W. Richard Bowen and Nidal Hilal 4

6.3 AfM IMAgINg-bASEd STUdIES 183
6.3 AFM IMAgINg-BASed STudIeS
As a microscopy, AFM is perhaps better known for its ability to image
surfaces at nanometre resolution in a variety of environments than as a
force measurement tool. As a material under study can be exposed to
environmental stresses (temperature, humidity, solvents etc.), it can often
be in a dynamic state and hence, as long as the kinetics are not too rapid,
AFM is able to provide a dynamic view of surface-mediated processes
(unless employing advanced video rate imaging AFM [42], a typical
1 �m � 1 �m image takes approximately 30 s to acquire). This approach
has found effective applications in pharmaceuticals in the study of environmental
stress on the surface properties of formulations, drug release
from erodible materials and crystallisation phenomena.
Price and Young [43] have studied the real-time effects of changes in
relative humidity (RH) on spray-dried lactose using environmentally
controlled AFM. The lactose was imaged at 0%, 30% and 58% RH for 4, 2
and 22 h, respectively. Recrystallisation of amorphous lactose, promoted
by the presence of water, was observed at 58% and 75% RH, although
only some of the particles were shown to undergo nucleation and crystal
growth. The AFM data was combined with traditional approaches
such as X-ray powder diffraction, differential scanning calorimetry and
dynamic vapour sorption and was shown to have significant potential
for studies of the nucleation and crystallisation processes of amorphous
material [43].
Li and co-workers have utilised contact mode AFM imaging in air to
image a series of partial dissolutions on the (010) face of paracetamol
[44]. From the AFM images of the (010) face of acetaminophen crystals
treated with alternative dissolution solvents, different etching patterns
were observed. These different etching patterns were speculated to be a
result from the surface diffusion of the crystal molecules desorbed during
the dissolution process and by the mutual interaction between the
solvent and crystal molecules. AFM has similarly been employed to
visualise the effect of dissolution media on various polymeric systems
designed to achieve a specific drug-release profile [45].
It is widely known that pharmaceutical additives and impurities in
drug formulations can affect drug crystal growth, morphology and potential
drug efficacy. This may be achieved deliberately to control crystal
habit or an undesirable consequence of contamination. By understanding
the degree to which impurities affect these critical formulation parameters,
drug delivery systems can be developed more effectively. AFM has
the capability to study drug crystal changes in real time, as demonstrated
by Thompson et al. in the study of paracetamol in the presence of impurities,
acetanilide and metacetamol using AFM in liquid [46]. A series of
real-time AFM images of the (001) face of a native paracetamol crystal are