48-2.90) between Nebuhaler vs MDI, and a 1.49-fold difference (95%CI 1.19-1.87) between Volumatic vs MDI. The Nebuhaler also produced greater deposition than either the Volumatic or the Aerochamber spacers; Nebuhaler vs Volumatic: 1.39-fold difference (95% CI 1.09-1.76), Nebuhaler vs Aerochamber: 1.63-fold difference (95% CI 1.20-2.21). There were no significant differences between the Aerochamber and the MDI alone.

Conclusions: Using the early lung absorption profile, for administration of the same nominal dose, both of the large volume spacers (Nebuhaler and Volumatic) but not the small volume spacer (Aerochamber) delivered significantly more salbutamol than the MDI alone. The Nebuhaler also produced greater delivery than either the Volumatic or the Aerochamber spacer devices. Our results show that whilst lung delivery of non-CFC salbutamol MDI is improved by the use of a plastic spacer, there may be appreciable differences in performance, particularly between large and small volume devices.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Administration, Inhalation
  • Adult
  • Albuterol / administration & dosage
  • Albuterol / pharmacokinetics*
  • Asthma / drug therapy
  • Asthma / metabolism
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacokinetics*
  • Equipment Design
  • Female
  • Humans
  • Lung / metabolism*
  • Male
  • Nebulizers and Vaporizers*
  • Single-Blind Method


  • Bronchodilator Agents
  • Albuterol