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B. Tech.

Seminar (CHE)

A Seminar Report
On

Title: FREEZE DRYING


Name: Sanjana Bhattacharyya
Roll Number: 115537
Copy for: Department

Date of submission: 5.02.2014

Department of Chemical Engineering


Heritage Institute of Technology, Kolkata

A Seminar Report
On

Title: FREEZE DRYING


Name: Sanjana Bhattacharyya
Roll Number: 115537
Copy for: Department

Date of submission: 5.02.2014

Department of Chemical Engineering


Heritage Institute of Technology, Kolkata

Abstract

This report provides an overview of freeze drying (lyophilization) with particular relevance to
pharmaceutical and food and industrial applications. The report discusses the phenomenon
that is the foundation of freeze drying method and the specifics of the process involved. The
comparison of both preservation processes, hot air and freeze-drying, was done taking into
account several important characteristics such as shrinkage, glass transition temperature,
processquality interaction, drying kinetics, costs and new improvements. An updated
bibliographic research served to compare both drying processes. Experimental data as well as
theoretical results, from several years of research in the subject, were presented and compiled
in order to support conclusions. Furthermore, the possible improvements have been stated as
well.
Keywords: freeze drying, lyophilization, freezing, food industry, pharmaceutical

Contents

1. Introduction

1.1 History

2. Basic principle

3. Freeze drying process

3.1 Pre-treatment

3.2 Freezing

3.3 Primary drying

3.4 Secondary drying

4. Freeze dryer

4.1 Rotary freeze dryer

10

4.2 Manifold freeze dryer

10

4.3 Tray style freeze dryer

10

5. Applications

11

5.1 Food industry

11

5.2 Pharmaceutical industry

14

5.3 Technological industry

15

5.4 Other applications

15

6. Possible improvements

16

7. Conclusion

17

List of figures

1. Phase diagram of water

2. Lyophilization cycle

3. Comparison of minimum chamber pressure as a function of drying rate

4. A freeze dried fruit platter retains flavor and texture well

12

5. Freeze dried and dehydrated fruits differ visibly in terms of texture and colour

14

6. Scanning Electron Microscopy (SEM) analysis of freeze dried


pharmaceutical product

15

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1. Introduction
Freeze drying, or lyophilization as it is referred to in the Pharmaceutical and Diagnostic
Industries, is a dehydration technique, which enables liquid or slurry products, which have
previously been frozen to be dried under a vacuum. In freeze drying, the water is frozen,
followed by its removal from the sample, initially by sublimation (primary drying) and then
by desorption (secondary drying). In this process, the moisture content of the product is
reduced to such a low level that does not support biological growth or chemical reactions
which gives the stability to the formulation. This technique is useful in formulation
development of drugs which are thermolabile and/or unstable in aqueous medium. The
applications of freeze drying are numerous, but it is generally employed when the
requirements demand. It is employed in preservation of temperature sensitive products,
particularly those of biological origin, such as enzymes, blood plasma, vaccines, etc. To
achieve a chemical balance, such as for biological reagents or to provide a practical solution
for certain delivery problems (for example, the packaging of constituents that cannot be
mixed in the liquid state, but which are solidified in successive stages and then freeze dried),
freeze drying is often used. This process has also found uses in implementation of an
important stage of a product (to achieve a certain concentration) or in improvement storage
life and improved marketing of the end product or in resolving certain filling problems. It
may be difficult, for instance, to divide several milligrams of powder into precise vial
dosages, due to the difficulty of measuring tiny amounts, homogeneity, granulation, static
electricity etc. The distribution of the product from the liquid state eliminates such production
problems.

1.1 History
The basic process of freeze-drying food was known to the ancient Peruvian Incas of the
Andes. Freeze-drying, or lyophilization, is the sublimation/removal of water content from
frozen food. The dehydration occurs under a vacuum, with the plant/animal product solidly
frozen during the process. Shrinkage is eliminated or minimized, and a near-perfect
preservation results. Freeze-dried food lasts longer than other preserved food and is very
light, which makes it perfect for space travel. The Incas stored their potatoes and other food
crops on the mountain heights above Machu Picchu. The cold mountain temperatures froze

