W. Richard Bowen and Nidal Hilal 4

6.4 MICRO- ANd NANOTHERMAL CHARACTERISATION wITH SPM 185
FIgure 6.6 A sequence of 10 �m � 10 �m AFM images of the (001) face of a paracetamol
crystal in paracetamol/4 mol% acetanilide solution. The dissolution of step one
is followed by a black arrow on each image. Image (a) is taken 11.5 min after addition of
paracetamol/4 mol% acetanilide solution. Images (b–f) are taken at the following times
after image (a): (b) t � 146 s, (c) t � 290 s, (d) t � 436 s, (e) t � 582 s and (f) t � 728 s. Figure
reproduced with permission [46].
the topography can be recorded. Phase images are obtained by measuring
the phase lag between the signal that drives the cantilever-tip oscillation
and the output signal of the cantilever oscillation (will differ more to the
original cantilever-tip oscillation if the sample surface is soft and viscoelastic
due to greater energy lost to the sample). The use of phase imaging
alongside topographical imaging is particularly useful for studying drug
polymorphs phase-separated systems and drug-excipients systems as it
can be used to map out a profile of materials with different mechanical and
physicochemical properties [48, 49].
6.4 MICro- ANd NANoTherMAl
ChArACTerISATIoN wITh SPM
Knowledge of the distribution and physical form of a drug in its
formulation is important in determining its overall performance and
can further our understanding into bioavailability issues in medicines.
Classically, one of the main tools used to identify the form a drug takes
within a formulation and the interactions between its components is