EFFLORESCENCE

Introduction:
• Efflorescence is the loss of water of crystallization from a hydrated salt to the
atmosphere on exposure to air.

• The substance itself give up water.

• The spontaneous dehydration of a compound is called efflorescence.
• The loss of water of crystallization by hydrated crystalline substance with water of
crystallization) to form anhydrous salts or hydrate with less molecules of water of
crystallization is called efflorescence.

Hydrates:
• Solids that contain water molecules as part of their crystalline structure.
• The water in the hydrate is known as the water of hydration or the water of
crystallization.
• The combination of water molecules with molecules of a compound results in a
hydrate.
• A large number of compounds crystallize in hydrated form. e.g.,
CuSO4 combines with 5 molecules of water
Na2SO4 combines with 10 molecules of water
MgSO4 combines with 7 molecules of water
FeSO4 combines with 7 molecules of water
• Presence of water of crystallization is not essential for crystal structure, as Sodium
chloride, potassium nitrate and many other compounds have definite crystal structures
without water of crystallization.

Principle:
• If the vapor pressure of a hydrated salt is greater than the pressure exerted by the water
vapors in the surrounding atmosphere then the salt will tempt to attain equilibrium
with its surroundings, and will therefore tend to lose water to form a lower hydrate or
an anhydrous salt.
• This phenomenon is called as Efflorescence.
• For example, the vapor pressure of washing soda (Na 2CO3.10H2O) normally exceeds
that of the water vapor in the atmosphere, these salts effloresce (i.e., lose all or part of
their water of hydration), and their surfaces assume a powdery appearance.
• Hydrated cupric sulfate, or blue vitriol (CuSO4.5H2O), the aqueous vapor pressure of
which is lower, undergoes efflorescence only if the air in contact with it is relatively
dry.
• A salt such as copper sulfate may form more than one hydrate, each of which
possesses its own definite vapor pressure at a given temperature. The following
hydrates of copper sulfate are known:
 CuSO4.5H2O, CuSO4.3H2O and CuSO4.H2O
• When certain substances of low vapor pressure, such as CaCl 2. H2O, are exposed to
air, they form higher hydrates. Such salts may be used in the removal of moisture from
air or other gases.

Example:
• Pressure of water vapor in the atmosphere is about 13.3X10² N/m² at 293 k.
• Therefore, the hydrates with vapor pressure greater than this will show efflorescence
and will be unstable, provided that the lower hydrate formed still exert a vapor
pressure greater than the surrounding atmosphere.
• If this is not so, the water will be taken up from the atmosphere by the lower hydrate
as fast as it is formed and the final equilibrium will depend on the rates at which water
is lost or taken up by the two hydrates.
• E.g.
o The behavior of various forms of sodium carbonate.
o Sodium Sulphate
o Certain salts of quinine

• The Vapor pressure exerted by the Dehydrate is much greater than that of normal
atmosphere and it loses water by efflorescence and is converted to monohydrate.
• The vapor pressure of it is still above that of atmosphere, but further apparent loss of
water does not occur because the anhydrous salt is rehydrated at a faster rate than
dehydration of the monohydrate.
• The vapor pressure of hydrated salts, and therefore the rate of efflorescence increases
with rise in temperature.

Applications:
• Hydrated drug on weight basis is less potent but when it is converted by efflorescence
to its corresponding lower hydrates, or anhydrous form then its potency can be
increased.
• Anhydrous form is easy to handle during manufacturing process.

Precautions:
• The container that prevents the loss of water vapors should be used to avoid the
instability.
• Store is a cool place because greater is the temperature greater is the release of water
of crystallization.
 DELIQUESCENCE
Introduction:
• It is derived from the Latin word “deliquescere” literally “to start melting away”, from
“liquere” that is “to be liquid”. So it means, to dissolve gradually by absorbing
moisture from the air.
• HYGROSCOPIC: A substance is hygroscopic if it readily absorbs water from the
atmosphere and forms a hydrate.
• DELIQUESCENT: A substance is deliquescent if it absorbs water from the air until
it forms a solution.
• This process is reverse of efflorescence.
• Both these terms are used to indicate that a material takes up water vapors from the
atmosphere and is converted to a more hydrated form. In case of hygroscopic
substance, the more hydrated state is till a solid but in deliquescence there is eventual
formation of a liquid phase i.e., a solution.
• Such substances are said to be DELIQUESCENT, and the process is termed
DELIQUESCENCE.
• Many pharmaceutical crystalline solids absorb water vapor readily from the
environment and are considered to be hygroscopic
• Uptake of unacceptable amount of water can cause adverse effects on physical and chemical
stability of the product
o Phase transformations
o Chemical degradation
o Variation in disintegration
o Dissolution rate

Definition:
It is a phenomenon of taking up water vapor from the atmosphere when exposed to an
atmosphere with higher partial pressure than the partial pressure of the substance to form a
more hydrated liquid phase.

Deliquescent Materials:
• Deliquescent materials are substances that have a strong affinity for moisture and will
absorb relatively large amounts of water from the atmosphere if exposed to it forming
a liquid solution.
• calcium chloride
o magnesium chloride
o sodium hydroxide
o Potassium hydroxide
o Sodium lactate
o Ferric ammonium citrate
o Potassium bicarbonate

Process:
 • Water vapor from the air condenses on the surface of the solid and forms a ver y
concentrated solution which has a vapor pressure much lower than the average vapor
pressure of the water vapor in the air.
• The solution therefore continues to take up water until its vapor pressure equals the
pressure of the water vapor in the air.
• CRH the deliquescent point is often termed as the critical relative humidity
• The critical relative humidity (CRH) of a salt is defined as the relative humidity of
the surrounding atmosphere (at a certain temperature) at which the material begins to
absorb moisture from the atmosphere and below which it will not absorb atmospheric
moisture.
• below CRH, solids absorb minimal amounts of moisture at the surface
• above CRH, the solid starts dissolving in the condensate film
• The absorption process stops when vapor pressure of the resultant solution is equal to
the vapor pressure of the atmosphere.
• If the vapor pressure is further increased, complete dissolution of the solid and
solution dilution will ultimately occur.

