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In their 1906 paper to the Académie des Sciences in Paris (almost a century
ago), Bordas and d’Arsonval [1] demonstrated for the first time that it was
possible to dry a delicate product from the frozen state under moderate
vacuum. In that state it would be stable at room temperature for a long time
and the authors described, in a set of successive notes, that this technique
could be applied to the preservation of sera and vaccines. Freeze-drying was
then officially borne, despite its having been in use centuries ago by the Incas
who dried their frozen meat in the radiant heat of the sun in the rarified
atmosphere of the Altiplano.
However, we had to wait until 1935 to witness a major development in
the field when Earl W. Flosdorf and his coworkers [2] published some very
important research on what they called, at the time, lyophilization (this
name was derived from the term lyophile coming from the Greek luoB and
jilein, which means ‘‘likes the solvent,’’ describing the great ability of the
dry product to rehydrate again). Freeze-drying had then received a new
name that has been in current use since, together with cryodesiccation.
Many authors, in different comprehensive books dedicated to freeze-
drying, have already described in full detail the scientific history of this
I. BASIC FREEZE-DRYING
Figure 7 Differential thermal analysis and impedance (1000 Hz) of pure glycerol.
1. Method
Small samples of liquid (0.5 to 1 cm3) are deposited in open aluminum
capsules and frozen down to liquid nitrogen temperatures under well-
controlled conditions (generally a two-step freezing: down to 20 C in
10 min with a 5–6 h equilibrium time at this temperature followed by
quenching to 196 C). The capsules are then ‘‘activated’’ by gamma
2. Results
It is generally assumed that the thermoluminescence centers are located
preferentially in the defects of the crystalline network and that those defects,
in turn, are a mere reflexion of the structure of the original liquid. We can,
thus, expect to know a little more about our starting solutions.
Figure 13 shows the thermoluminescence curves for pure H2O and
D2O. For H2O they confirm prior measurements made by Grossweiner and
Matheson [8]. Several major peaks can be identified. We can also see that for
D2O the level of emission is much higher than for H2O. Figure 14 a and b
shows the emission spectrum for different regions of the rewarming curve.
At that point we are still unclear as to the deciphering of this emission
but we can assume that the lower peaks (at 158 C for H2O, 155 C
for D2O) are linked to the internal structure of the water molecule itself
since they show such a major isotopic dependence. Conversely, the higher
temperature emissions (from 120 C to 80 C) appear to be more directly
connected to the structure of the crystalline lattice itself and, more particu-
larly, to the state and position of the network defects.
We got some support for this idea when we discovered that, in glycerol
and in glycerol/water systems, the main luminescence emission did coincide
with the temperature range during which structural events occur and, more
precisely, when the vitreous transformation takes place. Figures 15 and 16
present these data. Thus, we are inclined to believe that the application of
this technique to numerous systems presenting low-temperature evolutions
such as sugar, polymers, and alcohols might be of interest.
This is one of the reasons why we could not resist applying low-
temperature thermoluminescence to dilutions of the type used by homeo-
pathy. Indeed, the scientists who have been working in this field have often
Numerous books and papers have been written on the physics of primary
and secondary drying. In the present book, G. W. Oetjen reviews quite
extensively the different parameters involved. Therefore, it is pointless deal
with this topic in the introductory chapter. However, we would like to stress
one single point that has not always been clearly understood: the central role
of the operating pressure. Indeed, as we have shown in Figure 2, freeze-
drying deserves an accurate and continuous control of the pressure in the
chamber during the whole operation.
With the exception of vacuum freezing (or ‘‘snap’’-freezing), the initial
cooling is always done at atmospheric pressure, sometimes in a
separate cabinet.
Primary drying, to the contrary, is performed under vacuum. Whereas
in the young days of the technique it was felt by more specialists that
the higher the vacuum the better the process could be, it was shown
by Neumann [10] and Oetjen et al. [11] that throttling the water
vapor flow between the chamber and the condenser was increasing
the speed and efficiency of the operations. Later on, Rieutord and
I patented the air injection process [12], which could be applied to
any equipment whether the condenser coils were placed in a separate
REFERENCES