In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices

Abstract

Metered-dose inhalers (MDLs) are currently being reformulated to contain hydrofluoroalkanes (HFAs), which do not damage the Earth's ozone layer. As different formulations of inhaled drugs may behave differently when used with spacer devices, we wished to determine the amount of salbutamol available for inhalation from a conventional metered-dose inhaler (Ventolin®) and a new HFA-containing formulation (Airomir®), when used with two different spacers. A glass multistage liquid impinger was used to determine the amount of salbutamol delivered from the inhalers used with the Aerochamber® and the Nebuhaler® spacer devices. High speed video-recordings of inhaler actuation into air were made, and the speed of the aerosol and the aerosol cloud volume were measured. More salbutamol in small particles (<5 μm) was delivered from the Airomir® MDI than the Ventolin® MDI, when used with the Aerochamber® (40.4 (95% confidence interval (95% CI) 31.2-49.6) versus 19.5 (19.0-20.0) μg) and the Nebuhaler® (42.1 (36.3-47.9) versus 24.6 (23.3-25.8) μg). The aerosol cloud from the Airomir® MDI was slower than the Ventolin® aerosol, and 60 ms after actuation had travelled 186 mm, whereas the Ventolin® aerosol had travelled 320 mm. At the same time, the Airomir® aerosol occupied a smaller volume than the Ventolin® MDI (251 (213-288) versus 695 (608-782) cm3). The hydrofluoroalkane formulation delivers more salbutamol than the conventional formulation when used either with the Aerochamber® or Nebuhaler® spacer. This may be because less drug is deposited in the spacer from the hydrofluoroalkane formulation, which is emitted from the metered- dose inhaler at a slower speed and occupies a smaller volume than the conventional formulation. The observed difference in drug delivery may be important for patients changing formulations, and in severe asthma, where high doses of salbutamol may be administered through a spacer.