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the food and the water inside slowly vaporized under the low air pressure of the high
altitudes.
During World War II, the freeze-dried process was developed commercially when it was used
to preserve blood plasma and penicillin. Freeze-drying requires the use of a special machine
called a freeze-dryer, which has a large chamber for freezing and a vacuum pump for
removing moisture. As the use of lyophilization expanded, the process began to be
industrialized. Loire, Stokes, Edwards, and others designed and built the first equipment for
the purpose. Called lyophilization by Flosdorf, the process faced its first major challenge
under Sir Ernst Boris Chain, who used the technique to preserve antibiotics. Given Chains
results turned to lyophilization to prepare vaccines and, later on, to refine blood fractions. By
the mid-1950s, many industries were already using freeze drying to preserve pharmaceutical
and biological products, as were the physicians and surgeons who developed tissue-banking
for plastic and reconstructive surgery. Drs. Hyatt, Bassett, and Meryman of the United States
Navy were among the early pioneers in the field. Over 400 different types of freeze-dried
foods have been commercially produced since the 1960s. Two bad candidates for freezedrying are lettuce and watermelon because they have too high a water content and freeze-dry
poorly. Freeze-dried coffee is the best-known freeze-dried product. There are several
advantages of the freeze drying process to stabilize delicate products (e.g. proteins, peptides,
etc.): Properly freeze dried products (1) do not need refrigeration, (2) can be stored at
ambient temperatures, (3) can be completely reconstituted with water for injection (WFI)
within seconds and (4) are stable over a 2 year shelf life. The drawback, however, is that
freeze drying is an expensive process (long process times, limited throughput) and requires
specialized equipment.

2. Basic Principle
Lyophilization process is based on the principle of sublimation of ice, without entering the
liquid phase. This phenomenon is seen in really cold and dry climes where the snow
sublimating through a process that is similar to evaporation. Whenever there is an interface of
air and water, either liquid or solid, you have molecules trying to leave the water. The
constantly vibrating molecules in a liquid or solid are restrained by other forces, but a water

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molecule will escape the water and enter the air when it moves violently enough. It is called
evaporation from a liquid, and sublimation from a solid. Sublimation is also obvious in the
freezers, where the ice cubes tend to shrink with time. It is also visible in snowfields that
eventually waste away without melting. It is noticed that there is no liquid water, none of the
hard ice that results from melting and refreezing, but the snow still shrinks. Low relative
humidity, as often found on cold days, speeds sublimation, and so does strong sunlight. Snow
absorbs much of the near-infrared portion of sunlight , and that energy accelerates its water
molecules, speeding sublimation.

Figure 1: Phase diagram of water

The phase diagram of water represents that two phases coexist along a line under the given
conditions of temperature and pressure, while at the triple point (0.0075 C at 0.61 kPa or 610
Nm2; 0.01 C at 0.00603 atm), all three phases coexist. If water is cooled below 0 C and
reheated, there are two possibilities. One under normal pressure, or above, it will turn into
liquid. But, at sub-atmospheric pressures, more precisely, below 0.006 atm, there isnt enough
ambient pressure for water to liquefy. So it accepts the heat of sublimation and turns into
vapour. This phenomenon is utilized by freeze drying. This process is performed at
temperature and pressure conditions below the triple point, to facilitate sublimation of ice.
The entire process is performed at low temperature and pressure, so that useful for drying of

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thermolabile compounds. Various important steps involved in lyophilization process which
start from sample preparation followed by freezing, primary drying and secondary drying, to
obtain the final dried product with desired moisture content.

Figure 2: Lyophilization cycle

The concentration gradient of water vapour between the drying front and condenser is the
driving force for removal of water during lyophilization. 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. This critical process temperature is the collapse
temperature for amorphous substance, or eutectic melt for the crystalline substance. During
freezing, ice crystals start separating out until the solution becomes maximally concentrated.
On further cooling, phase separation of the solute and ice takes place. If the solute separates
out in crystalline form, it is known as the eutectic temperature. In contrast, if an amorphous
form is formed, the temperature is referred to as the glass transition temperature.
Determination of this critical temperature is important for development of an optimized
lyophilization cycle. During primary drying, drying temperature should not exceed the
critical temperature, which otherwise leads to meltback or collapse phenomenon in case of
crystalline or amorphous substance respectively.

