Excipients: Their Role in Rational Formulation Design - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 90

Figure 2 Resulting cake structures after freeze-drying solutions of left: mannitol (crys-
talline) and right: sucrose (amorphous). Compare with Figure 9 in Chapter 5
for NaCl crystallisation from its solid solution in an amorphous sucrose matrix.
Bar length ¼ 100 mm. From Pafra Biopreservation, unpublished results
process cycle (e.g. temperature). Some examples of different ice and
product morphologies resulting from differences in the formulation
and cooling rates are shown in Figure 2. It must be stressed, however,
that both crystalline and amorphous states can yield acceptable prod-
ucts, albeit with different characteristics; some of them are summarised
below:
Crystalline formulations
Attractive visual appearance.
Known safe storage temperature, governed by equilibrium melting
points.
Plug may become ''powdery'' if subjected to rough handling.
Physical characterisation of a mixture can be complex.
Crystallised excipients offer no chemical protection to labile bio-
molecules.
Possibility of polymorphic and dehydration transitions during
storage.
Amorphous formulations
Cycle time can be shortened by choice of excipients with a high T g .
Safe storage temperatures are governed by T g that can be control-
led.
Hygroscopic, i.e. readily reconstituted into an aqueous solution.
Easily characterised by thermal analytical methods.
Glassy sheen sometimes found on plug surface is considered cos-
metically undesirable.