Disadvantages:
• As in deliquescence water is picked up by the sample, unacceptable changes in
appearance and performance occur.
• Chemical stability often changes dramatically.
• Physical implications such as decrease in dissolution, variation in water content in the
final product, crystallization of the formulation components and powder caking can
occur.
• Chemical reactions such as hydrolysis and oxidation could also be accelerated by
water sorption.
• In systems containing more than one deliquescent component, the RH will be lowered,
leading to dissolution at unexpectedly low RH conditions.
• When excipients having relatively low CRH values are used they can affect the
chemical and physical stability of a solid dosage form, even if the API’s CRH is not
exceeded.
• The liquid water can dissolve the API, making stability much worse.
• Deliquescence lowering is independent of the ratio of the deliquescent components
and therefore is of concern for any formulation containing two or more deliquescent
compounds
• RH fluctuation will lead to cycles of deliquescence and efflorescence, which will lead
to particle agglomeration and caking.
Methods of Prevention:
• Tight containers protect the contents from contamination by extraneous liquids,
solids or vapors, from loss, from efflorescence, deliquescence or evaporation under
ordinary and customary conditions of handling, shipment, storage and distribution.
• Solid compounded formulations, an inert, powdered ingredient that will
preferentially absorb water, maybe added to the formulation. E.g. Light MgO.
• In most cases it is found unnecessary to add any inert powder in prescriptions for
capsules containing deliquescent drugs, it is imperative to use an air tight container,
such as a screw-top glass capsule vial.

Storage Precautions:
• Store the product in low humidity environment.
• Well closed containers should be used.
• Well filled container: Limits the volume of the atmosphere in the container and
therefore further reduces the uptake of moisture by the product.
• A Drying agent maybe placed inside the container e.g. Silica gel, often used in small
packets.

Applications:
• Owing to their very high affinity for water, these substances are often used as
desiccants; these compounds are used in the chemical industry to remove the water
produced by chemical reactions.
• As Desiccants Due to their very high affinity for water, these substances are often
used as desiccants, an application for concentrated sulfuric and phosphoric acids
• Commonly used to protect against moisture damage.
• Used in hygroscopic cargo such as cocoa, coffee and various nuts and grains, that are
particularly susceptible to mold and rot when exposed to condensation and humidity.
• These substances are used in the chemical industry to remove the water produced by
chemical reactions to increase the yields.
• The effectiveness of calcined CaCl 2 in settling road dust is result of its
deliquescence.
• When spread in form of a powder or flakes, it absorbs more than its own weight of
water and forms a liquid that keeps the road wet.
• Used in chemical industry to remove the water produced by chemical reactions to
increase the yields.
• The property of deliquescence is utilized in the laboratory to dry substances; calcium
chloride is often employed for this purpose.
 LYOPHILIZATION (Freeze Drying)
Introduction:
• The process of isolation a solid substance from solution by freezing the solution and
vaporizing the ice away under vacuum conditions.
• It is the sublimation from frozen substance.
• It involves triple point of substance.

Triple Point:
It is the point having the definite temperature and pressure at which the solids, liquids
and vapor phases of a chemical entity are able to co-exist.

Steps Involved:
The process of lyophilization is completed in the following stages.

• Pre-treatment:
o Freezing of solids:
Before applying the vacuum, he liquid is firstly frozen, this process is called pre-
freezing and is done by following ways:
▪ Shell Freezing:
In this method he liquid is taken in a bottle and is rotated slowly, horizontally
in a refrigerator bath. So that material freezes as a thin shell (layer) along the
walls of the bottle. In this way not only the surface area for sublimation is
increased but also heat transfer is increased.
▪ Vertical Freezing:
In this method, he bottles are first chilled and then rotated individually in
vertical position in the presence of stream of very cold air. So, by this process
small crystals of ice are formed. Moreover this process is very rapid.
o Drying:
After the pre-freezing, the substance is dried there are two types of freezing:
▪ Primary drying:
It means to supply the latent heat of vaporization. The apparatus used for this
process is “vacuum oven” or container attached to individual outlet. The latent
 heat of sublimation of substance is provided and so vapors formed are
removed. By this process 99.5% moisture is removed.
▪ Secondary drying:
After primary drying the substance is subjected to vacuum drying to remaining
0.5% moisture. And this is called as secondary drying. Temperature during this
drying is raised to 500C to 600C.
• Annealing
Increasing temperature but below melting and then holding to allow crystal
growth is called as annealing. Some amorphous products (such as mannitol or glycine)
form a metastable glass with incomplete crystallization when first frozen. These
products can benefit from a thermal treatment process, which is also called annealing.
During annealing, the product temperature is cycled (for example: from -40C to -20C
for a few hours and then back to -40C) to obtain more complete crystallization.
Annealing has the added advantage of larger crystal growth and corresponding shorter
drying times.

Packaging:
The packaging of freeze dried product is very important b/c the freeze dried products
must be protected from moisture. For this purpose the product is packed in vacuum container
or the closing is carried out under controlled conditions of atmosphere to avoid contact with
moisture.

Properties of FD Material:
• Amorphous and highly porous
• Takes moisture immediately and tends to crystallize
• Enormous Surface area

Advantages of Freeze-Dried Products:

• Product is dried without any elevated temperature.
• This process is also good for oxygen and sensitive drugs.
• The product is in porous form, that’s why it can be reconstituted rapidly.
• Constitutes of the dried materials remained homogenously dispersed.
• Sterility of the product can be achieved and maintained.
• Due to low temperature enzyme activity and decomposition (hydrolysis) is stopped.
Disadvantages of Freeze-Dried Products:
• Volatile compounds may be removed
• Single operation is very expensive
• The process is slow
• Stability problem associated with individual drugs

Desired Characteristics of Freeze-Dried Product:

The freeze-dried product should have:

• Sufficient strength
• Uniform colour
• Sufficient dryness
• Sufficient porosity
• Sterility
• Free of pyrogens
• Free of particulates
• Chemically stability

Applications:
• Drug prevention method as
o Lowers water activity
o Reduces potential for microbial growth
• Dry the heat sensitive products
o Biotechnology products
o Biological drugs (proteins, seras etc)
• Long shelf life of drugs
• Enzymes (hylauranidase) and hormones (insulin) are also dried by this process.
• Amorphous and possesses enormous surface area
• This process is used for the drying of proteins and peptides.
• This process is used in recombinant DNA technology. Hence, used for the
manufacturing of various pharmaceuticals and biological products which are
thermolyophils.

Difference between Sublimation and Lyophilization:

In sublimation the K.E. of the molecule is very high and so molecules are directly
converted into vapors. In lyophilization is carried out in controlled temperature and pressure.
The K.E. of the molecule is not sufficient to convert it in to vapors, so in this process the
substance is first converted into liquid and then to vapors.
 ELUTRITION
Definition:
• Elutriation is the process in which the particles of the fluid move in a direction
opposite to that of the sedimentation. (Downward movement)
• Process of separation of a substance into powder of different degree of fineness by
stirring the substance with large volume of liquid in which it is insoluble and
withdrawing the liquids at different heights

Explanation:
• In gravitational sedimentation the particles will move vertically downward while the
fluid travels vertically upward.
• If the velocity of the fluid is less than the setting velocity of the particles, then the
particles will move downward against the stream of fluid. If the setting velocity of
particles is less than the velocity fluid, the particles will move upward.
• In other words, small size particles will move upward while the large size particles
will move downward.
• So, Elutriation is the process of separation of fine particles from course particles. The
particles size can also be measured by this process. The air Elutriation usually give
sharper fractions of small and large particles then water Elutriation.

