Nanoscope 5.12b control software

The adhesive or cohesive force between each colloidal probe and the dominant face of a smooth crystal of each relevant material was measured with force-volume mode AFM using a Multimode AFM, J-type scanner, Nanoscope IV controller and Nanoscope 5.12b control software (all from Veeco, Cambridge, UK). At least 256 (16  16) individual force curves were collected over a 10 µm  10 µm area of the crystal substrate with a z-scan rate of 4.07 Hz and a nominal compressive loading of 11.6 nN. Humidity within the sample area of the AFM head was maintained at 26ºC (±2ºC) and 35% RH (±3%), using a previously described method (Young et al., 2003) . The cohesive force between each colloidal probe and the crystalline substrate of the same drug was measured before and after the adhesion measurements, to ensure there had been no changes in the drug particle.
Force-volume data were processed using custom software to extract the force of adhesion/cohesion from each of the force curves. This calculation was performed using the nominal cantilever spring constant of 0.58 N.m -1 (rather than the measured spring constant of each individual probe) as the comparison of the cohesion and adhesion of the same probe in the CAB method eliminates the effects of cantilever-to-cantilever spring constant variation (Hooton et al., 2006) .