3. Freeze drying process


A typical freeze-drying process consists of four important stages, that is, pre-treatment,
freezing, primary drying, and secondary drying. In freezing, most of the solvent, typically
water, is separated from the solutes to form ice. The freezing stage typically takes several
hours to finish. Primary drying, or ice sublimation, begins whenever the chamber pressure is

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reduced and the shelf temperature is raised to supply the heat removed by ice sublimation.
During primary drying, the chamber pressure is well below the vapour pressure of ice, and
ice is transferred from the product to the condenser by sublimation and crystallization onto
the cold coils/plates (<50C) in the condenser. Secondary drying is the stage where water is
desorbed from the freeze concentrate, usually at elevated temperature and low pressure.
3.1 Pre-treatment
Pre-treatment includes any method of treating the product prior to freezing. This may include
concentrating the product, formulation revision (i.e., addition of components to increase
stability and/or improve processing), decreasing a high vapor pressure solvent or increasing
the surface area. In many instances the decision to pre-treat a product is based on theoretical
knowledge of freeze-drying and its requirements, or is demanded by cycle time or product
quality considerations. Methods of pre-treatment include: Freeze concentration, Solution
phase concentration, Formulation to Preserve Product Appearance, Formulation to Stabilize
Reactive Products, Formulation to Increase the Surface Area, and Decreasing High Vapor
Pressure Solvents. Similar to cryoprotectants, some molecules protect freeze-dried material.
Known as lyoprotectants, these molecules are typically polyhydroxy compounds such
as sugars (mono-,di-,

and polysaccharides), polyalcohols,

and

their

derivatives. Trehalose and sucrose are natural lyoprotectants. Trehalose is produced by a


variety of plant (for example selaginella andarabidopsis thaliana), fungi, and invertebrate
animals that remain in a state of suspended animation during periods of drought (also known
as anhydrobiosis).
3.2 Freezing
Freezing is a critical step in freeze drying process since the micro structure formed during
freezing determines both the quality of the final product and its processing characteristics,
such as the rate of primary drying and secondary drying. The product must be frozen to low
temperature to a point where it is completely solidified. Freezing the product decreases
chemical activity by decreasing molecular movement.
In general, freezing is defined as the process of ice crystallization from super cooled water.
The freezing process first involves the cooling of the solution until ice nucleation occurs. Ice
crystals begin to grow at a certain rate, resulting in freeze concentration of the solution, a

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process that can result in either crystalline or amorphous solids or in mixtures. Freezing an
aqueous pharmaceutical formulation can be conducted at a temperature at below -35 C.
The phenomena that take place in freezing step are3.2.1 Super-cooling
The retention of the liquid state below the equilibrium freezing point of the solution is termed
as supercooling. It always occurs during freezing often in the range of 10-15C or more.
Super-cooling is of two types,
1. Global super-cooling
It is the process in which the entire liquid volume exhibits a similar level of super cooling.
2. Local super-cooling
In this method, only a small volume of the liquid is super cooled. Super-cooling is a non
equilibrium, meta-stable state, which is similar to an activation energy necessary for the
nucleation process.
3.2.2. Ice-nucleation
Due to density fluctuations from Brownian motion in the super-cooled liquid water, water
molecules form clusters with relatively long-living hydrogen bonds with similar molecular
arrangements as in ice crystals. Nucleation is of two types:
1. Homogeneous nucleation
The limiting nucleation temperature of water is referred to as the homogeneous nucleation
temperature that appears to be at about -40C. At this temperature, pure water sample will
contain at least one spontaneously formed active water nucleus, capable of initiating ice
crystal growth.
2. Heterogeneous nucleation

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In heterogeneous nucleation ice-like clusters are formed via adsorption of layers of water on
foreign impurities.
3.2.3 Ice crystal growth
Once the critical mass of nuclei is reached, ice crystallization occurs rapidly in the entire
system which leads to the formation of stable ice crystals. Once stable ice crystals are
formed, their growth proceeds by the addition of molecules to the interface. As crystallization
begins, the product temperature rises rapidly to near the equilibrium freezing point. After the
initial ice network has formed, additional heat is removed from the solution by further
cooling and the remaining water freezes when the previously formed ice crystals grow. The
number of ice nuclei formed, the rate of ice growth and the ice crystals size depend on the
degree of super-cooling.
3.3 Primary drying
It is characterized by receding boundary layer of ice in the vial. This step traditionally is
carried out at chamber pressures of 40-400 Torr and shelf temperatures ranging from -30C to
-10 C. In this phase the chamber pressure is reduced up to 0.01 to 0.1mbar by introducing
vacuum in to the product chamber. Heat is applied to the product to cause the frozen mobile
water to sublime. The water vapour is collected on the surface of a condenser. The condenser
must have sufficient surface area and cooling capacity to hold all the sublimed water from
batch at a temperature lower than the product temperature. If the temperature of the ice on the
condenser is warmer than the product, water vapour will tend to move towards the product,
and the drying will stop. Sublimation front and the partial pressure of water vapour in the
freeze dry chamber. Since vapour pressure is related to temperature, it is necessary that the
product temperature is warmer than the condenser temperature. The molecules of water move
from higher vapour pressure region in the chamber towards the lower vapour pressure region
in the condenser. It is extremely important that the temperature at which a product is freeze
dried is balanced between the temperature that maintains the frozen integrity of the product
and the temperature that maximizes the vapour pressure of the product. This balance is the
key to optimum drying. The condenser is kept at a low temperature, generally around -60C.
The temperature of the product should be kept as close to the glass transition temperature as
possible for maximum efficiency in drying.

