Friction measurements on particles adhered to compacted powder surfaces have been undertaken by the centrifuge technique to investigate the influence of the variations in the chemical structure of a series of salts of salmeterol. Two mathematical models have been used to evaluate the experiments, and the coefficient of static friction, the friction force and the theoretical shear force on compacted powder surfaces of lactose monohydrate and salmeterol xinafoate have been derived. The results show differences in the mechanism of friction and also divide the five compounds into comparatively hard (salmeterol base and sulfate) and soft (salmeterol 4-chlorobenzoate, salicylate and xinafoate) materials. The hydrophilic nature of the particulate material was found to be indicative of its friction properties on a hydrophobic surface, and vice versa. The ability of a material to adsorb water is reflected in the relative hydrogen bonding coefficient (Hansen-solubility parameter), and a linear relationship was found between this coefficient and the friction force obtained. Water can act as a lubricant reducing the friction between two surfaces. The friction between like materials in contact was found to be minimal. The results also imply that no general descriptor of the chemical structure of related compounds, which would allow the prediction of friction properties, exists. Instead, the descriptor needs to be chosen according to the properties of the surfaces in contact, or friction experiments have to be performed.