Press-on forces are thought to play an important role in the effects of drug content and added fine lactose particles on the dispersion behaviour of adhesive mixtures for inhalation. The mechanical stress experienced by the drug particles during the mixing process due to such forces can be assessed by a change in the apparent solubility of the drug in the mixture, as has previously been shown for salmeterol xinafoate (SX). The apparent solubility of SX was therefore used to study the effects of changes in the formulation variables mentioned on the occurrence and relevance of press-on forces. An increase in salmeterol content and the addition of ‘fine lactose fines’ (FLF, X50 = 1.95 µm) resulted in a lower apparent solubility of SX after prolonged mixing, whereas ‘coarse lactose fines’ (CLF, X50 = 3.94 µm) did not. These findings do not support the previously proposed hypotheses that higher fine particle contents increase the susceptibility of drug particles to press-on forces, and that CLF may act as a buffer between colliding particles to reduce the susceptibility of drug particles to press-on forces. However, it can be reasoned that a direct relationship between press-on effects and apparent solubility does not necessarily exist, especially when the carrier surface is covered by a multi-particulate layer. Therefore, the hypotheses cannot be conclusively rejected. It is shown, however, that the apparent solubility of salmeterol xinafoate is a useful measure for the characterisation of carrier-based dry powder inhalation formulations.