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Figure 3: Comparison of minimum chamber pressure as a function of drying


rate

3.3.1 Differential energy balance in the drying layer

Where,
Ie= Mean density of dry product = 1.526 Kg/m3
CIe = Sp. heat of dry product (Cd) + Sp. Heat of water (Cw), J/kg.K
= 3430 J/kg.K + 4186 J/kg.K
T1 = Temperature of dry layer
KIe = Thermal conductivity of dry Product = 0.552 W/m.K
Ie = Thermal Diffusivity, m2/sec

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Nw = Mass flux of water vapor, kg/m2.sec = Mole flux of water vapor
(Ng,mol/m2.sec) x Molecular weight of water vapor ( Mg = 18 g/mol)
Cg = Sp. Heat of water vapor = 1850 J/kg.K
kf = Thermal conductivity of the frozen material = 2.5 W/m.K
f = Density of ice face= 922.11 kg/m3
3.4 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%. Therefore, continued drying is necessary at warmer temperature to reduce the
residual moisture content to optimum values. This process is called Isothermal Desorption
as the bound water is desorbed from the product. This step is accomplished by raising the
shelf temperature to higher than ambient conditions. The shelf temperature can be raised to
15-300 C, for allowing the water molecules to desorbs under vacuum. The shelf temperature
should not be raised above the product temperature; otherwise degradation of the product
occurs. The product may appear to be dry at the end of the primary drying stage but, the
moisture content may still be 7-8% weight. Secondary drying continues until the desired
moisture content of the product is achieved. The moisture content should be less than or equal
to 2% of the product weight. The product should not be over dried, and should not have final
moisture content below 1.5 %weight in order to preserve the cake structure. Some
chemotherapeutics and antibiotics can have moisture contents as low as 0.1 weight%.
Secondary drying parameters are based on the quantity and nature of residual water in the
product and the absorption, adsorption and desorption processes. It is also important to know
how much heat the product can withstand without degrading and the shelf temperature should
not be raised above this temperature. After the freeze-drying process is complete, the vacuum
is usually broken with an inert gas, such as nitrogen, before the material is sealed.

4. Freeze dryer
There are essentially three categories of freeze-dryers: the manifold freeze-dryer, the rotary
freeze-dryer and the tray style freeze-dryer. Two components are common to all types of
freeze-dryers: a vacuum pump to reduce the ambient gas pressure in a vessel containing the
substance to be dried and a condenser to remove the moisture by condensation on a surface
cooled to 40 to 80 C (40 to 112 F). The manifold, rotary and tray type freeze-dryers

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differ in the method by which the dried substance is interfaced with a condenser. In manifold
freeze-dryers a short usually circular tube is used to connect multiple containers with the
dried product to a condenser. The rotary and tray freeze-dryers have a single large reservoir
for the dried substance.

4.1 Rotary freeze dryer


Rotary freeze-dryers are usually used for drying pellets, cubes and other pourable substances.
The rotary dryers have a cylindrical reservoir that is rotated during drying to achieve a more
uniform drying throughout the substance. Tray style freeze-dryers usually have rectangular
reservoir with shelves on which products, such as pharmaceutical solutions and tissue
extracts, can be placed in trays, vials and other containers.

4.2 Manifold freeze dryer


Manifold freeze-dryers are usually used in a laboratory setting when drying liquid substances
in small containers and when the product will be used in a short period of time. A manifold
dryer will dry the product to less than 5% moisture content. Without heat, only primary
drying (removal of the unbound water) can be achieved. A heater must be added for
secondary drying, which will remove the bound water and will produce lower moisture
content.

