Freeze-drying, also known as lyophilisation, lyophilization, or cryodesiccation, is a dehydration
process typically used to preserve a perishable material or make the material more convenient
for transport. Freeze-drying works by freezing the material and then reducing the surrounding
pressure to allow the frozen water in the material to sublimate directly from the solid
phase to the gas phase.
The origins of freeze drying The Andean civilizations preserved potatoes
using a freeze drying process. They called this foodstuff chuño.
Freeze-drying was actively developed during WWII. Serum being sent to Europe from the
US for medical treatment of the wounded required refrigeration, but because of the lack of
simultaneous refrigeration and transport, many serum supplies were spoiling before reaching
their intended recipients. The freeze-drying process was developed as a commercial technique
that enabled serum to be rendered chemically stable and viable without having to be refrigerated.
Shortly thereafter, the freeze-dry process was applied to penicillin and bone, and lyophilization
became recognized as an important technique for preservation of biologicals. Since that
time, freeze-drying has been used as a preservation or processing technique for a wide variety
of products. These applications include the following but are not limited to: the processing
of food, pharmaceuticals, and diagnostic kits; the restoration of water damaged documents;
the preparation of river-bottom sludge for hydrocarbon analysis; the manufacturing of
ceramics used in the semiconductor industry; the production of synthetic skin; the manufacture
of the sulphur coated vials; the restoration of historic/reclaimed boat hulls.
The freeze-drying stages There are four stages in the complete drying
process: pretreatment, freezing, primary drying, and secondary drying.
Pretreatment Pretreatment includes any method of treating
the product prior to freezing. This may include concentrating the product, formulation revision,
decreasing a high vapor pressure solvent or increasing the surface area. In many instances
the decision to pretreat a product is based on theoretical knowledge of freeze-drying
and its requirements, or is demanded by cycle time or product quality considerations. Methods
of pretreatment include: freeze concentration, solution phase concentration, formulation
to preserve product appearance, formulation to stabilize reactive products, formulation
to increase the surface area, and decreasing high vapor pressure solvents.
Freezing In a lab, this is often done by placing the
material in a freeze-drying flask and rotating the flask in a bath, called a shell freezer,
which is cooled by mechanical refrigeration, dry ice and methanol, or liquid nitrogen.
On a larger scale, freezing is usually done using a freeze-drying machine. In this step,
it is important to cool the material below its triple point, the lowest temperature at
which the solid and liquid phases of the material can coexist. This ensures that sublimation
rather than melting will occur in the following steps. Larger crystals are easier to freeze-dry.
To produce larger crystals, the product should be frozen slowly or can be cycled up and down
in temperature. This cycling process is called annealing. However, in the case of food, or
objects with formerly-living cells, large ice crystals will break the cell walls, resulting
in the destruction of more cells, which can result in increasingly poor texture and nutritive
content. In this case, the freezing is done rapidly, in order to lower the material to
below its eutectic point quickly, thus avoiding the formation of ice crystals. Usually, the
freezing temperatures are between −50 °C and −80 °C. The freezing phase is the most
critical in the whole freeze-drying process, because the product can be spoiled if improperly
done. Amorphous materials do not have a eutectic
point, but they do have a critical point, below which the product must be maintained
to prevent melt-back or collapse during primary and secondary drying.
Primary drying During the primary drying phase, the pressure
is lowered, and enough heat is supplied to the material for the water to sublime. The
amount of heat necessary can be calculated using the sublimating molecules’ latent
heat of sublimation. In this initial drying phase, about 95% of the water in the material
is sublimated. This phase may be slow, because, if too much heat is added, the material’s
structure could be altered. In this phase, pressure is controlled through
the application of partial vacuum. The vacuum speeds up the sublimation, making it useful
as a deliberate drying process. Furthermore, a cold condenser chamber and/or condenser
plates provide a surface(s) for the water vapour to re-solidify on. This condenser plays
no role in keeping the material frozen; rather, it prevents water vapor from reaching the
vacuum pump, which could degrade the pump's performance. Condenser temperatures are typically
below −50 °C. It is important to note that, in this range
of pressure, the heat is brought mainly by conduction or radiation; the convection effect
is negligible, due to the low air density. Secondary drying
The secondary drying phase aims to remove unfrozen water molecules, since the ice was
removed in the primary drying phase. This part of the freeze-drying process is governed
by the material’s adsorption isotherms. In this phase, the temperature is raised higher
than in the primary drying phase, and can even be above 0 °C, to break any physico-chemical
interactions that have formed between the water molecules and the frozen material. Usually
the pressure is also lowered in this stage to encourage desorption. However, there are
products that benefit from increased pressure as well.
