On the physical transformations of processed pharmaceutical solids

Atomic force microscopy Phase Imaging, an adaptation of Tapping Mode AFM was used to visualise physico-mechanical variations on the surface of crystalline materials after being subjected to mechanically induced lattice damage. Large crystals (100–500 μm) of lactose were nucleated on AFM sample stubs, imaged and subjected to a milling process. The milled samples were then imaged at specific humidity using Phase Imaging. Phase and Amplitude images of the re-crystallised lactose suggested an ordered crystalline state with multiple platelets present across the surface. In comparison, the morphology and surface properties after a 1-min mill time suggested milling had a dramatic effect on the surface characteristics of the re-crystallised lactose. Phase and Topographical imaging during exposure to elevated humidities (70% RH) indicated both morphological and physico-mechanical changes that may be linked to surface amorphous re-crystallisation.