4.3 Tray style freeze dryer


Tray style freeze-dryers are typically larger than the manifold dryers and are more
sophisticated. Tray style freeze-dryers are used to dry a variety of materials. A tray freezedryer is used to produce the driest product for long-term storage. A tray freeze-dryer allows
the product to be frozen in place and performs both primary (unbound water removal) and
secondary (bound water removal) freeze-drying, thus producing the driest possible endproduct. Tray freeze-dryers can dry products in bulk or in vials or other containers. When
drying in vials, the freeze-dryer is supplied with a stoppering mechanism that allows a
stopper to be pressed into place, sealing the vial before it is exposed to the atmosphere. This
is used for long-term storage, such as vaccines.

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Improved freeze drying techniques are being developed to extend the range of products that
can be freeze dried, to improve the quality of the product, and to produce the product faster
with less labour.

5. Applications
Freeze-drying (lyophilization), was developed to preserve bioactive molecules (DNA,
enzymes, and proteins), pharma-ceuticals products (antibiotics) and other delicate, solventimpregnated materials. Freeze-drying is becoming an increasingly popular method for the
long-term preservation of various biological materials. Although today a great variety of
foods, pharmaceuticals, etc. are produced by lyophilization, a successful application for long
term preservation of living systems, like cells, is still one of the greatest challenges for
scientists in this field. Continuous innovation and process optimization have increasingly led
to more and more new applications of this process on an industrial scale. Freeze-drying
appears, therefore, as a promising technique for dehydration of thermal-sensitive materials,
such as fruits. Processing conditions have an influence on the quality criteria used to evaluate
freeze-dried fruits, and on freeze drying time. In fact, two criteria (rehydration and texture)
are closely linked with the ultimate use of the freeze-dried product and cannot be considered
as absolute criteria. Dehydrated fruits are intended primary to be added to products such as
corn flakes, cereal bars, ice cream, pastry sauces, etc. Freeze drying is used extensively in
food and pharmaceutical industries extensively.
5.1 Food industry
The technology was applied to consumer food products after the end of the war. Coffee was
one of the first freeze-dried products to be marketed on a large scale. Today, many fruits,
vegetables, meats, eggs, and food flavourings are freeze-dried.
Freeze-dried food has many advantages. Because as much as 98% of the water content has
been removed, the food is extremely lightweight and this significantly reduces the cost of
shipping. This also makes it popular with boaters and hikers who have to carry their food
with them. Because it requires no refrigeration, shipping and storage costs are even further
reduced. Freeze-dried food is also relatively contamination-free since the dehydration process
makes it virtually impossible for yeast and potentially harmful bacteria to survive. Finally,
since the physical structure of the food is not altered during the freeze-drying process, the

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food retains much of its colour, shape, texture, and flavour when it is prepared for
consumption by reintroducing water. This makes it more attractive to consumers than food
preserved by some other methods.
5.1.1 Raw materials
Some foods are extremely well-suited to the freeze-drying process, others do not fare so well.
Liquids, thin portions of meat, and small fruits and vegetables can be freezedried easily.
Coffee is the most common freeze-dried liquid. Chunks or slices of shrimp, crab, lobster,
beef, and chicken can be freeze-dried. They are often mixed with vegetables as part of soups
or main course entrees.

Figure 4: A freeze dried fruit platter retains flavor and texture well

Almost all fruits and vegetables can be freeze-dried, including beans, corn, peas, tomatoes,
berries, lemons, oranges, and pineapples. Even items like olives and water chestnuts can be
processed this way.
Thick portions of meat and larger, whole vegetables and fruits cannot be freeze dried with
any success. With many other foods, it is simply not economical to preserve them by freeze
drying.

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5.1.2 Manufacturing process
A freeze-drying processing facility is usually a large plant with modern equipment. It food
handling areas must be approved by the United States Department of Agriculture, and the
company and its employees must adhere to government regulatory procedures. The plant may
include a receiving and storage area for raw foods that arrive at the plant in bulk; a food
cooking area for those foods that must be cooked before processing; a large area with several
large freezing and drying chambers; and a packaging area. The facility may also include a
research area where improved methods of freeze-drying foods are developed, and a test
kitchen where new preparation techniques to improve the final taste, quality, and texture of
the food are tried. Some plants are dedicated to freeze-drying only one product like freezedried coffee. Others process a wide range of meats, vegetables, and fruits. Nonfood products
such as chemicals and pharmaceuticals are usually processed in separate plants from food
products. The freeze-drying process varies in the details of temperatures, times, pressures,
and intermediate steps from one food to another.