After the freeze-drying process is complete, the vacuum is usually broken with an inert
gas, such as nitrogen, before the material is sealed.
At the end of the operation, the final residual water content in the product is extremely
low, around 1% to 4%. Properties of freeze-dried products
If a freeze-dried substance is sealed to prevent the reabsorption of moisture, the substance
may be stored at room temperature without refrigeration, and be protected against spoilage
for many years. Preservation is possible because the greatly reduced water content inhibits
the action of microorganisms and enzymes that would normally spoil or degrade the substance.
Freeze-drying also causes less damage to the substance than other dehydration methods using
higher temperatures. Freeze-drying does not usually cause shrinkage or toughening of the
material being dried. In addition, flavours, smells and nutritional content generally remain
unchanged, making the process popular for preserving food. However, water is not the
only chemical capable of sublimation, and the loss of other volatile compounds such
as acetic acid and alcohols can yield undesirable results.
Freeze-dried products can be rehydrated much more quickly and easily because the process
leaves microscopic pores. The pores are created by the ice crystals that sublimate, leaving
gaps or pores in their place. This is especially important when it comes to pharmaceutical
uses. Freeze-drying can also be used to increase the shelf life of some pharmaceuticals for
many years. Freeze-drying protectants
Similar to cryoprotectants, some molecules protect freeze-dried material. Known as lyoprotectants,
these molecules are typically polyhydroxy compounds such as sugars, polyalcohols, and
their derivatives. Trehalose and sucrose are natural lyoprotectants. Trehalose is produced
by a variety of plant, fungi, and invertebrate animals that remain in a state of suspended
animation during periods of drought. Applications of freeze-drying
Pharmaceutical and biotechnology Pharmaceutical companies often use freeze-drying
to increase the shelf life of the products, such as vaccines and other injectables. By
removing the water from the material and sealing the material in a vial, the material can be
easily stored, shipped, and later reconstituted to its original form for injection. Another
example from the pharmaceutical industry is the use of freeze drying to produce tablets
or wafers, the advantage of which is less excipient as well as a rapidly absorbed and
easily administered dosage form. Food and Agro industry
Although Freeze-drying is used to preserve food, the resulting product being very lightweight,its
early use was initiated processing of crops such as peanuts/groundnuts and tobacco in
the early 1970s . Simply explained, freeze drying means the material is continuously
in a frozen state while the moisture is being removed through negative pressure in the chamber
where the frozen materials are located. Because the removed moisture may damage the vacuum
pump, the removed moisture/vapor must be refrozen to the surface of a condenser, which is then
brought to room temperature to drain the moisture out. The process has been popularized in the
forms of freeze-dried ice cream, an example of astronaut food. It is also widely used
to produce essences or flavourings to add to food. Because of its light weight per volume
of reconstituted food, freeze dried product is also popular and convenient for hikers.
More dried food can be carried per the same weight of wet food, and has the benefit of
"long life" compared to wet food that tends to spoil quickly. The hikers then reconstitute
the food with water available at point of use. Instant coffee is sometimes freeze-dried,
despite the high costs of the freeze-driers used. The coffee is often dried by vaporization
in a hot air flow, or by projection onto hot metallic plates. Freeze-dried fruits are used
in some breakfast cereal or sold as a snack, and are an especially popular snack choice
among toddlers, preschoolers and dieters, as well as being used by some pet owners as
a treat for pet birds. Culinary herbs are also freeze-dried, although air-dried herbs
are far more common and less expensive. Freeze dried tofu is a popular foodstuff in Japan.
Technological industry In chemical synthesis, products are often
freeze-dried to make them more stable, or easier to dissolve in water for subsequent
use. In bioseparations, freeze-drying can be used
also as a late-stage purification procedure, because it can effectively remove solvents.
Furthermore, it is capable of concentrating substances with low molecular weights that
are too small to be removed by a filtration membrane.