Apparatus Used:
The apparatus used for Elutriation process is called as Elutriator. They are of two
types:

• Gravitational Elutriation
o In gravitational Elutriation the fluid particles move downward due to
sedimentation (force of gravity) while the lighter particles remain upward.
• Centrifugal Elutriation
o Centrifugal Elutriation causes the fluid stream to rotate under high centrifugal
force to suspend the particles.
o These particles which are too large to rotate with direction of flow of fluid,
separates out on the wall of the elutriator. However, the fine particles move
easily with the stream of fluid.
o Centrifugal Elutriator is again of two types:
▪ Darrclone classifier
▪ Sharp less super classifier
o The sharp less super classifier is useful for high speed separation of fine
particles. It has a capacity of 250lb/hr and operates on air flow of about 100
cubic feet/min at maximum speed of about 50,000 rpm.
Uses:
• Heavy and light Kaolin can be separated by this process, because the particles of
heavy Kaolin move downward and those of the light Kaolin move upward.
• It is usually used following a size reduction process with the objective of separating
oversize particles which may be returned for further grinding.

EXSICCATION
Definition:
• It is the process of accelerating the rate of efflorescence by increasing the temperature
in order to remove the water of crystallization from a hydrated salt.
• The process of removing water of crystallization that is combined water from
substance and temperature is required to remove water from different compounds.
• It may be regarded as process of Efflorescence, controlled and accelerated, but is
applied in cases where water is not normally lost by efflorescence.

Process:
• Exsiccation may be carried out by taking a weighed amount of the substance in a
tarred dish (weight of dish is subtracted from the weight of substance, or dish is auto-
zeroed)
 • It is then heated on a water bath, sand bath or in an oven with continuous stirring until
a constant weight is obtained and there is no further loss in weight.
• No further loss in weight indicates that exsiccation has been completed and no further
water loss can take place
• Mostly a sand-bath or air oven is used for this process.

Principle:
• The principle involved in the process of exsiccation are the same as those in the
process of efflorescence.

Objectives:
• To reduce the bulk of substance.
• Preparing pills which may contain any of the substance (having water of
crystallization) e.g. Ferrous sulphate, Potassium alum etc.
• So by this process of exsiccation we dry the chemicals by removing their water of
crystallization and then by using dried salts we reduce the difficulty of making our
medicine, as well as the size of pill.
• This process is particularly performed to expel the water of crystallization and to
increase the comparative strength of the exsiccated chemical to the crystalline
chemical.

Example:
• The temperature required to remove the water of crystallization is very important and
varies widely.
o For example, in CuSO4.5H2O, when heated at 30°C loses two molecules of
water of crystallization forming CuSO4.3H2O
o At 100°C it loses two more water molecules resulting in CuSO 4.H2O
o The last water molecule is removed at 200°C thus forming anhydrous CuSO 4.
• Some exsiccated substances are not necessarily anhydrous.
o For example, ferrous sulphate (FeSO4.7H2O) when heated at about 100-105°C
loses 6 molecules of water of crystallization.
o When further heated to remove the last water molecule, its decomposition
takes place.
o Hence, FeSO4.H2O is called exsiccated ferrous sulphate.
• If its exsiccation is carried out under vacuum, then anhydrous FeSO4 can be obtained
below 100°C.
o The examples of exsiccated salts used in pharmacy are exsiccated ferrous
sulphate, exsiccated copper sulphate, exsiccated sodium sulphate, exsiccated
magnesium sulphate, exsiccated sodium carbonate, exsiccated sodium
phosphate and exsiccated alum etc.
o As the exsiccated salts are very hygroscopic, they must be stored in air-tight
containers.
Methods:
There are general two methods of exsiccation or drying moist bodies.
1. In one their humid parts are exhaled by heating
2. In other water is absorbed by different substances

Exsiccation is generally performed by means of heat by:

• Coction / Boiling:
o This is a process of drying by heating also named as process of boiling. During
this process it is important to take care of the heat level, at the close of the
operation (process) the fire should be gradually suppressed otherwise the
matter being left dry will be heated beyond the adjusted degrees and then the
exsiccated substance can be damaged.
o This method is Used for Fluids only.
• Isolation:
o Insolation or properly exhalation is effected by exposing the substance to the
sun, till it is sufficiently dried. There is nothing particularly necessary to be
observed, except to increase the surface of the matter to be much exposed to
the sun.
o For in proportion the process of exsiccation will be completed in greater or
lesser time.
o This Method is useful for both solids and liquids.
• Torrificcation:
o Torrification (or sometimes called Toasting) is a process of exposing solid
substance to the heat of the fire at such distance that it will not be endangered.
They are being burnt in order to make them of sufficient dryness to make them
in powdered form.
o Only for Solids.

Conditions Required for Exsiccation:

1. Temperature:
• Temperature is very important to be controlled in the process of exsiccation
because as we increase or decrease the temperature the molecules of water are
evaporated from the crystals. Specific temperature for specific crystal remove
specific amount of water molecule.
2. Moisture:
• It is very important to control the environmental conditions when we are about
to exsiccate a crystal to remove the water of crystallization.
• If the environment is not moisture free then after exsiccating the crystal the
exsiccated produced might again react with the water contents of the
environment and again become hydrated.
• As we know that our aim is to exsiccate a crystal and to remove the water
contents so to achieve this aim we need to keep our environment moisture free.
 • After exsiccating a crystal, we should immediately transfer the exsiccated
product in a close air tight containers or bottles.

Applications:
• Exsiccation is carried out to get an anhydrous product required in the formulation of
pharmaceuticals.
• After the removal of water, the bulk and weight of the drug is reduced and they can be
easily administered/used in manufacturing.
• Potency of drug is increased after the removal of water.
• After exsiccation fine powder is obtained which is easy to handle.
• These exsiccated chemicals are use in the formation of inhalations, sprays, syrups,
mouth washes.
• These exsiccated chemicals are used to prepare medicines to treat microbial, malarial,
fungal and algal infections.
• Some of these exsiccated chemicals are used to treat constipation.

IGNITION
General Introduction:
• It is also called as incineration.
• It is the process by which an organic substance is strongly heated until whole of the
carbonaceous matter burns and an inorganic residue known as Ash is left behind.
OR
The process in which a synthetic compound or drug is burnt at high temperature on
electric furnace to remove organic substance (carbon) and left behind he inorganic
substance and residue as ash is called as ignition.
• This is a process of heating the organic substances in excess of air, until all the Carbon
atoms have burnt as CO2 and residue of inorganic matter (Ash) is left behind. The
residue is called as Ash and the process as Ashing.
• On laboratory scale ignition is carried out in silica or platinum crucibles.
• It consists of strongly heating ("igniting") a sample of the material at a specified
temperature, allowing volatile substances to escape, until its mass ceases to change.
This may be done in air, or in some other reactive or inert atmosphere.

