The influence of carrier roughness on adhesion, content uniformity and the in vitro deposition of terbutaline sulphate from dry powder inhalers

The aim of this study was to establish a correlation between carrier characteristics and the dispersibility of drug from the blend. The influence of the roughness of a commonly used carrier material, lactose monohydrate, on the adhesion, dose uniformity, and aerodynamic properties of a model drug, terbutaline sulphate was investigated. Evaluation of adhesion was carried out with a mechanical sieve and an Alpine air-jet sieve. For the characterisation of lactose roughness, we used image analysis software. Aerodynamic evaluation of fine particle dose and emitted dose was obtained using a twin stage impinger. The study with the mechanical sieve demonstrated that at least 60% of drug adheres to lactose. The Alpine air-jet sieve assays showed there was a correlation between drug separation from a carrier by sieving and that obtained from longer in vitro deposition studies. Adhesion, blend homogeneity and stability are related to the surface roughness of the lactose used as carrier. There is a linear relationship between the parameters "fine particle fraction" and "roughness". A compromise between homogeneity and drug liberation must be found: a certain roughness is necessary to allow for drug adhesion and blend homogeneity, but if too high it will prevent drug liberation after inhalation. (C) 2004 Elsevier B.V. All rights reserved.