Lyophilization is a stabilizing process in which a substance is first frozen and then the quantity of the solvent (generally water) is reduced, first by sublimation (referred to as the primary drying process) and then desorption (known as the secondary drying process) to values that will no longer support biological activity or chemical reactions.
Lyophilization can also be described as a method of drying substances such as proteins, microorganisms or pharmaceutical preparations without destroying their physical structure. This is achieved by freezing a material to a temperature below its eutectic or glass transition point, creating a deep vacuum, adding the latent heat of sublimation then re-freezing the resulting vapor on a condenser. Precise control of heat input permits drying from a frozen state without product melt-back.
Lyophilization’s 3 Primary Stages
Lyophilization occurs in three phases, with the first and most critical being the freezing phase. Proper lyophilization can reduce drying times by 30%.
There are various methods to freezing the product. Freezing can be done in a freezer, a chilled bath (shell freezer) or on a shelf in the freeze dryer. Cooling the material below its triple point ensures that sublimation, rather than melting, will occur. This preserves its physical form.
Lyophilization is easiest to accomplish using large ice crystals, which can be produced by slow freezing or annealing. However, with biological materials, when crystals are too large they may break the cell walls, and that leads to less-than-ideal freeze drying results. To prevent this, the freezing is done rapidly. For materials that tend to precipitate, annealing can be used. This process involves fast freezing, then raising the product temperature to allow the crystals to grow.
Primary Drying (Sublimation) Phase
Lyophilization’s second phase is primary drying (sublimation), in which the pressure is lowered and heat is added to the material in order for the water to sublimate. The vacuum speeds sublimation. The cold condenser provides a surface for the water vapor to adhere and solidify. The condenser also protects the vacuum pump from the water vapor. About 95% of the water in the material is removed in this phase. Primary drying can be a slow process. Too much heat can alter the structure of the material.
Secondary Drying (Adsorption) Phase
Lyophilization’s final phase is secondary drying (adsorption), during which the ionically-bound water molecules are removed. By raising the temperature higher than in the primary drying phase, the bonds are broken between the material and the water molecules. Freeze dried materials retain a porous structure. After the lyophilization process is complete, the vacuum can be broken with an inert gas before the material is sealed. Most materials can be dried to 1-5% residual moisture.
Advantages of the Lyophilization
Lyophilization has many advantages over the other drying and preserving techniques.
- It maintains food/ biochemical and chemical reagent quality because they remains at a temperature that is below the freezing-point during the process of sublimation.The use of lyophilization is particularly important when processing lactic bacteria, because these products are easily affected by heat.
- Food/biochemicals and chemical reagents which are lyophilized can usually be stored without refrigeration, which results in a significant reduction of storage and transportation costs.
- Lyophilization greatly reduces weight, and this makes the products easier to transport. For example, many foods contain as much as 90% water. These foods are 10 times lighter after lyophilization.
- Because they are porous, most freeze-dried products can be easily rehydrated. Lyophilization does not significantly reduce volume, therefore water quickly regains its place in the molecular structure of the food/ biochemicals and chemical reagents.