Abstract

Maximising the rate of drug delivered in particles small enough to reach the lower respiratory tract from jet nebulisers may allow treatment times to be reduced and thus improve the acceptability of this form of treatment, particularly in very young patients. The role of various technical factors such as driving gas flow (DGF) in determining the rate of drug delivery was studied by constructing a model to simulate the respiratory pattern of individuals with different tidal volumes using a Starling ventilator and filter. Sodium cromoglycate was nebulised under a variety of operating conditions and the dose deposited on the filter was assayed. Tidal volumes of 50 and 400 ml were used at a frequency of 32 breaths per minute. Increasing the DGF from 4 to 8 l/minute produced a 264% increase in the rate of drug output but only a 32% increase in aerosol concentration. The mass of drug contained within droplets less than 5 microns increased from 26.8% to 70.8% of the total. The resultant increase in rate of drug delivery to the filter was 34% for a tidal volume of 50 ml and 79% for a tidal volume of 400 ml though the dose contained within droplets less than 5 microns increased by 4-fold at 50 ml tidal volume and by more than 5-fold at the higher tidal volume. Halving the solution concentration halved the rate of drug delivery. Increasing the tidal volume 8-fold from 50 to 400 ml resulted in an increase in the rate of drug deposition upon the filter of only 2.2 to 3-fold depending upon the DGF so that substantially more drug per ml inhaled was delivered at the lower tidal volume. These results are explained by considering factors that influence the rate of drug delivery. At low tidal volumes the rate of drug delivery at a given respiratory rate is dependent on the tidal volume and aerosol concentration. At high tidal volumes it is dependent upon aerosol concentration and volume of available aerosol and is essentially independent of tidal volume.