Characterization of the surface physico-chemical stability of materials directly applicable to inhalation therapy

Atomic force microscopy (AFM) has been used to investigate the surface properties of mechanically processed respirable sized drug particles. Phase imaging, an auxiliary technique of conventional intermittent contact mode Tapping Model AFM imaging, was employed to differentiate the physico-mechanical variations on the processed surfaces of model salbutamol sulphate drug crystals. Samples were produced by cumulative milling of crystals formed by conventional batch crystallisation. With increased periods of milling, specific regions on the salbutamol sulphate crystals showed increased variations in phase lag (<30°), which were independent of topographical induced phase changes. These regions, not generally observed on nonmilled samples, suggested a surface induced change to the physico-mechanical properties of the processed crystals. The surface regions of increased phase could possibly be associated with the formation of surface disorder, which could be amorphous in nature.