A lyophilizer, also known as a freeze dryer, works by freezing materials, reducing the pressure, and adding heat to allow frozen water in the materials to sublimate. The lyophilizer executes a water removal process to preserve perishable materials and extend shelf life by freezing the material and reducing pressure and temperature to allow frozen water to change directly from solid to vapor without passing through the liquid phase. Lyophilizers are used to dry heat-sensitive products, increase shelf life, and reduce weight for storage, shipping and transportation.

2. What is a lyophilizer? How does it work?
• Lyophilizer and freeze dryer are synonymous names for the same
equipment.
• A lyophilizer executes a water removal process typically used to
preserve perishable materials, to extend shelf life or make the material
more convenient for transport.
• Lyophilizers work by freezing the material, then reducing the
pressure and adding heat to allow the frozen water in the material to
sublimate.

3. Table of Contents
• 1.Principle
• 2.Construction of Freeze Dryer
• 3.Diagram of Freeze Dryer
• 4.Working of Freeze Dryer
• 5.Freeze Drying Steps
• 6.Advantage of Freeze Dryer
• 7.Disadvantage of Freeze Dryer
• 8.Applications of Freeze Dryer

4. 1.Principle
• The principle involved in freeze-drying is sublimation, where water
passes directly from solid-state (ice) to the vapour state without
passing through the liquid state.
• Sublimation of water can take place at pressures and temperatures
below the triple point of water.
• (The temperature and pressure at which a substance can exist in
equilibrium in the liquid, solid, and gaseous states. The triple point of
pure water is at 0.01°C and 4.58 mm Hg.)
• The material to be dried is first frozen and then subjected under a
high vacuum to heat (by conduction or radiation or by both) so that
frozen liquid sublimes leaving only non-volatile solid, dried
components of the original liquid.

5. 2.Construction of Freeze Dryer
• Generally, there are three types of freeze dryers, for example,
manifold freeze-dryer, rotary freeze dryer and tray-style freeze-dryer.
• These freeze-dryers differ in the method by which the dried
substance is interfaced with a condenser.
• The components common to all of them are a vacuum pump to
reduce the ambient gas pressure and a condenser to remove the
moisture by condensation on a surface cooled to -20 to -80 °C.
• A freeze dryer consists of a vacuum chamber wherein products to be
dried are kept on shelves and capable of cooling and heating
containers and their contents.
• A vacuum pump, a refrigeration unit, and associated controls are
connected to the vacuum chamber.

6. 3.Diagram of Freeze Dryer

7. 4.Working of Freeze Dryer
• Traditional freeze-drying is a complex process that requires a careful balancing of sample,
equipment and processing techniques.
• In this process, water is removed from a sample after it is frozen and placed under a vacuum,
allowing the ice to change directly from solid to vapor without passing through a liquid phase.
• It is performed at temperature and pressure conditions below the triple point of the liquid, to
enable sublimation of frozen material.
• The entire process is performed at low temperature and pressure. Steps involved in lyophilization
start from sample preparation followed by freezing, primary drying and secondary drying, to obtain
the final dried product.
• The vapour pressure of water increases with an increase in temperature during the primary
drying.
• Therefore, primary drying temperature should be kept as high as possible, but below the critical
process temperature, to avoid a loss of cake structure.
• There are four important stages in the complete freeze drying process namely pretreatment,
freezing, primary drying, and secondary drying.

8. 5.Freeze Drying Steps
Preparation and pretreatment
↓
Pre freezing for solidifying water
↓
Primary Drying
↓
Secondary Drying
↓
Packing

9. Pretreatment:
• It includes any method of treatment of the product before freezing.
This may include concentrating the product, the revision of the
formulation (ie, the addition of components to increase stability and/or
improve processing), decreasing a high vapor pressure solvent, or
increasing the surface area.
• Pretreatment methods include freezing concentration, solution-
phase concentration, formulation to preserve the appearance of the
product, formulation to stabilize reactive products, formulation to
increase the surface area, and decreasing high vapor pressure solvent.

