Surface roughness contribution to the adhesion force distribution of salmeterol xinafoate on lactose carriers by atomic force microscopy.

Adhesion force distributions of silica spheres (5 and 20 microm) and salmeterol xinafoate (4 microm) particles with inhalation grade lactose surfaces and spin coated lactose films were determined by atomic force microscopy (AFM) to investigate the influence of surface roughness on the force distributions. The roughness of lactose particles and films was determined by both AFM and confocal microscopy (CM); the lactose particles showed RMS R(q) values between 0.93 and 2.2 microm. The adhesion force distributions for silica and SX probes were significantly different for the different lactose carriers and broad, e.g., the adhesion force distribution between a 5 microm silica sphere and lactose particles ranged from 5 to 105 nN. This contrasted with distributions on smooth spin coated lactose films (RMS R(q) of 0.28 nm) which were not significantly different and were narrow, e.g., the adhesion force distribution between a 5 microm silica sphere and spin coated lactose films was between 42 and 68 nN. In addition, no significant difference in adhesion force distribution occurred with silica probe size on the lactose carrier surface. The use of X-ray photoelectron spectroscopic analysis confirmed that the lactose surfaces were free of impurities that might contribute to variation in adhesion. Although the almost atomically flat films showed some adhesion variability, the surface roughness of the lactose particles was a major contributing factor to the broad distributions seen in this study. (c) 2005 Wiley-Liss, Inc.