Principle:
• The simple test typically consists of placing a few grams of the material in a tarred,
pre-ignited crucible and determining its mass, placing it in a temperature-controlled
furnace for a set time, cooling it in a controlled (e.g. water-free, CO2-free) atmosphere,
and re determining the mass.
Explanation:
• Ignition is a simplest type of gravimetric analysis which is used for the separation of
organic and inorganic compounds.
• In this process, weighed quantity of the solid substance is ignited in glass crucible in
electric furnace. The substance is ignited on specific temperature for definite time.
• After ignition a desiccator containing a suitable desiccant and allow to cool for 25-30
minutes and then the contents are weighed.
• The crucible and the contents are again ignited at the same temperature for 30 minutes.
• The ignition is continued until a constant weight of inorganic ash is obtained.

Applications:
• This process is mainly used for the standardization of organic substances and crude
drugs by means of gravimetric analysis.
• Used to determine impurities of organic salts of alkali metals such as tartarates,
citrates, Benzoates and many drugs.
• Purity of a drug is determined by its ash content.
• Zinc ointment on ignition leaves only zinc oxide.

SUBLIMATION
Definition:
The process of converting solid substances in to vapours by heating and then
condensing it back to the solid state, without passing it through the intermediate liquid state, is
called sublimation.

Explanation:
• The condensed solid is called sublime.
• Usually the solid first coverts in to liquid state before being converted in to vapour
state but in sublimation liquid phase do not exist.
• Thus,
Triple point:
• The point having a different pressure and temperature at which the solid, liquid, and
vapour phases of a chemical entity are able to co-exist indefinitely is called triple
point.

Principle:
A solid sublime only when the pressure of its vapour is below that of the triple point
for that substance. This principle can be explained by following graph.

• The line OA indicates the melting point of the substance and along this line solid and
liquid is at equilibrium. On right side of this line only liquid exists while on left side
only solid exists.
• The line OB indicates the vapour pressure of the solids vapours and this curve is called
vapour pressure curve. Above this line only liquid exists and below this only vapour
present.
• The line CO is called sublimation curve and represents the conditions of temperature
and pressure for the co-existence of solid and vapour phase.
• To right side of this line only vapour exists and on left side of line only solid exists.
• The point O the intersection of three lines is called triple point. And the graph shows if
the vapour pressures of vapour, formed by the solid, less than the triple point, it will
directly pass from solid to vapour and vapour to solid.

Procedure:
• The impure substance is placed in the china dish which is then gently heated on the
stand bath. The dish is covered with the perforated filter paper over which is placed an
inverted funnel.
• The surface of which may be kept wet by covering it with wet filter paper or cotton
plug. The vapour rising from, the solid pass through the holes in the filter paper and
are deposited as pure solid on the wall of the funnel. The filter paper performs two
functions
• It does not permit the sublime substance to drop back in to the dish.
• It keeps the funnel cool by cutting off the direct heat from the dish.
Pharmaceutical Applications:
• Sublimation is very helpful in separating volatile substances from nonvolatile solids.
In this way pure substance are obtained which are used in various processes.
• Some valuable chemical substances such as naphthalene, camphor, and benzoic acid
etc are purified by this process.

FUSION
Definition:
• It is the process by which the solids get converted into liquids without the addition of
any solvent.
• The process of liquefying a substance by heat without the aid of a solvent is called
fusion.
• In other words, it is defined as the process of heating the solids until they melt.

Explanation:
• In a pure crystalline solid, this process occurs at a fixed temperature called the melting
point
• An impure solid generally melts over a range of temperatures below the melting point
of the principal component.
• Amorphous (non-crystalline) substances such as glass melt by gradually decreasing in
viscosity as temperature is raised, with no sharp transition from solid to liquid.
• The structure of a liquid is always less ordered than that of the crystalline solid and,
therefore, the liquid commonly occupies a larger volume
• Thermal fusion of a given mass of a solid requires the addition of a characteristic
amount of heat, the heat of fusion
• In the reverse process, the freezing of the liquid to form the solid, the same quantity of
heat must be removed.
 • The heat of fusion of ice, the heat required to melt one gram, is about 80 calories; this
amount of heat would raise the temperature of a gram of liquid water from the freezing
point (0° C, or 32° F) to 80°C (176° F).

Applications:
• Fusion is done to purify certain solid and semisolid substances e.g., substances like
Bees wax, hard paraffin, soft paraffin and wool fat are heated to melt and filtered
while hot to remove the dissolved impurities. Then cooling is done to obtain a product
free from dissolved impurities.
• This method is also applied for the preparation of ointments when they contain solids
and semisolids in the formulation. All the substances are first molted and then cooled
slowly with constant stirring until a uniform product is obtained. To avoid
overheating, the substances with higher melting points are melted first to which
substances with lower melting points are added.

CALCINATION
Origin:
• The process of “calcination” derives its name from the Latin “calcinare” (to burn
lime).
• The name is given due to its most common application, the decomposition of calcium
carbonate (limestone) to calcium oxide (lime) and carbon dioxide, in order to produce
cement.

Definition:
• Calcination is the process in which the inorganic substances are strongly heated so as
to remove their volatile contents and a fixed residue are obtained.
• The IUPAC defines it as: “Heating to high temperatures in air or oxygen”.
• The calcination process normally takes place at temperatures below the melting point
of the product materials.

Examples:
Few examples of calcination processes are given below:

• Decomposition of carbonate minerals, as in Calcination of Limestone to drive off

Carbon dioxide to produce cement.
• Decomposition of hydrated minerals, as in Calcination of Bauxite and Gypsum to
remove crystalline water as water vapor.
• Removal of Ammonium ions in the synthesis of Zeolites.
Types:
• Actual Calcination
o Actual calcination is that brought about by actual fire, from wood, coals, or
other fuel, raised to a certain temperature.
• Potential Calcination
o Potential calcination is that brought about by potential fire, such as corrosive
chemicals; for example, gold was calcined in a reverberatory furnace with
mercury and sal ammoniac; silver with common salt and alkali salt; copper
with salt and sulfur.

Calcination Reaction:
• Calcination reactions usually take place at the thermal decomposition temperature (for
decomposition).
• For example: In limestone calcination, a decomposition process, the chemical reaction
is

CaCO3 → CaO + CO2 (g)

Apparatus:
• Shaft furnaces
• Calcining kilns
• Multiple hearth furnaces
• Fluidized bed reactors

1. SHAFT FURNACES:
• A vertical, refractory-lined cylinder in which a fixed bed (or descending column) of
solids is maintained, and through which an ascending stream of hot gas is forced.