10. Pre freezing:
• The product should be frozen at a temperature low enough to solidify completely. Since freeze-
drying is a change in the state from the solid phase to the gas phase, the material to be freeze-dried
must first be adequately pre-frozen.
• The pre-freezing method and the final temperature of the frozen product can affect the ability to
successfully freeze the material.
• The rapid cooling results in small ice crystals, useful for preserving structures that will be
examined microscopically, but it produces a product that is more difficult to lyophilize.
• Slower cooling results in large ice crystals and a less restrictive channel in the matrix during the
drying process. The products are frozen in two ways, most of the products that are lyophilized
consist mainly of water. Most of the samples to be lyophilized are eutectic, which are mixtures of
substances that freeze at a lower temperature than the surrounding water.
• It is very important in lyophilization to pre-freeze the product below the eutectic temperature
before beginning the lyophilization process.
• The second type of frozen product is a suspension that is subjected to the formation of glass
during the freezing process.

11. Primary drying:
• After pre-freezing the product, conditions must be established in which the ice
can be removed from the frozen product through sublimation, resulting in a dry,
structurally intact product.
• This requires very careful control of the two parameters: Temperature and
Pressure involved in the lyophilization system.
• The sublimation rate of a frozen product depends on the difference in vapor
pressure of the product compared to the vapor pressure of the ice collector.
• The molecules migrate from the high-pressure à lower pressure area. As the
vapor pressure is related to the temperature, the temperature of the product must
be warmer than the temperature of the cold trap (ice collector).
• The temperature at which a product is lyophilized is balanced between the
temperature that maintains the frozen integrity of the product and the temperature
that maximizes the vapor pressure of the product. This balance is key to optimum
drying.

12. Heat enters the products by one of several
mechanisms:
1.By direct contact between the container base and the shelf or
2.By conduction across the container base and then through the frozen
mass to the drying front or
3.By gaseous convection between the product and residual gas
molecules in the chamber or
4.By radiation.

13. Secondary Drying:
• After primary freeze-drying is complete, and all ice has sublimed,
bound moisture is still present in the product.
• The product appears dry, but the residual moisture content may be as
high as 7-8%. Continued drying is necessary at a warmer temperature
to reduce the residual moisture content to optimum values. This
process is called ‘Isothermal Desorption’.
• Secondary drying is usually carried out for approximately 1/3 or 1/2
of the time required for primary drying.

14. Packing:
• By replacing vacuum with inert gas, bottles and vials are closed.

15. 6.Advantage of Freeze Dryer
• This is suitable for drying heat sensitive products
• Freeze-dried product is porous and easy to be rehydrated and
instantly dissolved.
• Drying takes place at very low temperatures, so that enzyme action
is inhibited and chemical decomposition, particularly hydrolysis,
is minimized.
• Denaturation of protein does not occur.
• Loss of volatile material is less.
• Sterility can be maintained.

16. 7.Disadvantage of Freeze Dryer
• The process is very slow
• Expensive process.
• It is not a general method of drying, but it is limited to certain types
of valuable products that can not be dried by any other means.
• The period of drying is high
• The product is prone to oxidation, due to the high porosity and large
surface area. Therefore, the product must be vacuum packed or with
inert gas or in a container

17. 8.Applications of Freeze Dryer
• Freeze-drying is used to increase the shelf life of thermolabile products, such
as vaccines and other injectable.
• It is used to enhance stability of products during storage, shipping, and
transportation.
• Freeze-drying is used to reduce weight of products.
• It is used to preserve blood products in freeze-dried form.
• It is used in chemical synthesis to make products more stable and easier to
dissolve in water.
• Freeze-drying can effectively be used in bio-separations in purification
procedures.
• It can be used to concentrate low molecular weight substances that are too
small to be removed by a membrane filtration.