Freeze-drying is a relatively expensive process. The equipment is about three times as expensive
as the equipment used for other separation processes, and the high energy demands lead
to high energy costs. Furthermore, freeze-drying also has a long process time, because the
addition of too much heat to the material can cause melting or structural deformations.
Therefore, freeze-drying is often reserved for materials that are heat-sensitive, such
as proteins, enzymes, microorganisms, and blood plasma. The low operating temperature
of the process leads to minimal damage of these heat-sensitive products
Other uses Organizations such as the Document Conservation
Laboratory at the United States National Archives and Records Administration have done studies
on freeze-drying as a recovery method of water-damaged books and documents. While recovery is possible,
restoration quality depends on the material of the documents. If a document is made of
a variety of materials, which have different absorption properties, expansion will occur
at a non-uniform rate, which could lead to deformations. Water can also cause mold to
grow or make inks bleed. In these cases, freeze-drying may not be an effective restoration method.
In bacteriology freeze-drying is used to conserve special strains.
In high-altitude environments, the low temperatures and pressures can sometimes produce natural
mummies by a process of freeze-drying. Advanced ceramics processes sometimes use
freeze-drying to create a formable powder from a sprayed slurry mist. Freeze-drying
creates softer particles with a more homogeneous chemical composition than traditional hot
spray drying, but it is also more expensive. Freeze drying is also used for floral preservation.
Wedding bouquet preservation has become very popular with brides who want to preserve their
wedding day flowers A new form of burial which previously freeze-dries
the body with liquid nitrogen has been developed by the Swedish company Promessa Organic AB,
which puts it forward as an environmentally friendly alternative to traditional casket
and cremation burials. Freeze-drying equipment
There are essentially three categories of freeze-dryers: the manifold freeze-dryer,
the rotary freeze-dryer and the tray style freeze-dryer. Two components are common to
all types of freeze-dryers: a vacuum pump to reduce the ambient gas pressure in a vessel
containing the substance to be dried and a condenser to remove the moisture by condensation
on a surface cooled to −40 to −80 °C. The manifold, rotary and tray type freeze-dryers
differ in the method by which the dried substance is interfaced with a condenser. In manifold
freeze-dryers a short usually circular tube is used to connect multiple containers with
the dried product to a condenser. The rotary and tray freeze-dryers have a single large
reservoir for the dried substance. Rotary freeze-dryers are usually used for
drying pellets, cubes and other pourable substances. The rotary dryers have a cylindrical reservoir
that is rotated during drying to achieve a more uniform drying throughout the substance.
Tray style freeze-dryers usually have rectangular reservoir with shelves on which products,
such as pharmaceutical solutions and tissue extracts, can be placed in trays, vials and
other containers. Manifold freeze-dryers are usually used in
a laboratory setting when drying liquid substances in small containers and when the product will
be used in a short period of time. A manifold dryer will dry the product to less than 5%
moisture content. Without heat, only primary drying can be achieved. A heater must be added
for secondary drying, which will remove the bound water and will produce a lower moisture
content. Tray style freeze-dryers are typically larger
than the manifold dryers and are more sophisticated. Tray style freeze-dryers are used to dry a
variety of materials. A tray freeze-dryer is used to produce the driest product for
long-term storage. A tray freeze-dryer allows the product to be frozen in place and performs
both primary and secondary freeze-drying, thus producing the driest possible end-product.
Tray freeze-dryers can dry products in bulk or in vials or other containers. When drying
in vials, the freeze-dryer is supplied with a stoppering mechanism that allows a stopper
to be pressed into place, sealing the vial before it is exposed to the atmosphere. This
is used for long-term storage, such as vaccines. Improved freeze drying techniques are being
developed to extend the range of products that can be freeze dried, to improve the quality
of the product, and to produce the product faster with less labor.
See also Food preservation
Freeze-dried Food and NASA List of dried foods
Supercritical drying References
Notes Harris, E. L. V. and S. Angal. Protein Purification
Methods. Oxford University Press. ISBN 0-19-963003-8 Kennedy, John F. and Joaquim M. S. Cabral.
Recovery Processes for Biological Materials. John Wiley & Sons Ltd.
Efficacy of Various Drying Methods Loi, P., Iuso, D., Czernik, M., Zacchini,
F., & Ptak, G. Towards storage of cells and gametes in dry form. Trends in biotechnology,
31(12), 688-695. doi: 10.1016/j.tibtech.2013.09.004