The Dried Product - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 144

Figure 6 Heat flow DSC scan for freeze-dried sucrose, containing 0.5% w/w residual
water. Above T g , the sugar becomes vulnerable to more or less rapid collapse
and/or sucrose crystallisation, followed by melting at its equilibrium T m
The appearance of the DSC signal (resolution, shape and intensity)
depends on:
scan rate;
sample mass;
(solution) concentration and fill volume;
type of sample cell: open, sealed, pin hole;
instrumental sensitivity;
purge gas: helium, argon, nitrogen, dry air;
reference material: empty cell, sapphire, dry sand, etc.
Figure 7 represents cooling scans, showing both freezing and eutectic
crystallisation exotherms of aqueous b,b-trehalose solutions at identical
scanning rates (5 K min 1 ). 163 They illustrate the fundamental principle
of spectroscopy that resolution (signal width) is improved at the expense
of signal intensity. Similarly, an increase in the scanning rate increases
the recorded intensity but decreases the ability to discriminate between
closely spaced transitions.
DSC, as applied to the analysis of freeze-drying processes, can be
made more informative by the employment of variants, such as thermal
cycling and/or annealing. An illustration is provided in Figure 8. The
aim of the investigation was to resolve the origins of two apparent glass