Home / Documents & Brochures / Technical Briefs / Freeze Drying:

2(a). Sublimation Considerations

Table of Contents:

1. Introduction
2. Principle
(a) Sublimation Considerations
(b) Freezing Considerations
3. Practice

The figure 1. shows the phase diagram for the ICE/WATER/WATER VAPOUR system. The curve A-B is termed the Sublimation Curve, at which the Solid and Vapour are in equilibrium. Similarly for Curve B-C the Melting Curve and B-D the Evaporation Curve, terminating at C-P the Critical Point. The point of intersection of the Curves T-P is called the Triple Point, at which the three phases exist in equilibrium. It has a unique value for pressure and temperature, and is a reference point, for which the Celsius temperature scale is now defined.

Ice/Water/Water Vapour System Phase diagram

Figure 1.

Sublimation Pressure

Figure 2.

It should now be apparent that for any pressure in a system below the Triple point pressure, we can change water from the solid to vapour phase without the liquid phase being present, if the temperature at which we are allowed to do this does not have any restrictions.

In the freeze drying of Biological Specimens there are however limitations on the initial temperature to which the specimen should be allowed to warm when drying is commenced.

In practise therefore, the system pressure (relative vacuum) used, is much lower than the Triple Point pressure. The Fig. 2 gives an indication of the sublimation pressure (Saturated Vapour pressure at differing temperatures, and satisfactory freeze drying will be determined by this, and the partial pressure (Unsaturated Vapour pressure) of the water vapour in the vacuum system, which is required to be lower. The right hand scale gives an indication of Sublimation rates, (assuming partial pressure of H20 is not limiting) which are totally temperature dependent.

In any Biological Specimen freezing protocol, involving water, the re-crystallisation of ice is a factor for consideration. However, at the temperature at which this phenomena is considered to being (-130oC) the sublimation rate is of the order of 1 x 10-5 nm/sec., and freeze drying times may be inordinately long. Also the constraints on the vacuum system would be substantial as the Saturated Vapour pressure of the ice at this temperature is of the order 1 x 106Pa.(7.6 x 10-9Torr).

While we may now deduce that we can freeze dry up to the Triple Point temperature and associated pressure, between this point and the previously mentioned re-crystallisation point will be an optimum range of temperature, which may be used for, freeze drying our Biological Specimens.

Indications have been made that while there is ice crystal growth at temperatures warmer than -130oC, there is no significant difference in the ice crystal growth between specimens held at -40oC and those at -80oC, and it has been suggested that the transition from microcrystalline to coarse crystalline ice may be considerably slowed in the presence of an organic matrices, found in Biological Specimens.

A general conclusion is that while freeze drying at temperatures of the order of -20oC, -30oC will produce poor results, freeze drying at temperatures of the order of -60oC, -70oC, will be satisfactory. We may consider therefore, having taken account of these factors, that initial freeze-drying at -60oC could be a suitable optimum. This temperature and the associated vacuum required being readily achievable.

 Page 3 of 5: 1 2 3 4 5