Chemistry Reference
In-Depth Information
Table 1 Eutectic data of aqueous phosphate solutions
T
e
(1C) C
e
(1) M C
e
(2) M Crystal type
C
e
(1)/C
e
(2)
NaH
2
PO
4
9.7
3.42
NaH
2
PO
4
.2W
Na
2
HPO
4
0.5
0.11
Na
2
HPO
4
57 (0.72)
a
NaH
2
PO
4
-Na
2
HPO
4
9.9
3.42
0.6
NaH
2
PO
4
.2W
Na
2
HPO
4
.12W
KH
2
PO
4
2.7
0.92
KH
2
PO
4
K
2
HPO
4
13.7
2.85
K
2
HPO
4
.6W
0.48 (0.72)
a
KH
2
PO
4
-K
2
HPO
4
16.7
1.30
2.70
KH
2
PO
4
K
2
HPO
4
.6W
W, water; (1), mono Na or K salt and (2), di Na or K salt.
a
Corresponds to pH 7 buffer ratio.
Data from Van den Berg and Rose
55
and Murase and Franks.
56
peritectic point, water of crystallisation might not be completely removed
during primary drying, thus leading to stability problems during storage
of the ''dried'', but not dry product.
An example of a previously unknown hydrate was recently reported
for mannitol, a commonly used excipient in pharmaceutical freeze-
drying. It was formed inadvertently during the particular drying proto-
col used.
57
It was identified as a hydrate by X-ray diffraction, differential
scanning calorimetry (DSC) and thermogravimetry, and it will be fur-
ther discussed in a later chapter.
In Chapter 4, reference was made to the general phenomenon of
undercooling and the process of nucleation, particularly as it affects the
crystallisation of ice. The discussion will now be broadened because any
solid phase that separates from a liquid mixture is subject to the same
physical laws that apply to water. The phase rule, which predicts the
equilibrium phase coexistence in solid and liquid mixtures, does not take
into account the rates at which solid phases can grow within the liquid
solution. These rates are governed by the theory of nucleation as
discussed in the previous chapter. Since nucleation is a stochastic process
and, in practice, can also be affected by cosolutes or even by trace
contaminants in a solution, it is impossible to ascribe definite nucleation
or crystallisation temperatures to particular substances. As a general
rule, however, spontaneous crystallisation at the eutectic temperature is
rare; hence, that some degree of transient supersaturation is common.
An example of such a process, in the form of a simulation, is illustrated
for an isotonic saline solution in Figure 4 (Pikal, personal communica-
tion). In this example, a cooling rate of 1.251min
1
is applied, and
freezing is assumed to occur at -151C. On continued cooling, as the
liquid water content decreases, the NaCl concentration correspondingly
increases. No discontinuity (crystallisation/precipitation) is observed at
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