Principle, Construction, Working, Uses, Merits and Demerits of Freeze Dryer : Pharmaceutical Guidelines -->

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Principle, Construction, Working, Uses, Merits and Demerits of Freeze Dryer

The process of lyophilization involves a phenomenon known as sublimation.

Freeze Dryer


The process of lyophilization involves a phenomenon known as sublimation. An object that is liquid passes directly from one state to another, unlike an object that is solid (ice). It involves removing the water from the frozen state material and then heating it (by conduction or radiation or even both) to the point that the evaporated liquid leaves only the solids or dry components of the original liquid. It is necessary to dry materials at lower temperatures and pressures than the triple point.


There are three types of freeze dryers. The tray-style freeze-dryer, the rotary freeze-dryer, and the manifold freeze-dryer are the three types of freeze-dryers. Each of these methods relies on a vacuum pump to lower the atmosphere pressure in a vessel that holds the substance to be dried and a condenser to remove moisture through condensation on a surface that is chilled to between 20 and 80°C. Freeze-dried substances are connected to condensers in three different ways: manifold, rotary, and tray.
  • An insulated tube connected by a circular bend connects multiple containers filled with dried goods to a condenser.
  • Within rotary freeze-dryers are large reservoirs used to store drying substances. Pellets, cubes and other liquids are usually dried with rotary freeze-dryers. The cylindrical reservoir of a rotary dryer rotates during drying so that the substance is evenly dried.
  • For storing dried materials, a tray freeze-dryer includes a large reservoir. A rectangular reservoir with shelves and trays is usually used to store pharmaceutical solutions and tissue extracts, which are collected in the reservoir.
In a freeze dryer, products are kept in a vacuum chamber that cools and heats the containers and contents as they are dried. Vacuum chambers are connected to vacuum pumps, refrigeration units, and electronic controls.


The process of freeze drying is complex and requires an optimal balance between equipment, product, and processing technique. After a product has been frozen, water is removed from it and the product is put under a vacuum, causing the ice to turn directly into vapour without passing through a liquid phase. Under these conditions, frozen material can be sublimated at temperatures below the triple point of liquid. Temperatures and pressure remain low throughout. A lyophilized product is obtained after the sample is prepared, frozen, dried, and then secondary dried. During lyophilization, water is removed from the sample through a concentration gradient of water vapour. Water vapour pressure increases as temperature rises during the primary drying process. Keeping the primary drying temperature above the critical temperature will prevent the loss of cake structure.

Freeze-drying consists of four important steps: pretreatment, freezing, primary drying, and secondary drying.

Pretreatment - This stage is for determining the freezing point of the product, solution-phase concentration, preserving product appearance, stabilizing reactive products, reducing the concentration of high-vapor pressure solvents, and increasing surface area before freezing. Sometimes, pre-treating a product is dictated by cycles time or product quality considerations rather than the knowledge of freeze-drying and its requirements.

Freezing - The liquid sample is cooled down to between 40° C and 60 °C in the freezing stage until parts of it crystallize into pure ice, and the remainder is freeze-concentrated into a glassy state when the viscosity is too high to permit further crystallization.

Primary drying - A primary dry process removes the ice formed by freezing by sublimating it under vacuum at low temperatures. The resulting amorphous solute, typically 10% water, has a very porous structure that is highly porous. A pressure of 10 - 4 to 10 - 5 atmospheres is used, and a temperature of –45 to –20°C is used in this step. Heat and mass are transferred during the sublimation process during primary drying.

Secondary drying - As the sample is gradually heated between 10 °C and 15 °C while maintaining low pressure, most of the remaining water is desorbed from the glass. A good cake should be dry, reconstituted easily, and have a low amount of moisture (below 5% weight to weight).


  • Vaccines and other injectables are often freeze-dried by pharmaceutical companies in order to increase their shelf life.
  • Material can be stored, shipped, and later reconstituted into its original form by removing the water and sealing the material in a vial under vacuum.
  • By freeze-drying biologicals, it is possible to preserve them and make them lightweight.
  • The freeze-dried form of blood products is used for preservation.
  • Often, freeze-dried products are used in chemical synthesis to stabilize them or make them more soluble in water.
  • By freeze-drying, solvents can be effectively removed that can be used in the final steps of bio-separation.
  • Furthermore, low molecular weight substances that are too small to be removed by a filtration membrane can be concentrated using this technique.


  • Vacuum conditions provide good protection for oxidizable substances.
  • A long drying time is attributed to water removal of 95%-99.5%.
  • There is uniformity in the content of loaded quantities.
  • Aseptic process resulted in little contamination.
  • Volatile chemicals and nutrient- and fragrance-sensitive components are minimized.
  • Due to the fact that growth of bacteria and enzymes cannot occur at low temperatures, there are very few changes in the properties.
  • Under normal temperatures, thermostable products can be transported and stored.
  • Reconstitution is done rapidly, usually within 10 seconds.
  • The dried material maintains a homogeneous distribution of constituents.
  • It is possible to achieve and maintain product stability.


  • It may be necessary to use a high vacuum to remove volatile compounds.
  • Operation with the highest unit cost.
  • The ability of an individual drug to cope with low temperatures is one of its primary drawbacks.
  • Aseptic loading of vials into the dryer chamber and sterilization and sterility assurance of the chamber raises some concerns.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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