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Freeze Drying is also known as Lyophilization or cryo-dessication. It is a process for removing water from the substance by the process of dehydration under vacuum while substance is in frozen state.

Lyophilization technology is used to freeze-dry products, such as biologicals, bacterial cultures, analytical chemistry moieties, and therapeutic molecules (e.g., antibodies, vaccines, drugs, and heat-sensitive proteins).

Freeze drying is carried out using a process called sublimation, i.e., transition of a substance from solid to vapor state, without passing through intermediate liquid phase.

Lyophilization imparts higher stability, broader temperature tolerance, and longer shelf life to most pharmaceutical formulations that are unstable in aqueous solution.

It was first developed as a commercial process in 1930s.

This course covers basic principles, steps and applications of freeze drying.

Figure 1. Porthole of a lyophilization tank used by the pharmaceutical industry
Figure 1. Porthole of a lyophilization tank used by the pharmaceutical industry


Principal steps involved in a typical lyophilization process include pretreatment, freezing, primary and secondary drying.

Lyophilization equipment consists of a drying chamber, condensers (water and drying), a cooling system, and a vacuum system.

Determination of stability of lyophilized samples is done either by accelerated or real-time stability studies.


It can be done by adding additives that stabilize the product, bulking agents that add mass to the product, or filtration to reduce volume and concentrate the product.

Pretreatment determines the quality of the lyophilization.


The principle function of the freezing process is to separate the solvent from the solutes. For an aqueous system, water forms ice crystal, and solute gets confined to the interstitial region between the ice crystal.

The temperature necessary to achieve complete freezing of the formulation (system containing solvent, which provides stability upon its removal) depends upon the nature of solvent and other components of formulation.

There are two types of freezing,

    • ¬†fast freezing¬†
    • slow freezing


Once the sample reaches complete frozen state, the pressure is reduced and heat is applied to initiate sublimation of ice crystals.

Primary drying process gets completed when all ice crystals are removed from the sample. 90% of water is removed by primary drying process and the remaining 10% bound water is removed during secondary drying step.

Controlled drying and heating rates during the primary drying phase are key steps to lyophilization success.

Figure 2.  Lyophilization Process used for Probiotic Bacteria
Figure 2. Lyophilization Process used for Probiotic Bacteria

Factors that affect the efficiency of lyophilization are sample size, surface area of the sample, thickness of the sample, eutectic temperature, solute concentration, type of instrument and vaccum, and temperature of condensor.

Eutectic temperature is the most important factor determining how much sample can be lyophilized at one time.

Principal advantages of lyophilization process over conventional drying methods are,

  • preservation of chemical and biological potency
  • protection of sample from solution effects and chemical degradation
  • homogeneity in final product
  • ease of dispensing
  • accurate and sterile dosing into final product containers.

Disadvantages associated with this process are high cost of equipment, high-energy costs, and long processing time.

Application of Freeze Drying

Lyophilization has several applications in various industries.

  • In pharmaceutical industry, It is a preferred method for the preservation of vaccines, pharmaceuticals, and other proteins. Lyophilization products comprise 10% of total cost ($8 billion) in pharmaceutical industry.
  • In veterinary science, most common use of lyophilization range from production of vaccine for pets to inoculation of herds of cattle or flocks of poultry. This technique is used protect animals as well improve their quality.
  • In food industry, various food products such as beef, ice cream, additives, and astronaut food are packed by lyophilization.
  • Other applications of lyophilization include conservation of special bacterial and animal strains.