Freeze drying


Freeze drying, also known as lyophilization or cryodesiccation, is a low temperature dehydration process that involves freezing the product and lowering pressure, thereby removing the ice by sublimation. This is in contrast to dehydration by most conventional methods that evaporate water using heat.
Because of the low temperature used in processing, the rehydrated product retains many of its original qualities. When solid objects like strawberries are freeze dried the original shape of the product is maintained. If the product to be dried is a liquid, as often seen in pharmaceutical applications, the properties of the final product are optimized by the combination of excipients. Primary applications of freeze drying include biological, biomedical, food processing, and preservation.

History

The Inca were freeze drying potatoes into chuño since the 13th century. The process involved multiple cycles of exposing potatoes to below freezing temperatures on mountain peaks in the Andes during the evening, and squeezing water out and drying them in the sunlight during the day. The Inca people also used the unique climate of the Altiplano to freeze dry meat.
The Japanese koya-dofu, freeze-dried tofu, dates to the mid-1500s in Nagano and the 1600s on Mount Koya.
Modern freeze drying began as early as 1890 by Richard Altmann who devised a method to freeze dry tissues, but went virtually unnoticed until the 1930s. In 1909, L. F. Shackell independently created the vacuum chamber by using an electrical pump. No further freeze drying information was documented until Tival in 1927 and Elser in 1934 had patented freeze drying systems with improvements to freezing and condenser steps.
A significant turning point for freeze drying occurred during World War II when blood plasma and penicillin were needed to treat the wounded in the field. Because of the lack of refrigerated transport, many serum supplies spoiled before reaching their recipients. The freeze-drying process was developed as a commercial technique that enabled blood plasma and penicillin to be rendered chemically stable and viable without refrigeration. In the 1950s–1960s, freeze drying began to be viewed as a multi-purpose tool for both pharmaceuticals and food processing.
In 2020, freeze dried candy saw a major surge in popularity due to viral popularity on social media with freeze dried versions of popular candies such as Skittles, Nerd Gummy Clusters, and SweeTarts appearing in stores.

Early uses in food

Freeze-dried foods became a major component of astronaut and military rations. What began for astronaut crews as tubed meals and freeze-dried snacks that were difficult to rehydrate, were transformed into hot meals in space by improving the process of rehydrating freeze-dried meals with water. As technology and food processing improved, NASA looked for ways to provide a complete nutrient profile while reducing crumbs, disease-producing bacteria, and toxins. The complete nutrient profile was improved with the addition of an algae-based vegetable-like oil to add polyunsaturated fatty acids. Polyunsaturated fatty acids are beneficial in mental and vision development and, as they remain stable during space travel, can provide astronauts with added benefits. The crumb problem was solved with the addition of a gelatin coating on the foods to lock in and prevent crumbs. Disease-producing bacteria and toxins were reduced by quality control and the development of the Hazard Analysis and Critical Control Points plan, which is widely used today to evaluate food material before, during, and after processing. With the combination of these three innovations, NASA could provide safe and wholesome foods to their crews from freeze-dried meals.
Military rations have also come a long way, from being served cured pork and corn meal to beefsteaks with mushroom gravy. How rations are chosen and developed is based on acceptance, nutrition, wholesomeness, producibility, cost, and sanitation. Additional requirements for rations include having a minimum shelf life of three years, being deliverable by air, being consumable in worldwide environments, and providing a complete nutritional profile. The new T-rations have been improved upon by increasing acceptable items and provide high quality meals while in the field. Freeze-dried coffee was also incorporated by replacing spray-dried coffee in the meal, ready-to-eat category.

Stages

There are four stages in the complete freeze 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. Food pieces are often IQF treated to make them free flowing prior to freeze drying. Freeze dried pharmaceutical products are in most cases parenterals administered after reconstitution by injection which need to be sterile as well as free of impurity particles. Pre-treatment in these cases consists of solution preparation followed by a multi-step filtration. Afterwards the liquid is filled under sterile conditions into the final containers which in production scale freeze dryers are loaded automatically to the shelves.
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.

Freezing and annealing

During the freezing stage, the material is cooled below its triple point, the temperature at which the solid, liquid, and gas phases of the material can coexist. This ensures that sublimation rather than melting will occur in the following steps. To facilitate faster and more efficient freeze drying, larger ice crystals are preferable. The large ice crystals form a network within the product which promotes faster removal of water vapor during sublimation. To produce larger crystals, the product should be frozen slowly or can be cycled up and down in temperature in a process called annealing. The freezing phase is the most critical in the whole freeze-drying process, as the freezing method can impact the speed of reconstitution, duration of freeze-drying cycle, product stability, and appropriate crystallization.
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.

Structurally sensitive goods

In the case of goods where preservation of structure is required, like food or objects with formerly-living cells, large ice crystals break the cell walls, resulting in increasingly poor texture and loss of nutrients. In this case, rapidly freezing the material to below its eutectic point avoids the formation of large ice crystals. Usually, the freezing temperatures are between and.

Primary drying

During the primary drying phase, the pressure is lowered, and enough heat is supplied to the material for the ice to sublimate. 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 for the water vapor to re-liquify and solidify on.
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, 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 1–4%.

Applications

Freeze-drying causes less damage to the substance than other dehydration methods using higher temperatures. Nutrient factors that are sensitive to heat are lost less in the process as compared to the processes incorporating heat treatment for drying purposes. Freeze-drying does not usually cause shrinkage or toughening of the material being dried. In addition, flavors, 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.

Pharmaceuticals and biotechnology

Pharmaceutical companies use freeze-drying to increase the shelf life of some 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 person.
Examples of lyophilized pharmaceutical drugs include: