The Dried Product - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 162

Figure 13 Relationship between kinetics of chemical processes, measured as t 1/2 versus
(T - T o ) of freeze-dried hGH, formulated with stachyose and trehalose, with
protein:sugar weight ratios of 1:1, 3:1 and 6:1, at 40 and 501C. Symbols:
¼ chemical deterioration and m ¼ hGH aggregation. Redrawn with changes
from M.J. Pikal, private communication of unpublished results
Possibly several of these remaining puzzles are interrelated. Until cause-
and-effect relationships can be established, there remain uncertainties
about predictions of long-term behaviour of freeze-dried preparations,
based solely on physical measurements in real time. For safety consid-
erations alone, therefore, reliable predictions will presumably have to
involve laborious and time-consuming real-time chemical assays.
11.11 Reconstitution at Point of Administration
The delivery of freeze-dried preparations can be performed by different
routes: oral, nasal, anal, pulmonary, transdermal and parenteral. Of
these routes, some do not require any treatment of the drug before it is
administered, e.g. in the form of powders or tablets or in inhaling
devices. For parenteral administration, however, whether by injection or
infusion, the freeze-dried cake must be returned to a liquid state, a
process referred to as ''reconstitution''. The main vehicle will normally
consist of ''water for injection'' or a solution, the concentration of which
will establish isotonicity. The time required for the complete dissolution
of the cake may in some cases be critical and should therefore be known.