Miscellaneous Processes
Evaporation Sublimation Exsiccation Desiccation Fusion
Calcination Ignition Lyophilization Efflorescence Deliquescence
Decantation Centrifugation Levigation Elutriation Trituration
Evaporation
Theoretically evaporation means the free escape of vapours
from the surface of a liquid below its boiling point. It's a slow
process and can take place even at room temperature since
evaporation is too slow at room temperature, so the liquid is
boiled from where the vapours escape in the form of bubbles
from the bulk of the liquid.
The evaporation may be defined as the removal of liquid
from a solution by boiling the solution in a suitable vessel
from where the vapours are withdrawn, and a concentrated
liquid is left behind. Evaporation is maximum at boiling point
of the substance.
Evaporation differs from boiling that evaporation takes place
at all temperatures whereas boiling takes place only at one
temperature at a given pressure. Evaporation occurs only at
the surface of the liquid whereas in case of boiling, vapours
formation takes place from whole of the liquid.
Boiling occurs when the vapor pressure of the liquid becomes
equal to atmospheric pressure. Evaporation differs from
distillation that in evaporation the solvent which is generally
water is not condensed and collected whereas in distillation
the solvent vapours are condensed and are collected in a
receiver.
Sublimation
• Sublimation is the transition from the solid phase to the gas phase without
passing through an intermediate liquid phase. This endothermic phase
transition occurs at temperatures and pressures below the triple point.
• Triple point: In thermodynamics, the triple point of a substance is the
temperature and pressure at which the three phases (gas, liquid, and solid)
of that substance coexist in thermodynamic equilibrium.
• The term "sublimation" only applies to physical changes of state and not to
the transformation of a solid into a gas during a chemical reaction.
• The opposite process of sublimation—where a gas undergoes
a phase change into solid form—is called deposition or desublimation.
Applications of sublimation
In certain cases, to prevent the decomposition of substances due to high temperature sublimation can be done
at low temperatures under reduced pressure
The process of sublimation is used in the purification of many pharmaceutical substances such as Iodine
camphor , Mercuric chloride, mercurous chloride and sublimed Sulphur.
It is also used in the manufacture of Iodine, ammonium chloride and naphthalene.
This process is also employed to purify volatile solids contaminated with non-volatile impurities.
Exsiccation
• Exsiccation is the process of removing the water of crystallization from the hydrated crystalline
substances and making them anhydrous.
• Examples of exsiccated substances include exsiccated ferrous sulphate, exsiccated magnesium,
sulfate exsiccated, sodium sulfate, exsiccated sodium carbonate, exsiccated alum and anhydrous
sodium arsenate.
• In the laboratory exsiccation may be carried out by taking a weighed amount of the substance in
a tared dish which is heated on water bath, sand bath or in oven, with continuous stirring until a
constant weight is obtained or until the calculated loss in weight has taken place.
• The temperature required to remove water of crystallization is very important for example
copper sulfate CuSO4. 5H2O, when heated at about 30 C° losses two molecules of water of
crystallization, at 100 C° it loses two more water molecule, and the last water molecule is
removed when it is heated at 200 C° thus forming CuSO4.
Exsiccation is done to get an anhydrous product required in the
formulation of certain medicaments.
Applications of It is also carried out to reduce the bulk and weight of certain drugs so
that they can be easily administered.
Exsiccation
Generally, on exsiccation a fine powder of substance is obtained. Since
the exsiccated salts are very hygroscopic, so must be stored in well
closed containers.
Desiccation
Desiccation is the process of removing adhered moisture from liquid or solid substances.
The term desiccated should be used for those substances from which water has been completely removed.
On laboratory scale desiccation can be carried out in a desiccator which consists of a tightly closed glass vessel containing a drying agent at its
bottom which absorbs moisture from the substance being desiccated.
the commonly used drying agents include concentrated sulfuric acid, phosphorous pentoxide, exsiccated calcium chloride and silica gel.
The drug to be dried is taken in a dish which is placed inside the desiccator above the surface of it drying agent for continuous operation the
desiccator may sometime be connected to a vacuum pump.
Desiccator
Desiccation
Applications
• The substances which are very sensitive to moisture
Desiccation helps in preserving
the vegetable and animal drugs
which get destroyed in the
are formulated as tablets or capsules which are presence of moisture.
further protected by enclosing them in sealed vials on
the bottom of which is small cloth bag containing
silica gel is placed which acts as a desiccant. comminution of drug
Stability of is difficult if they are
certain drug is wet but if they are
also increased. dry can be easily
• The last traces of moisture from some of the organic
powdered.
solvents is removed by passing through a column of
alumina or silica gel. Desiccation reduces the bulk and
weight of the substance due to
the loss of adhering moisture in
them therefore they become easy
to handle.
