Lyophilization: A Primer

Optimized freeze-drying cycles can offer scientific and business advantages.
May 02, 2013

Freeze drying, or lyophilization, is a stabilization method that is widely used in the pharmaceutical industry for drugs, vaccines, antibodies, and other biological material. Because the product is dried without excessive heating, proteins and other products that would be thermally denatured can be successfully preserved without loss of activity.


TAKESHI NISHIJIMA/MARIA TOUTOUDAKI/GETTY IMAGES; DAN WARD
Freeze-dried products have a very high surface area, which enables them to be reconstituted quickly. This quick reconstitution is particularly important in the case of emergency vaccines and antibodies, which need to be administered as soon as possible.

Every formulation has different freeze-drying characteristics and, therefore, different processing requirements. To ensure cycles are both robust and efficient, they should be tailor-made for each formulation. Failure to do so can lead to inconsistent dryness across samples, reduced stability during storage, and reduced activity on rehydration.

There are three main business advantages of optimizing a product's lyophilization cycle:
  • Financial gain: optimal lyophilization cycles use only the energy and time required, shortening process time and increasing product throughput.
  • Product excellence: a well-dried product exhibits a long shelf life and maximum activity on rehydration.
  • Quality and regulatory assurance: consistency throughout batches is assured and regulatory submissions are completed with the inclusion of lyophilization cycle data.

The freeze-drying cycle


Figure 1: During freeze drying the temperature and pressure are controlled so that the frozen solvent moves directly from the solid to the gas phase without passing through the liquid phase.
Lyophilization is a complex drying process that involves removing the solvent from a material by sublimation. Sublimation is achieved through varying the temperature and pressure of the material so that the solvent does not pass through the liquid stage, but moves directly from the solid phase to the gas phase (see Figure 1). Lyophilization takes place in three main stages: freezing, primary drying, and secondary drying. Each stage has its own challenges.