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Freeze Drying 101

Pharmaceutical and biotechnology

Pharmaceutical companies often use freeze-drying to increase the shelf life of the products, such as live virus vaccines, biologics and other injectables. By removing the water from the material and sealing the material in a glass 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. Freeze-dried pharmaceutical products are produced as lyophilized powders for reconstitution in vials and more recently in prefilled syringes for self-administration by a patient. Examples of lyophilized biological products include many vaccines such as Measles Virus Vaccine Live, Typhoid Vaccine, Meningococcal Polysaccharide Vaccine Groups A and C Combined. Other freeze-dried biological products include Antihemophilic Factor VIII, Interferon alfa, anti-blood clot medicine Streptokinase and Wasp Venom Allergenic Extract. Many biopharmaceutical products based on therapeutic proteins such as monoclonal antibodies require lyophilization for stability. Examples of lyophilized biopharmaceuticals include blockbuster drugs such as Etanercept (Enbrel by Amgen), Infliximab (Remicade by Janssen Biotech), Rituximab and Trastuzumab (Herceptin by Genentech). Freeze-drying is also used in manufacturing of raw materials for pharmaceutical products. Active Pharmaceutical Product Ingredients (APIs) are lyophilized to achieve chemical stability under room temperature storage. Bulk lyophilization of APIs is typically conducted using trays instead of glass vials. Dry powders of probiotics are often produced by bulk freeze-drying of live microorganisms such as Lactic acid bacteria and Bifidobacteria.

Food and agriculture-based industries

Although freeze-drying is used to preserve food, its earliest use in agriculturally based industries was in processing of crops such as peanuts/groundnuts and tobacco in the early 1970s. Because heat, commonly used in crop and food processing, invariably alters the structure and chemistry of the product, the main objective of freeze-drying is to avoid heat and thus preserve the structural and chemical integrity/composition with little or no alteration. Therefore, freeze-dried crops and foods are closest to the natural composition with respect to structure and chemistry. The process came to wide public attention when it was used to create 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 products are popular and convenient for hikers. More dried food can be carried per the same weight of wet food, and remains in good condition for longer than wet food, which tends to spoil quickly. Hikers 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 a popular snack choice, especially among toddlers, preschoolers, hikers and dieters, as well as being used by some pet owners as a treat for pet birds. Most commercial freezing is done either in cold air kept in motion by fans (blast freezing) or by placing the foodstuffs in packages or metal trays on refrigerated surfaces (contact freezing). Culinary herbs, vegetables (such as vitamin-rich spinach and watercress), the temperature sensitive baker`s yeast suspension and the nutrient-rich pre-boiled rice can also be freeze-dried. During three hours of drying the spinach and watercress has lost over 98% of its water content, followed by the yeast suspension with 96% and the pre-boiled rice by 75%. The air-dried herbs are far more common and less expensive. Freeze dried tofu is a popular foodstuff in Japan (“Koya-dofu” or “shimi-dofu” in Japanese).

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. In nanotechnology, freeze-drying is used for nanotube purification to avoid aggregation due to capillary forces during regular thermal vaporization drying.

Other Uses

Organizations such as the Document Conservation Laboratory at the United States National Archives and Records Administration (NARA) 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. 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.


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