Fusion
• Fusion is the process by which the solids gets converted into liquids without adding
any solvent.
• It may also be defined as the process of heating the solids until they melt.
• Fusion is done to purify certain solids and semisolid substances such as beeswax, hard
paraffin, soft paraffin and wool fat are heated to melt and filtered while hot to remove
the dissolved impurities.
• On cooling, a product free from dissolved impurities is obtained. This method is also
applied for the preparation of ointments when they also contain solids and semi solids
in the formulation.
• All the substances are melted and then cooled slowly with continuous stirring until a
uniform product is obtained.
• To avoid overheating substances with higher melting points are melted first to which
substances with lower melting points are added.
Calcination
Calcination, which refers to the heating of inorganic materials to remove volatile components under controlled temperature and in a
controlled environment. Usually, heating is done in the absence of air or oxygen.
Calcination is done to bring about some change in the substance physical or chemical constitution.
During calcination, solids are heated at high temperatures. This is done to mainly remove volatile substances, water or oxidize the
substance. This process is also sometimes described as a purification process. The word Calcination has also been derived from the
Latin word “Calcinare” which translates as “to burn lime”.
A typical calcination process involves the conversion of calcium carbonate to calcium oxide.
ΔH
CaCO3 𝐶𝑎𝑂 + 𝐶𝑂2
Calcination
The main purpose of calcination of ores are to convert carbonates and hydroxides ores • Purpose
into oxides. • Remove the volatile impurities
• To remove moisture
• ZnCO3 → ZnO + CO2 • Make the mass porous
• In the figure, the fire burns on the grate at G. Now the
flames passing over the bridge at E are deflected
• CaCO3 → CaO + CO2 downward by the low sloping roof of the furnace and pass
directly over the surface of the charge or the material
under calcination which is laid on the platform B. The
• 2Al(OH)3 → Al2O3 + 3H2O
fumes and hot gases then escape through the throat F into
the chimney. The charge is spread out evenly on the bed as
• On Laboratory scale, calcination is done in silica or platinum crucibles whereas in
a thin layer.
industries metallic vessels are used. Preparations of certain inorganic substances
such as calcium oxide, light magnesium oxide, heavy magnesium oxide, zinc oxide
& red mercuric oxide. These substances are prepared by heating their respective
carbonates.
• Ignition or incineration is the process by which an organic substance is strongly heated until whole
of carbonaceous matter burns and in inorganic residue know as ash is left behind.
Ignition • On laboratory scale ignition is carried out in silica or platinum crucibles.
• This process is mainly used for the standardization of organic substances and crude by means of
gravimetric analysis.
• The sulfated ash test uses a procedure to measure the amount of residual substance not volatilized
from a sample when the sample is ignited in the presence of sulfuric acid. The test is usually used
for determining the content of inorganic impurities in an organic substance
Lyophilization/ Freeze
drying
• Freeze drying, which is also known as lyophilization, is the process of
removing water from a product by freezing it then subliming the ice
to vapor.
• Sublimation is a physical phenomenon by which solid ice is
converted directly into vapor without it passing through the liquid
state.
• Removing water from drugs, by sublimation, protects the material
against loss of important constituents and against chemical reactions
that are associated with withdrawing or vaporizing liquid water.
Lyophilization consists of three
interconnected stages:
Freezing: During this step, the water or solvent in a product is gradually frozen by cooled shelves. This creates ice crystals that are
separated from the drug product and more easily removed by sublimation.
Primary Drying (Sublimation): During this step, pressure is manipulated to convert water directly from solid to gas via sublimation, and
the resulting water vapor is collected on a condenser.
Secondary Drying (Desorption): During this step, the shelf temperature in the lyophilizer is gradually raised under low pressure to drive
off residual water or solvent. Careful consideration is given to ensure the temperature doesn’t exceed values at which product
components are degraded or changed (this is especially important for thermally sensitive products like biologics)
Applications of Lyophilization
Freeze drying, or lyophilization, is a stabilization
Freeze-dried products have a very high surface
method that is widely used in the pharmaceutical
area, which enables them to be reconstituted
industry for drugs, vaccines, antibodies, and other
quickly. This quick reconstitution is particularly
biological material. Because the product is dried
important in the case of emergency vaccines and
without excessive heating, proteins and other
antibodies, which need to be administered as soon
products that would be thermally denatured can
as possible.
be successfully preserved without loss of activity.