2. CALCINING KILNS:
• This process is done in kilns.
• Calcining kilns basically comes in two categories.
2.1. Rotary Kilns:

• Rotary kilns can be long kilns with rotatory coolers while verticals kilns can be several
types. Calcining kilns need lime stone with decrepitation index.
• Decrepitation index of limestone is a measure of its susceptibility to disintegrate
during calcination.
• Low value of decrepitation decreases the porosity of the lime thus impeding the flow
of the gases and reducing the kiln efficiency.
• The smaller size limestone is more suitable for calcination in rotary kilns.

2.2. Vertical Kilns:

• A kiln consisting of a steel shell with a vertical axis and a lining of firebrick.
• The most popular vertical kilns are PFR (Parallel Flow Regenerative) type.

3. MULTIPLE HEARTH FURNACE:

• For the decomposition of limestone, a large number of heat is requiring as we know
calcination is an endothermic process and it is done on industrial scale. This is done by
multiple hearth furnaces.

4. FLUIDIZED BED REACTORS:

• A fluidized bed reactor (FBR) is a type of reactor device that can be used to carry out
a variety of multiphase chemical reactions. In this type of reactor, a fluid (gas or
liquid) is passed through a granular solid material at high enough velocities to suspend
the solid and cause it to behave as though it were a fluid. This process, known as
fluidization.

Process:
• Calcination (also referred to as Calcining) is a thermal treatment process in presence
of air or oxygen applied to ores and other solid materials to bring about a thermal
decomposition.
 • Calcination of calcium carbonate is a highly endothermic reaction, requiring 755 M
Cal of heat input to produce a ton of lime. The reaction begins when the temperature is
above the dissociation temperature of the carbonates in the limestone.
• Once the reaction starts the temperature must be maintained above the dissociation
temperature, and carbon dioxide evolved in the reaction must be removed.
Dissociation of the calcium carbonate proceeds gradually from the outer surface of the
particle inward, and a porous layer of calcium oxide, the desired product, remains.

High Temperature:
• This calcination means higher agglomeration and more shrinkage. At this limestone
becomes so dense during calcination that it prevents the escape of CO 2 and becomes
non porous. The internal pressure of limestone increases and it explodes, producing
unwanted materials and reduces the quality of lime.
• Increasing the degree of calcination beyond the limited temperature makes formed
lime crystallites to grow larger, agglomerate. This results in a decrease in porosity and
reactivity and an increase in bulk density. This product is known as Dead burnt or
Low reactive lime.

Low Temperature:
• This calcination allows less fuel consumption.
• At relatively low calcination temperatures, products formed in the kiln contain both
unburnt carbonate and lime and is called ‘under burnt’ lime. As the temperature
increases ‘Soft burnt’ or ‘high reactive lime’ is produced. At still higher temperature,
`dead burnt` or low reactive lime is produced.
• Soft burnt lime is produced when the reaction front reaches the core of the charged
limestone and converts all carbonate present to lime. Such lime has the optimum
properties of high reactivity, high surface area and low bulk density.
• The production of good quality lime depends upon the type of kiln, conditions of
calcination and the nature of the raw material i.e. limestone.
Applications:
• Calcination is used in the preparation of certain inorganic substances such as calcium
oxide, light magnesium oxide, heavy magnesium oxide, zinc oxide and red mercuric
oxide.
• These substances are prepared by heating their respective carbonates.
• It is used to remove water of crystallization as water vapors.
• Most of the mined magnesite is converted directly into magnesium oxide(magnesia)
by burning (calcining).

MgCO3 → MgO + CO2

ADSORPTION
Introduction:
• It is a surface phenomenon and refers to the uniform distribution of a substance
through another at the surface.
• It is the phenomenon in which a layer of ions, molecules or aggregates of molecules
condense upon the surface with which they come in contact.

Importance:
The term surface is customarily used when referring to a gas / solid or a gas / liquid
interface. This phenomenon is a significant factor as:

• Adjuncts in dosage forms

• Penetration of molecules through biological membranes
• Emulsion formation
• Stability and the dispersion of insoluble particles in liquid media to form suspension

Adsorption:
It is an accumulation of substance at the interface or boundary between two and
heterogeneous phases. For example, Solid-Gas, Oil- H2O, Gas-Liquid, or Solid-Liquid.

Absorption:
It implies the penetration one component throughout the body of a second. The
distinction between adsorption and absorption is not always clear.
Components of Adsorption:
Adsorption consists of two components:

• ADSORBENT: Adsorbant is the substance which adsorbs the other substance at its
surface. E.g. Kaolin, pectin, altpulgite, talc, Magnisum trisilicate, Al(OH) 3,
Simithicone, CaCO3 (Activated Charcoal), Mg(OH) 3 etc.
• ADSORBATE: Adsorbate is the substance which is adsorbs on the other substance’s.
E.g. Toxins, Strychnine HCl, Digoxin and many other drugs

Example:
• Stychinine HCl onto Activated Charcoal (Solid – Liquid)
• Activated Charcoal used in Respirators for civilian and forces (Solid- Gas)
• Decrease in surface tension is due to surface active agent for example liquid-gas
bonding.
• Emulsifying agent as emulsion stabilizers in case of liquid- liquid bonding.

Factor Affecting Adsorption:

• Solubility of adsorbate
• Nature of Adsorbate
• Nature of adsorbent
• Surface area of absorbant
• Affinity between adsorbent and adsorbate
• Concentration of both adsorbate and adsorbent
• Pressure
• Temperature
• pH

Types of Adsorbents:
• Oxygen containing compounds
o Typically, hydrophilic and polar
o E.g. silica gel, zeolites
• Carbon based compounds
o Typically, hydrophobic and non-polar
o E.g. activated carbon, graphite
• Polymer based compounds
 o Polar or Non polar functional groups in a porous polymer matrix
o Examples: Polymers & Resins

Classification of Adsorbents Based on Pore Size:

• Microporous Adsorbents
o Pore Size Range - 2 Aº to 20 Aº
• Mesoporous Adsorbents
o Pore Size Range - 20 Aº to 500 Aº
• Macroporous Adsorbents
o Pore Size Range - > 500 Aº

