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Active Freeze Drying - The new standard

Article index
 Parameters influencing the Freeze Drying process
 Much higher capacities
 No handling / no contamination
 Active Freeze Drying applications
 Pharmaceutical applications
 Food applications
Freeze drying (Lyophilisation) is a technique where a solvent (normally water) is being removed under very low pressure conditions. Unlike vacuum drying - with pressures down to 20 mbar - freeze drying is performed at pressures < 6 mbar.
The reason is physically: below 6 mbar water does not exist anymore as a liquid; it is either a solid or a gas. As the removal of water is accomplished, the water is sublimated, e.g. direct transfer from a solid state into a gaseous state.

Freeze Drying

The common technique of freeze drying in the Food- and Pharmaceutical industry is by using trays. The liquid to be freeze dried is poured on trays (normally up to 1 m2 and 1-2 cm height). The trays are driven with a trolley into the freeze drying chamber.
The other technique, where trays are applied as well, uses a grid in which dozens of vials are placed. Here each vial contains an exact amount of liquid, thus at a given concentration will end up to an exact amount (mg.) of powder. These vials are closed after operation with a stopper. Upon use an isotonic liquid is injected into the vial creating a ready to use active solution for injection in situ.

Parameters influencing the Freeze Drying process

There are different parameters which are influencing the lyophilisation process.
Due to the low pressure, the volumes which need to be removed are enormous. At atmospheric pressure 1 kg of water uses approximately 1,7 m3; at 0,1 mbar of pressure this equals to 11.000 m3 (See table below).
So whenever very low pressures are needed, large vacuum pumps are needed or an ice condenser is inserted to reduce the installed vacuum capacity. Also the diameter of the piping (due to large vapor volume flows) might become limiting. Another normal feature is the limiting value of the heat exchange.

Values of 1 Kg of H2O      
Pressure Temperature [oC] Volume [m3] H2O / 1m3 [g]
1000 mbar 100 ± 1.7 588.2
100 mbar 46 ± 15 66.6
10 mbar 7 ± 130 7.7
1 mbar -20 ± 1100 0.9
0.1 mbar -42 ± 11,000 0.09

Much higher capacities

In the Active Freeze Dryer (only for ‘bulk’ applications) we have created such an enlarged heat exchange capacity, that this is - unlike the tray freeze dryers - normally not a limiting factor anymore. A direct consequence is that the Hosokawa Active Freeze Drying system will normally be looking at the highest possible pressure (still being restricted in any case to 6 mbar of course) and consequently will end up with much shorter drying times. For a 3 liter tray freeze drying system sublimation capacities can go up to 0,5 kg H2O/hour. In our Active Freeze Drying system this can be as high as 7 kg H2O /hour !

No handling / no contamination

As in our Active Freeze Drying system everything is produced within the system, again unlike the tray lyophilzators, the end product is directly produced as a fine powder. It therefore does not need further processing like milling or classifying.
As a consequence of this unique feature, there is not only a significantly reduced handling, but perhaps more importantly there is hardly any contamination possible !


An interesting feature coming automatically with the Active Freeze Drying method is the improvement of product quality. This can be anything, like PSD, color, taste, redisperseability, survival rate, yield etc.

Active Freeze Drying applications

The active freeze drying method has proven its value in a large number of applications we have carried out in our pilot plant. Nevertheless there are also a few limitations.
The active freeze drying method is not applicable for freeze drying materials in vials. A further limitation might be the presence of large contents of sugar(s). Here the reduction of the triple point and the eutectic point may cause problems. Please call Hosokawa Micron in case this aspect is of interest to you.

Pharmaceutical applications

This large market for all kinds of API’s, proteins, peptides, gelifient agent, lipids and bacterial cultures. There even lures a potential for Nano-material (actives) for pharmaceutical applications.

Classic tray freeze dryer particles Active freeze dryer particles

Food applications

Successful applications so far are found for the drying of extracts, milk derivatives, bacterial cultures, enzymes, yeast, and even soups.

For more information: Hosokawa Micron bv

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Hosokawa Micron
Specialist in POWDER PROCESSING TECHNOLOGY: Mixing - Drying -...