W. Richard Bowen and Nidal Hilal 4

176 6. NANOSCALE ANALySIS Of PHARMACEUTICALS by SCANNINg PRObE MICROSCOPy
500 nm
AFM cantilever
Drug particle
FIgure 6.1 SEM image of the end of an AFM cantilever to which a single drug particle
has been attached. The lower extremity of this particle forms the contact region with a sample
surface being studied within the AFM.
Having manufactured a particle probe, the forces of interaction of this
probe with a surface are recorded. Figure 6.2 illustrates a schematic of a
force curve and the main stages in acquiring such single-particle adhesion
data. If such data is to be quantified in terms of force, then the
spring constant of the AFM lever needs to be determined to enable calibration
[16]. To ease comparisons between different-particle adhesion
measurements, it is important to control key environmental factors such
as humidity and to keep such instrument parameters as maximum presson
force, contact time, particle approach and retract speed constant.
Many researchers have now exploited this approach to explore particle
interactions between drug and excipient particles and the components
of delivery devices. Louey et al. used this approach to measure pulloff
forces between a model colloidal silica probe and lactose particles
suitable for use as carriers in a DPI [17]. AFM has also been used to
rank the force of interaction of salbutamol with materials relevant to its
inhaled delivery in the following manner, glass � lactose � salbutamol �
polytetrafluoroethylene (PTFE), showing that on PTFE tribocharging
occurred following repeated contact [18]. Using AFM in this way has
also revealed the effect of inducing amorphous content on the surface of
particles of the drug zanamivir, where an increase in its affinity with a lactose
carrier surface was observed [19]. Such surface amorphous material is
important from a pharmaceutical perspective as this will be more soluble
and probably less stable than a crystalline form of the drug, and hence can
cause desirable (or undesirable) effects in terms of increased amounts of
drug delivered on administration and stability problems in a medicine.