5.1.3 Difference between freeze drying and dehydration


While both types of food- dehydrated and freeze dried- are essentially dried, they differ in a
few important ways. One of the most important differences is the process used to create the
final product.
When food is dehydrated, the pieces are placed into a warm environment that removes much
of the water content. This may be done naturally by laying the cut fruit in the sun on a hot
surface, or mechanically by running the food through machinery that is designed to dehydrate
the food. In either case, there are no added chemicals to encourage the process and no sugar
added to the food.
While freeze-fried food is also dehydrated, the process for preparing it is different and
somewhat more complicated. Before the drying process begins, the food is frozen. It is then
placed into a chamber that makes use of a vacuum to gradually extract the water content.
Heat is applied in the chamber and set at a temperature that allows the frozen food to quickly
thaw while the vacuum extracts the water. The end result is a dried food that retains the taste
of fresh and also develops a crispy texture. While both types of dried food have a long shelf

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life, there is a significant difference in how long they will keep under normal conditions. In
general, dehydrated food will retain their taste and flavour for a period of one year. Freezedried food can easily be stored for several years, assuming that the food is sealed in a
container that is airtight and moisture free. The texture of the food is also often different.
Food that has been dehydrated has a more pliable texture, while freeze-dried varieties tend to
be crisper and crunchier.

Figure 5: Freeze dried and dehydrated fruits differ visibly in terms of texture
and colour

5.2 Pharmaceutical industry


Pharmaceutical companies often use freeze-drying to increase the shelf life of the products,
such as vaccines and other injectables. By removing the water from the material and sealing
the material in a vial, the material can be easily stored, shipped, and later reconstituted to its
original form for injection. Another example from the pharmaceutical industry is the use of
freeze drying to produce tablets or wafers, the advantage of which is less excipient as well as
a rapidly absorbed and easily administered dosage form.

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Figure 6: Scanning Electron Microscopy (SEM) analysis of freeze dried


pharmaceutical product

5.3 Technological industry


In chemical synthesis, products are often freeze-dried to make them more stable, or easier to
dissolve in water for subsequent use.
In bio-separations, freeze-drying can be used also as a late-stage purification procedure,
because it can effectively remove solvents. Furthermore, it is capable of concentrating
substances with low molecular weights that are too small to be removed by a filtration
membrane.
Freeze-drying is a relatively expensive process. The equipment is about three times as
expensive as the equipment used for other separation processes, and the high energy demands
lead to high energy costs. Furthermore, freeze-drying also has a long process time, because
the addition of too much heat to the material can cause melting or structural deformations.
Therefore, freeze-drying is often reserved for materials that are heat-sensitive, such
as proteins, enzymes, microorganisms, and blood plasma. The low operating temperature of
the process leads to minimal damage of these heat-sensitive products.

5. 4 Other applications
Organizations such as the Document Conservation Laboratory at the United States National
Archives and Records Administration (NARA) have done studies on freeze-drying as a
recovery method of water-damaged books and documents. While recovery is possible,
restoration quality depends on the material of the documents. If a document is made of a
variety of materials, which have different absorption properties, expansion will occur at a

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non-uniform rate, which could lead to deformations. Water can also cause mold to grow or
make inks bleed. In these cases, freeze-drying may not be an effective restoration method.
In bacteriology freeze-drying is used to conserve special strains.
In high-altitude environments, the low temperatures and pressures can sometimes produce
natural mummies by a process of freeze-drying.
Advanced ceramics processes sometimes use freeze-drying to create a formable powder from
a sprayed slurry mist. Freeze-drying creates softer particles with a more homogeneous
chemical composition than traditional hot spray drying, but it is also more expensive.
Freeze drying is also used for floral preservation. Wedding bouquet preservation has become
very popular with brides who want to preserve their wedding day flowers.
A new form of burial which previously freeze-dries the body with liquid nitrogen has been
developed by the Swedish company Promessa Organic AB, which puts it forward as an
environmentally friendly alternative to traditional casket and cremation burials.

