W. Richard Bowen and Nidal Hilal 4

6.2 THE AfM AS A fORCE MEASUREMENT TOOL IN PHARMACEUTICALS 177
(a)
Cantilever deflection (nm)
(b)
Motion of
lever
0
AFM cantilever
with drug particle
Sample
Particle approaching sample
Particle adhered
to sample
Particle detached
to sample
0
Relative veticle position of sample and particle (nm)
FIgure 6.2 (a) Schematic illustrating an AFM probe with attached drug particle coming
to, contacting with and being removed from a sample surface. (b) With data recorded
from such an event, the cantilever deflection can be converted to a force of the spring constant
if the lever is known and the relative positions to a true sample-particle separation if
the sensitivity of the microscope has been calibrated.
The influence of relative humidity on the forces between particles is
an important consideration in pharmaceuticals as this can strongly influence
the stability of a medicine through the mediation of solution-based
processes owing to surface adsorbed water. In addition, owing to the formation
of capillary bridges between particles with increased humidity,
this may cause aggregation. Hence, the effect of humidity has been the
subject of a number of AFM studies. Young and co-workers have shown
that drug cohesion increases at elevated humidity for some materials but
decreased for others, potentially as a result of long-range attractive electrostatic
interactions [20]. A variation in particle-contact morphology has
also been shown to cause similar behaviour with increasing humidity
[21]. The ability to record force data in controlled environments has been
extended to work in liquids, e.g. to rank interactions in model propellants
so as to simulate the environment within a pressurised metered dose
inhaler [22–24].