The relationship between surface coverage and in vitro respirable fraction often referred to as fine particle fraction (FPF)-of dry powder inhaler (DPI) formulations for the therapy of asthma was investigated using an artificial lung, the next generation impactor (NGI). Therefore mixtures with 100%, 50% and 25% calculated surface coverage of physically and chemically modified glass beads as model carrier and spray dried salbutamol sulfate as active pharmaceutical ingredient (API) have been prepared. In any of these cases the actual surface coverage was lower than the calculated surface coverage as a certain amount of API particles adheres to the mixing container wall instead of the glass bead surface. Moreover, API particles detach from the glass bead surface during capsule filling and transport resulting in even lower true surface coverage at the moment when the NGI experiments are performed. When investigating the FPF this true surface coverage has to be taken into account. The FPF increased more or less linearly with increasing surface coverage of the surface modified glass beads but the slopes of the lines are different depending of the carriers used. This can be attributed to the distribution of active sites on the glass bead surface that is individually depending on the surface modification applied and the processing time. However the influence of surface coverage on FPF is also influenced by the choice of the carrier particles. Compared to untreated glass beads physically modified glass beads show increased FPFs whereas chemically modified glass beads show lower FPFs. (C) 2014 Elsevier B.V. All rights reserved.