6. Possible improvements
Despite successful operation over many decades, tray freeze dryers have three significant
disadvantages. First, loading and unloading is labor-intensive, especially since large units
may contain several hundred trays. Second, the freeze-dried cake removed from the trays
often requires grinding to convert it to a free-flowing granular product. Third, the formation
of a skin of dried product on the surface of the tray hinders the passage of vapor, making
this method of freeze drying very slow. Research can be dedicated towards developing a
quicker and less labor-intensive freeze drying process that can produce free-flowing powders
from a single process vessel. Known as Active Freeze Drying technology, the new process
uses continuous motion to improve mass transfer and hence cut processing time, while also
eliminating the need to transfer product to and from drying trays and downstream size
reduction devices.
Active Freeze Drying method can be developed to be used commercially at lower costs. Here,
te product is first frozen in a specially-designed drying vessel fitted with an agitator. Whether
the material to be dried starts off as a liquid, granular solid or paste, the forced motion inside
the drying vessel ensures that it freezes in the form of free-flowing solid granules. Once the
product is fully frozen, vacuum is applied and sublimation starts. The initially coarse granules

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gradually shrink as the ice structure connecting the frozen material sublimes away, yielding a
loose powder consisting of dry particles. Too much vapour creation is counterproductive to
the process, so sensors can be developed to avoid this problem.

7. Conclusion
With hundreds of variants actually used in drying of particulate solids, pastes, continuous
sheets, slurries or solutions, it provides the greatest diversity among food engineering unit
operations. These changes alter the physical properties such as colour and structure. They can
also develop undesirable biochemical reactions, such as deterioration of aroma compounds or
degradation of nutrients. All these physical and biochemical changes certainly diminish
products quality and reduce process efficiency. Freeze-drying is a specific drying method
which allows obtaining dried materials with features typical of raw material.
Freeze-drying is used for the reliable preservation of a wide variety of heat-sensitive products
and demands the highest standards of reliability and control. In addition to food products, it
is suitable for other goods, including: flowers, cultured microorganisms, bulk
pharmaceuticals, medical devices, and cosmetics, specially chemicals, pigments and
enzymes. The most important in this process are time, temperature and pressure. If they are
well defined they may indeed affect the quality of the final product. Unfortunately, high
porosity of dried materials has a negative effect on storage stability. Thus, freeze-dried
materials need to be stored in a hermetic package. The freeze-drying process is still
expensive, which restricts its application on wide range in the food industry. New technical
solutions are applied to modify the freeze-drying process and make it time- and costeffective, e.g. if we replace traditional heating source by microwaves radiation or we use a
spray nozzle in dryer chamber. Another solution to limit process time is to use pre-treatment
as blanching, dehydration by infrared radiation or osmotic dehydration.
References:
1. Barbaree, J.M. and A. Sanchez. 1982. Cross-contamination during lyophilization.
Cryobiology 19:443-447.

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2. Barbaree, J.M., A. Sanchez and G.N. Sanden. 1985. Problems in freeze-drying: I. Stability
in glass-sealed rubber stoppered vials. Developments in Industrial Microbiology 26:397-405.
3. Barbaree, J.M., A. Sanchez and G.N. Sanden. 1985. Problems in freeze-drying: II. Crosscontamination during lyophilization. Developments in IndustrialMicrobiology 26:407-409.
4. Flink, J.M. and Knudsen, H. 1983. An Introduction to Freeze Drying. Strandberg
Bogtryk/Offset, Denmark.
5. Flosdorf, E.W. 1949. Freeze-Drying. Reinhold Publishing Corporation, New York.
6. Greiff, D. 1971. Protein structure and freeze-drying: the effects of residual moisture and
gases. Cryobiology 8:145-152.
7. Greiff, D. and W.A. Rightsel. 1965. An accelerated storage test for predicting the stability
of suspensions of measles virus dried by sublimation in vacuum. Journal of Immunology
94:395-400.
8. Greaves, R.I.N., J. Nagington, and T.D. Kellaway. 1963. Preservation of living cells by
freezing and by drying. Federation Proceedings 22:90-93
9. Heat and mass transfer in atmospheric freeze drying,
http://serve.me.nus.edu.sg/arun/file/teaching/ppt-mass-tr(revised)3.pdf
10. General principles of freeze drying, http://freezedrying.com/freeze-dryers/generalprinciples-of-freeze-drying/#2