W. Richard Bowen and Nidal Hilal 4

188 6. NANOSCALE ANALySIS Of PHARMACEUTICALS by SCANNINg PRObE MICROSCOPy
type B, respectively. LTA was performed with a temperature ramp rate
of 10°C s �1 . Figure 6.8 shows the local thermal analysis of polymorphs B
and A with melting points observed between 140–146°C and 141–143°C,
respectively. The close range of melting points for polymorphs A and B
illustrates why bulk thermal analytical methods have difficulty distinguishing
between the two polymorphs. An interesting feature of the data
for polymorph A is the endothermic peak seen just above 100°C (marked
X in Figure 6.8b). This feature is seen in neither the bulk thermal analysis
of form A nor LTA of form B. This would suggest that this feature is a
result of the increased surface sensitivity of the localized measurements,
and that this endothermic peak is likely to be a result of adsorbed surface
water. This is consistent with form A being more hydrophillic than form
(a)
Sensor movement (μm) Sensor movement (μm)
(b)
1.5
0
–1.5
–3
1
0
–1
–2
(I)
(III)
20 60 100 140
Temperature (°C)
(I)
(III)
20
60
100 180
Temperature (°C)
FIgure 6.8 Localised thermal analysis of pure cimetidine polymorphs (a) B and (b) A.
Lines denoted (I) show the calorimetric data for a single point and dashed lines (II) show
the movement of the sensor during the measurement, corresponding to thermomechanical
analysis. Lines (III) and (IV) show similar data for other points on the samples. Reproduced
with permission [52].
(II)
(IV)
(IV)
(II)
1
0
1
0
–2
–4
–2
–2
Derivative power (μW deg –1 )
Derivative power (μW deg –1 )