Chemistry Reference
In-Depth Information
rates for different components may differ by orders of magnitude.
Problems may also arise from molecular interactions that inhibit
(poison) the crystallisation of individual components. This phenomenon
has, however, been usefully employed in a full characterisation of the
glass properties of mannitol, when its crystallisation is interfered with
(poisoned) by the addition of low concentrations of sorbitol.
57
In the production of solid pharmaceutical preparations, it is important to
be aware of the identities of polymorphs that might be formed during the
drying process, or during any later processing steps, e.g. milling, compres-
sion, extrusion.
131
The pressure-induced formation of specific solvates with
superior stabilities has also been reported, e.g. for paracetamol.
132
In situ hydrate crystallisation, facilitated by residual water under certain
storage conditions can, however, also be of practical value. This has been
described by Aldous et al.
100
for freeze-dried a,a-trehalose and raffinose.
The trehalose preparation contained 8% residual water, which gave it a
T
g
of 311C. After overnight storage at 821C, a T
g
of 791C was recorded,
followed by a crystal-melt endotherm at 971C, characteristic of trehalose
dihydrate. The results are shown in the form of differential scanning
calorimetry (DSC) heating traces in Figure 3. Similar experiments, per-
formed on raffinose, containing 3.7% residual water, produced qualita-
tively identical results. Overnight storage a few degrees below the melting
point of the pentahydrate,
led to the disappearance of a previously
1mW
1
3
2
240
260
280
300
320
340
360
380
400
Temperature/K
Figure 3 Successive DSC heating scans for air-dried trehalose containing 8% residual
water. 1: first heating scan; 2: heating scan after overnight exposure to 355 K
(821C) and recooling to 2303, and 3: heating scan after melting and recooling
to 230 K. Note the shift in T
g
accompanying crystallisation. Reproduced with
permission from Aldous et al.
100
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