Measurement of interaction forces between individual powder particles using an atomic force microscope

The atomic force microscope (AFM) was used to investigate the interaction forces between individual particles qualitatively as well as quantitatively. Lactose as a typical excipient for solid drugs was chosen as model substance. The interaction forces were determined between a single particle of crystalline lactose and a tablet of lactose. Their surface topography was characterized by AFM and scanning electron microscopy (SEM) in order to allow a quantitative assessment of the surface roughness and its influence on the measured forces. To analyze the representative surface segments, the minimum and maximum surface roughness of the lactose tablet is determined in dependence of the segment size. The contact area between the tablet and the particle of lactose was quantified by the tip estimation of Villarrubia. Interparticle forces were measured with force volume scans. They allow the determination of the three-dimensional surface structure and, simultaneously, a defined number of force curves in regular distances is taken.