Drug particle size and lung deposition in COPD

Background: Drug particle size determines the lung deposition of aerosolised medicine in asthma,^[1] but is unknown in COPD. Aerosol deposition and its lung distribution have implications for the clinical efficacy of therapeutic aerosols. Aim: We determined the lung deposition of 3 particle-sizes of inhaled salbutamol sulphate (SS) in COPD patients, and compared to healthy subjects (HS). Methods: COPD patients (n=12, FEV₁= 70%pred) and HS (n=12, FEV₁= 107%pred), inhaled ^99mTc-radiolabelled SS monodisperse particles sizes (1.5, 3 and 6-µm) at two different (fast >60L/min and slow 30L/min) inhalation flows. Lung deposition was visualised using gamma-scintigraphic imaging and penetration index (PI) assessed how far into the lungs each inhaled aerosol penetrated. Results: Smaller particles achieved significantly better lung penetration (1.5m >3µm >6µm; p<0.05) at both fast and slow inhalation. Diseased COPD lungs led to decreased aerosol penetration versus healthy airways Conclusions: This is first data to precisely assess aerosol behaviour in COPD patients and to compare diseased versus healthy lungs. Striking differences in the deposition behaviour of different sized drug particles exist within COPD airways. Small aerosol particles inhaled slowly are more able to penetrate to all parts of the lungs. The airways obstruction in COPD patients do not allow aerosol particles to penetrate as far as in HS. [1]Usmani et al. Am J Respir Crit Care Med 2005; 172:1497–1504. Funded: UK-National Institute for Health Research CDF-2011-04-053.