W. Richard Bowen and Nidal Hilal 4

184 6. NANOSCALE ANALySIS Of PHARMACEUTICALS by SCANNINg PRObE MICROSCOPy
FIgure 6.5 A sequence of 10 �m � 10 �m AFM images of the (001) face of a paracetamol
crystal during incubation in paracetamol solution. In image (a) time t � 0 s, (b) t � 60 s,
(c) t � 118 s, (d) t � 176 s, (e) t � 234 s and (f) t � 292 s. Figure reproduced with permission [46].
shown in Figure 6.5, and illustrates that the growth steps of crystallisation
over 4.8 h are curved in appearance, indicative of crystal growth via
the screw dislocation mechanism. AFM images of the (001) face of another
paracetamol crystal during incubation with 4 mol% acetanilide over time
are shown in Figure 6.6. The defects in the crystal surface form weak
points, leading to deepened holes (one hole is highlighted by a black
arrow in Figure 6.6) over 12 h, indicating that the dissolution occurs both
laterally and towards the crystal core [46]. Images during incubation with
4 mol% metacetamol showed that the steps formed were significantly
smaller and pointed in appearance (image not shown here). These features
were ascribed to ‘pinning’, an effect caused when additives adsorb
onto the steps and force them to grow between the impurities [46].
From our consideration of AFM as a force measurement tool, it is clear
that the probe is sensitive not only to topography but also to the magnitude
and nature of the forces experienced by the probe. Consequently,
whilst imaging, if such sensitivity can be mapped also, it becomes possible
to produce alongside topography data sensitive to a particular surface
property (e.g. adhesion, harness etc.). For example, during the commonly
employed tapping mode imaging [47], where the AFM cantilever is oscillated
at its resonant frequency and intermittently contacts a sample surface
at the bottom of each oscillation cycle, the phase of the oscillation as well as