Commercial Adsorbents:
• SILICA GEL
o Drying of refrigerants, organic solvents, transformer oils
o Desiccants in packing & double glazing
o Dew Point Control of natural Gas
• ACTIVATED ALUMINA
o Drying of gases, organic solvents, transformer oils
o Removal of HCl from Hydrogen
o Removal of fluorine in alkylation process
• ACTIVATED CARBON
o Removal of odors from gases
o Recovery of solvent vapours
o Nitrogen from air
o Water purification
o Purification of He
• POLYMERS & RESINS
o Water Purification
o Recovery & purification of steroids & amino acids
o Separation of fatty acids from water & toulene
o Recovery of proteins & enzymes
• CLAY
o Treatment of edible oils
o Removal of organic pigments
o Refining of mineral oils
o Removal of poly chlorinated biphenyls (PCBs)
• ZEOLITES
o Oxygen from air
o Drying of gases
o Drying of refrigerants & organic liquids
o Pollution control including removal of Hg
o Recovery of fructose from Corn Syrup

Application of Adsorption:
 Adsorption has the application in:
1. Preparative and Analytical Chromatography
2. Heterogeneous catalysis
3. Water purification
4. Solvent recovery

Medical and Pharmaceutical Applications:

1. ADSORPTION OF NOXIOUS SUBSTANCE FROM ALIMENTARY CANAL:
Universal and antidote (activated charcoal, MgO and Tannic acid) when used orally, reduces
toxic levels of poisoning.
2. REMOVAL OF TOXIC ELEMENTS FROM BLOOD: Some adsorbents are used to
remove toxic elements by subjecting its dialysis through “hemodialysis” membrane over
charcoal and adsorbents (chlorpheniramine, colchicine, Phenytoin, aspirin etc.)
3. TREATMENT OF SEVERE DRUG OVERDOSES:

• Extracorporeal method has been developed named “Haemoperfusion”.

• Microencapsulation of activated charcoal by Arcylic Hydrogel, a biocompatible
material preventing Embolism and removal of platelets.
• In vivo – In vitro relationship regarding adsorptive capacity of adsorbents.
• No relationship exists.
• Reason:
o GIT and biological system have many other things which alter the adsorption
ratio.
• Example:
o In vitro – 5g activated charcoal bin 8g of Aspirin
o In vivo – 30g of activated charcoal inhibits the GIT adsorption of 3g of Aspirin
by 50%.

4. ADSORPTION PROBLEMS IN DRUG FORMULATION: Drugs containing antacids

and other drugs, when given, the above problem results. Adsorbents are non-specific
nutrients, drugs and enzymes when given orally. Example: promazine given above or
adsorbents.
 DECANTATION
Introduction:
Decantation is a process by which a liquid is separated from a solid. The solid is
allowed to settle and liquid is poured off carefully leaving the settled solid undisturbed.

Definition:
• “Decantation is a process for the separation of mixtures, by removing a layer of liquid,
generally one from which a precipitate has settled”.
• Decanting is a process to separate mixtures. Decanting is just allowing a mixture
of solid and liquid or two immiscible liquids to settle and separate by gravity.
• This process can be slow and tedious without the aid of a centrifuge. Once the mixture
components have separated, the lighter liquid is poured off leaving the heavier liquid
or solid behind.
• Decantation is a process to separate mixtures by removing a liquid layer that is free of
a precipitate, or the solids deposited from a solution. The purpose may be to obtain a
decant (liquid free from particulates) or to recover the precipitate.

Process:
• In laboratory conditions, small volumes of mixtures are decanted in test tubes. If time
is not a concern, the test tube is kept at a 45° angle in a test tube rack.
• This allows the heavier particles to slide down the side of the test tube while allowing
the lighter liquid a path to rise to the top. If the test tube were held vertically, the
heavier mixture component could block the test tube and not allow the lighter liquid to
pass as it rises.

Purpose / Aim:
 • The purpose of decantation is to separate insoluble liquids from solids.
• The purpose may be either to produce a clean decant, or to remove undesired liquid
from the precipitate (or other layers).
• DECANTER: A decanter is a vessel used to hold the decantation of a liquid which
may contains sediments.

Principles:
The principles of decantation are:

• Sedimentation
• Centrifugation

Decantation is a “pouring off” of a liquid from a solid/liquid mixture. The mixture is

allowed to settle, and the liquid is removed while preventing the solid from escaping.

When it is used?
Decantation is used when one is separating part of a mixture from another and when the
particles or sediments are too fine to be filtered from a liquid.

Procedure:
The steps of decantation are given below:
1. Mixture in the container is allowed to stand for sometime
2. The solid particles will settle in time
3. The upper layer of the liquid gets cleaner
4. Separate the course particles of a solid from a liquid by pouring the liquid to a new
container by the process of decantation

Examples:
1. Oil & Water: Oil floats on the top of the water. Decanting the mixture allows the oil
to be poured off the water.
 2. Dirt and water: Muddy water can be cleared up by decanting. The soil will sink to
the bottom of the tube allowing the clear water to be poured off.
3. Cream & Milk: Cream is separated from milk by decantation. Cream rises to the top
of the milk mixture and easily skimmed off.
4. Blood & plasma: A centrifuge is necessary for this decantation. Plasma can be
removed from the blood by decantation.

Disadvantages:
• It cannot be used to separate a mixture of a liquid and a light solid, such as chalk in
water. The particles of chalk are suspended I the water. They are so light that they do
not sink down to the bottom for a long time.

Applications:
1. It is employed in washing precipitates by adding the wash solution, allowing the solid
to settle, and pouring off, continuing the process until free from impurities. If the solid
to be separated settles rather rapidly, decantation may be employed to the advantage.
2. In order to separate an insoluble solid from a liquid.

EVAPORATION
Definition:
• Evaporation is a type of vaporization of a liquid that occurs only on the surface of a
liquid.
• The other type of vaporization is boiling, which instead occurs on the entire mass of
the liquid.

Introduction:
• Theoretically evaporation means free escape of vapours from the surface of a liquid
below its boiling point.
 • As evaporation is a very slow process, therefore a liquid is usually boiled / heated to
speed up this process.
• So, practically evaporation may be defined as the removal of liquid from a solution, by
boiling the solution in a suitable vessel from where the vapors are withdrawn and a
concentrated liquid is left behind.
• The Evaporation is maximum at the boiling point of a substance.
• For molecules of a liquid to evaporate, they must:
o Be located near the surface
o Be moving in the proper direction
o Have sufficient kinetic energy to overcome liquid-phase intermolecular forces
• Only a small proportion of the molecules meet these criteria, so the rate of evaporation
is limited.
• Since the kinetic energy of a molecule is proportional to its temperature, evaporation
proceeds more quickly at higher temperatures.
• As the faster-moving molecules escape, the remaining molecules have lower average
kinetic energy, and the temperature of the liquid, thus, decreases.

