• Pre-treatment – where components are added to the material to be freeze dried. This is done mainly to increase the yield, quality and appearance of the final product, but also to increase the temperature of drying and reduce cycle time, if possible.

• Freezing – the size of the ice crystals has a significant effect on the quality of the final freeze dried product. Large crystals dry faster, but in forming larger structures, biological material can be destroyed.

• Primary drying – during this step, the pressure inside the drying chamber is lowered and a very small amount of heat is applied. This step can take days in an industrial drying cycle, however, if too much heat is applied the structure could be altered or destroyed.

• Secondary drying – is the final attempt to remove remaining water molecules, since all the ice should have been removed in the primary phase. Pressure is usually further reduced and the temperature increased.

Uses in the Pharmaceutical Industry

Lyophilization has been used in many different research projects in the pharmaceutical industry. As has been mentioned, the process provides excellent retention of the three-dimensional structures of biological samples, which aids in the accuracy of drug developmental research.

Allowing the drying of heat-sensitive drugs and biologicals at low temperature, it is mainly used to improve the stability and storage of labile drugs. Commonly applied to the production of injectable dosage forms of drugs, pharmaceutical freeze-drying is also used to produce diagnostics. Less commonly, it is used to produce solid oral dosage forms that require a very fast dissolution rate.

By removing water/solvent and sealing the product in a vial, the shelf-life of injectables and vaccines can be increased. Therefore, pharmaceutical companies can easily store, ship, and later reconstitute the material to its original form for injection.

Lyophilization can also be used as a purification process in the later stages of sample preparation, due to how effective this process is in removing solvent from a product.

The technique does have some limitations though, and not all research techniques can benefit from samples prepared in this way. For example, X-ray crystallographic studies require a pure crystal, and samples that have been freeze-dried (the sample must be dialyzed to remove buffers and salts that are still present that may cause undesirable effects on the crystal) are not suitable for this. Even though some proteins such as catalase are known to crystallize after lyophilization, the process is generally not suited to crystallographic studies. However, lyophilization remains one of the most reliable and widely used techniques for sample preparation in the pharmaceutical industry.

The Future for Lyophilization

Lyophilization is an incredibly practical solution for the issues that research, production and storage which the pharmaceutical industry faces. Like any technique, however, it is not without its problems, which means that the process is always being refined. It remains one of the best-placed drying methods that is used in the pharmaceutical industry, and will do so for many years to come.