Abstract
The main objective of this study was to compare the in vitro delivery of salbutamol from a chlorofluorocarbon(CFC)-propelled pressurised metered-dose inhaler (pMDI) versus a newly developed hydrofluoroalkane(HFA)-propelled pMDI through various spacers. In addition, we aimed to study the effect on bronchodilator response when using an optimal pMDI/spacer combination for aerosol delivery compared to a suboptimal combination. Particle size distribution and output from salbutamol pMDIs containing either CFC propellants (Ventolin) or HFA propellants (Airomir) were measured using a multistage liquid impinger (MSLI) and compared to that through both detergent-coated (non-static) or untreated (static) large volume (Nebuhaler, Volumatic) and small volume (Aerochamber) plastic spacers. Flow-volume curves (FEV1) were obtained from twelve asthmatic children with known significant bronchodilator response (8 males), aged 13-17 years, randomly inhaling salbutamol from a CFC-pMDI through a static spacer (Nebuhaler) and from an HFA-pMDI through a non-static spacer (Nebuhaler). In vitro output of particles in the respirable range (< 6.8 microns) from HFA-pMDIs was significantly higher than that from CFC-pMDIs using various spacers. Removal of electrostatic charge increased output from CFC- and HFA-pMDIs through all spacers by 17-82%. The mean (SD) bronchodilator response after inhalation of salbutamol from a CFC-pMDI through a static spacer was 7.1% (6.3%) compared to 17.5% (7.9%) after inhalation from an HFA-pMDI through a non-static spacer (p = 0.002). Use of a newly developed HFA-propelled pMDI greatly improves drug delivery through spacers compared to a CFC-propelled pMDI. However, electrostatic charge in plastic spacers remains the key determinant limiting delivery of salbutamol from a pMDI through spacers, and can be reduced by soaking the spacer in a household detergent. Using an optimal pMDI/spacer combination leads to a significantly improved bronchodilator response.
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