Factors Effecting Evaporation:

• Temperature
• Surface Area
• Agitation
• Atmospheric Aq Vapor Pressure
• Type of Product required
• Economic Factors

1. Temperature:
The rate of evaporation is directly proportional to the temperature. The higher the
temperature, the higher will be evaporation but evaporation is maximum at the boiling point
of the liquid.
2. Surface Area:
The rate of evaporation is directly proportional to the surface area of the vessel
exposed to evaporation. Greater the surface exposed to evaporation, the higher will be the rate
of evaporation.
3. Agitation:
During evaporation a layer or scum is formed at the surface. Therefore it is necessary
to agitate and stir the solution during evaporation. Agitation also increases the rate of
evaporation.
4. Atmospheric Aqueous Vapor Pressure:
If atmospheric moisture contents in air are high, rate of evaporation will be slow but if
less then evaporation will be fast. Rate of evaporation can be increased by circulation of warm
air over the evaporating pan.
5. Atmospheric Pressure:
Rate of evaporation is inversely proportional to the atmospheric pressure on the
surface of the liquid. Rate of evaporation become doubled by reducing the atmospheric
pressure on the liquid to one half. Due to this reason, in many cases evaporation is done under
reduced pressure.
6. Type of the Product Required:
Selection of method and apparatus depends on the type of the product required.
7. Economic Factors:
They contribute significantly in selecting the method and the type of apparatus to be
used for evaporation.

Types of Evaporators:
1. Small Scale Evaporators
2. Large Scale Methods
a) Evaporating Pans
b) Evaporating Stills

1. SMALL SCALE EVAPORATORS (LAB SCALE):

• Small quantity of liquids may be evaporated in porcelain or glass dish.
• Direct heat by Bunsen burner or electric hot plate may be applied, but direct heat leads
to decomposition of the substances towards the end of the evaporation
• A fixed maximum temperature can easily be attained by employing different types of
baths as a source of indirect heating
• Water bath is most suitable when liquids are to be heated up to 100ºC. These are
simple and cheap
• Sand bath or oil bath containing liquid paraffin or soft paraffin may be used when
higher temperatures upto 300ºC are required.
• Glycerin bath is used to attain a temperature upto 150ºC
• To prevent decomposition, whole of the liquid should not be evaporated to dryness;
instead the last traces of the solvent from the concentrated liquid should be removed
under controlled temperature.
• In case of large quantities of liquids or solutions having costly solvents, the
evaporation should be carried out by distillation under reduced pressure.

2. LARGE SCALE METHODS:

A. Evaporating Pans:

• On large scale, liquid extracts containing water as a menstruum are evaporated in large
open pans called evaporating pans.
• They consist of hemispherical or shallow pans, made of copper, stainless steel,
aluminum, enameled iron or other metal and surrounded by a steam jacket.
 • The hemispherical shape is most suitable because it gives the best surface/volume
ratio for heating and the largest area for disengagement of vapours.
• The pans may be fixed, or have a mounting, permitting it to be tilted to remove the
product.

Advantages:
a) They are simple, easy and cheap to construct.
b) Easy to use, clean and maintain.
c) Stirring of the evaporating liquid can easily be done.

Disadvantages:
a) On the evaporating surface a scum is rapidly formed which decreases rate of
evaporation.
b) Solids may be deposited at the bottom, which makes stirring necessary.
c) Cannot be used for extracts containing organic solvents like alcohol etc.
d) The rooms, in which the evaporating pans are used, must have an efficient exhaust
system. Otherwise the room will be filled with dense fog of condensed vapors and
water will start falling from the roof and along the sides of the wall

B. Evaporating Stills:
• These are similar to pans, and consist of a vessel made of copper or stainless steel.
• They are used in large scale pharmaceutical manufacturing

Applications of Evaporation:
1. One of the most important methods in manufacture of pharmaceuticals.
2. Used for preparation of different type of extracts.
3. In the manufacture of drugs containing antibiotics, hormones, enzymes etc.
 VAPORIZATION
Introduction:
• Vaporization of an element or compound is a phase transition from the liquid to gas
phase
• There are two types of vaporization:
o Evaporation
o Boiling
• Evaporation is a phase transition from the liquid phase to gas phase that occurs at
temperatures below the boiling temperature at a given pressure.
• Evaporation usually occurs on the surface.
• Boiling is a phase transition from the liquid phase to gas phase that occurs at or above
the boiling temperature.
• Boiling, as opposed to evaporation, does not occur only at the surface.
• Sublimation on the other hand is a direct phase transition from the solid phase to the
gas phase, skipping the intermediate liquid phase.
• Heat must be supplied to a solid or liquid to effect vaporization.
• If the surroundings do not supply enough heat, it may come from the system itself as a
reduction in temperature.
• The atoms or molecules of a liquid are held together by cohesive forces, and these
forces must be overcome in separating the atoms or molecules to form the vapour.
• The heat of vaporization is a direct measure of these cohesive forces
• Condensation of a vapour to form a liquid or a solid is the reverse of vaporization
• In condensation heat must be transferred from the condensing vapour to the
surroundings. The amount of this heat is the same as the heat of vaporization.

Applications:
• Coating of Tablets
• Control of Moisture Content of Powders
• Drying of wet granules, to be used in compression of tablets

CENTRIFUGATION
It is the process that involves the use of centrifugal force for the separation of two
immiscible liquids or separation of solid from liquids.

Principle:
The centrifuge works using the sedimentation principle, where the centripetal
acceleration causes denser substances and particles to move outward in the radial direction. At
the same time, objects that are less dense are displaced and move to the center.
Process:
This process is used to separate two miscible substances, but also to analyze
the hydrodynamic properties of macromolecules. More-dense components of the mixture
migrate away from the axis of the centrifuge, while less-dense components of the mixture
migrate towards the axis. Chemists and biologists may increase the effective gravitational
force on a test tube so as to more rapidly and completely cause the precipitate (pellet) to
gather on the bottom of the tube. The remaining solution (supernatant) may be discarded with
a pipette.

Unit:
Rev/min

Factors Affecting:
The particle setting velocity in centrifugation is in function of following things.

• Centrifugation acceleration
• Volume fraction of solids
• Density difference between solids and liquids
• Viscosity of liquids

Applications:
• It is used in the purification of oil.
• It is used to purify enzymes.
• Blood plasma is separated from blood cells by centrifugation.
• Other organic and inorganic compounds are purified by this method.
• It is used in separating the chalk powder from water.
• It is used to removing fat from milk to produce skimmed milk.
• It is used in drug manufacturing and processes.
• Used in the sugar industry to separate the sugar crystals from the mother liquor.
• Pharmaceutically used for:
o Determination of molecular weight of colloids.
o Evaluation of suspensions and emulsions.
o Production of biological products.
o Production of bulk drugs.
o Determination of blood components
 DESICCATION
Definition:
• The word desiccation is derived from Latin word “desiccare” means to dry
completely.
• The process of desiccating a thing is called desiccation.
• Desiccation is a dehydration process for removing moisture from solid or liquid
substances.
• The moisture thus driven off is called hygroscopic moisture as distinguished from
moisture that is chemically combined as in water of crystallization.

General Introduction:
• Desiccation is the state of extreme dryness, or the process of extreme drying.
• A desiccant is a hygroscopic substance that induces or sustains such a state (Dryness)
in its local vicinity, in a moderately sealed container.
• A desiccator is a heavy glass or plastic container used for making or keeping small
amounts of material very dry.
• The material is placed on a shelf, and a drying agent or desiccant, such as dry silica
gel or anhydrous sodium hydroxide, is placed below the shelf.
• Desiccation is the process of removing adhered moisture from liquid or solid
substances.
• The term desiccated is used for those substances from which the water or moisture has
been completely removed.

Purpose:
• To remove the moisture from a thing that normally contains moisture, such as plant; to
dry out completely; to preserve by drying.
• Manufacture of dietary supplements and medicines desiccate some product to extend
their shelf life and maintain purity.
• The object of the process is to preserve medicinal value of the substance.
• To reduce the bulk and weight and facilitate powdering of chemicals and crude drug.

Process:
• On small scale, desiccation can be carried out in a desiccator which consists of a
tightly closed glass or plastic vessel, containing a drying agent at its bottom, which
absorbs the moisture from the substance being desiccated.
 • Commonly used desiccants are, conc. Sulphuric acid, phosphorus pentoxide,
exsiccated (anhydrous), phosphoric anhydride, calcium chloride and silica gel.
• The drug or substance to be dried is taken in a china dish and placed inside the
desiccator above the surface of drying agent.
• For continuous operation the desiccator may sometimes be connected to a vacuum
pump.
• The moisture sensitive substances formulated in tablets and capsules are protected by
enclosing them in sealed vials, on bottom of which a small cloth bag containing silica
gel is placed which acts as a desiccant.
• In case of organic solvents, the traces of moisture are removed by passing them
through a column of alumina or silica gel.

Examples:
• Desiccated beef liver is a dietary supplement marketed in the form of powders and
tablets.
• Synthetic desiccated thyroid hormone is a medicine marketed in the form of pills to
treat thyroid conditions such as myxedema, which can cause drowsiness, tissue
swelling, tongue enlargement and other symptoms because of insufficient hormone
output by the thyroid gland.

Applications:
• In preservation of vegetable and animal drugs that are destroyed in presence of
moisture.
o Dry drug contains 12% moisture
o Desiccant drugs contain 0% moisture
• Comminution of drugs is difficult when they are wet, but it becomes easy when they
are dried.
• To decrease the bulk and weight of substances containing moisture to facilitate their
easy handling.
• To increase shelf life of drugs
• To increase the stability of drugs
• To avoid hydrolysis, oxidation etc.
• To keep the compound intact
• Pharmaceutical companies often use freeze drying as a desiccation tool to increase the
shelf life of product
• Microorganism cannot grow and divide when desiccated, but can survive for certain
period of time, depending medicine and facilitate powdering
• Reduced bulk weight of and facilitate powdering
 LEVIGATION (Wet Grinding)
General Introduction:
• The process of particle size reduction by first forming a paste of solid by adding the
minimum amount of suitable non-solvent (levigating agent) and then triturating the
paste in the mortar or on the slab by using the pestle or spatula.
• Levigation is commonly used in small scale preparation of ointments to reduce the
particle size and grittiness of the added powders.
• A mortar and pestle or an ointment tile is used for this purpose.
• A paste is formed by combining the powder and a small amount of liquid (the
levigating agent) in which the powder is insoluble
• The paste is then triturated in the mortar by the pestle or on the ointment tile by a
spatula to reduce the particle size.
• The levigated paste is then added to the ointment base and the mixture is made
uniform and smooth by rubbing it together with a spatula on the ointment tile.
• The most common levigating agents are mineral oil, water, alcohol and glycerin.
• The process of levigation is also known as wet grinding and is used to reduce the
particle size of a substance to finer state of subdivision
• This process is often used to incorporate solid substances into dermatological and
ophthalmic ointments and suspensions.

Applications:
• Size reduction
• Preparation of ointments and pastes.
• Commonly used levigating agents are mineral oil and glycerin.
• This process is used in making suspensions.

TRITURATION
Introduction:
• It is also called as dry grinding.
• Trituration may be used both to comminute and to mix powders.
• By trituration the grinding of a solid substance is done to fine powder by continuous
striking or rubbing the particles in a mortar with a pestle.
• If simple admixture is required without special need for comminution, the glass mortar
is usually preferred.
• When a small amount of a potent substance is to be mixed with a large amount of
diluent, geometric dilution method is used to ensure the uniform distribution of the
potent drug.
• This method is specially indicated when the potent and other ingredients are of the
same color and a visible sign of mixing is lacking. By this method the potent drug is
placed on an approximately equal volume of the diluent in the mortar and mixed
 thoroughly by trituration. Then a second portion of diluent equal in volume to the
mixture is added and the trituration repeated and so on. This process is repeated until
all the diluent is incorporated.

Trituration Using Tile and Spatula:

• Small quantities of finely powdered solids may be mixed on a tile by means of a
spatula.
• Tiles are usually made of glass and should be large enough for the quantity of powder
to be mixed or ointment to be prepared.
• Usually for small scale work 300mm square is a useful size for a tile.
• Spatula is made of stainless steel except for the few medicaments those react with
stainless steel (iodine), should be flexible and long blade (25mm by200mm) to provide
a large rubbing surface.
• Powders for Trituration are placed on the tile and gently mixed until the mixture is
smooth and homogeneous, but in the case of ointment if base is very soft it may be
helpful to warm the tile but overheating should be avoided because the base will
become too fluid for efficient levigation and may run off the edge of the tile. The
dispersion is then diluted with increasing amount of base, doubling the quantity each
on the tile of each dilution. Finally, any liquid ingredient is incorporated.

Trituration Using Mortar and Pestle:

• A mortar should be used when the quantities are too large to be conveniently dealt
with tile.
• A mortar with a fairly flat base and a pestle with a flat head will give best results.
• It is impossible to ensure intimate dispersion of one powder in another by mixing the
two substances all at once. The purpose is to add a substance that is present in greater
amount to the whole of the substance present in lesser amount.
• Substance present in greater amount is introduced into the mixture in very small
quantities at first, but gradually increasing the quantities, until the whole of the
substance has been added. In the case of ointments, the sequence of mixing is same as
in the tile method, powders are mixed and then gradually incorporated into the base
and finally any liquid ingredients are added.

Applications:
• Size reduction.
• Geometric mixing of powders.