Efflorescence
▪ The large no of chemical compound exists in hydrated or anhydrous form. In hydrated form the water
molecule attached to the compound are called the water of crystallization. The surrounding atmosphere also
has vapours and definite vapour pressure, due to water in atmosphere.
▪ Efflorescence, spontaneous loss of water by a hydrated salt, which occurs when the aqueous vapor pressure of
the hydrate is greater than the partial pressure of the water vapour in the air.
▪ For example, because the vapour pressures of sodium carbonate (Na2CO3·10H2O) and sodium sulphate
(Na2SO4·10H2O) normally exceed that of the water vapour 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 copper sulfate, (CuSO4·5H2O), the aqueous vapour pressure of which is lower, undergoes
efflorescence only if the air in contact with it is relatively dry.
Efflorescence or loss of water of
crystallization can be prevented by the
following ways:
Prevention of
Efflorescence • By closing the container immediately after use.
• By filling the container completely so that no space for
air storage is available above the liquid in the container.
Deliquescence
• The process by which a substance absorbs moisture from
the atmosphere until it dissolves in the absorbed water and
forms a solution.
• Deliquescence occurs when the vapour pressure of the
solution that is formed is less than the partial pressure of
water vapour in the air.
• Example, solid NaOH, CaCl2, CaCl2. 6H2O, P4O10 (forms
HPO3), FeCl3, KOH, MgCl2.
By closing the container immediately after using it.
Prevention of By filling the container completely so that no space for air
storage is available above the liquid in the container.
Deliquescence
By placing the dehydrating agent e.g: (Silica gel)to absorb
water.
Hygroscopy/Hygroscopic
• This is when substances absorb water from air,
but not enough to form solutions
• Examples of such substances include CaO,
NaNO3, NaCl, Sucrose and CuO. Also, certain
liquid substances absorb water from the air to
get diluted - these are also regarded as being
hygroscopic. Example, conc. H2SO4 and conc.
HCl.
• If a hygroscopic substance absorbs so much
moisture that an aqueous solution is formed, the
substance becomes deliquescent.
Decantation
Definition: Decantation is the process of separation of liquid from solid and other immiscible
(non-mixing) liquids, by removing the liquid layer at the top from the layer of solid or liquid
below.
The process can be carried out by tilting the mixture after pouring out the top layer. This
process can also be used to separate two liquids that do not mix with each other for e.g., oil
and water.
When we leave the mixture of oil and water, two separate layers are formed, with water at the
bottom and oil, being lighter, at the top. We can remove the oil layer from the top by pouring
it into another vessel, which leaves us with the water layer at the bottom.
Centrifugation
• Definition: Centrifugation is a technique used for the separation of
particles by spinning them in solution around an axis (in a
centrifuge rotor) at high speed from a solution according to their
size, shape, density, viscosity of the medium and rotor speed.
• It is one of the most useful and frequently employed techniques in
the molecular biology laboratory.
• Centrifugation is used to collect cells, to precipitate DNA, to
purify virus particles, and to distinguish subtle differences in the
conformation of molecules.
• There are two types of centrifuge procedures; one is preparative,
the purpose of which is to isolate specific particles, and the other is
analytical, which involves measuring physical properties of the
sedimenting particles.
Trituration
• Trituration is also the name of the process for reducing
the particle size of a substance by grinding. As an
example, trituration can refer to the grinding of
powders in a mortar with a pestle.
• Or
• Trituration is also the production of a homogeneous
material through mixing. For example, dental
amalgam is formed by combining particles of an alloy
with mercury.
• PURPOSE OF LEVIGATION
Levigation • It is used to prepare the ointments and pastes.
• In making suspensions.
• Definition: Levigation is a process of reducing the • In many pharmaceutical balms.
particle size of a solid by triturating it in a mortar
• In purification of drugs.
or spatulating it on an ointment slab or pad with a
small amount of a liquid or melted base in which • To get various degrees of fine powders.
the solid is not soluble.
• The liquid used for Levigation is called as
‘levigation agent', The liquid is somewhat viscous
and has low surface tension to improve ease of
wetting the solid. e.g.: Mineral Oils, Glycerin.
Levigation is wet grinding while trituration is dry grinding.
Levigation Vs Triturate is the continual rubbing of a solid in a mortar with a
Trituration pestle to reduce particle size to a degree of fineness.
Levigation is the process of reducing the particle size of a solid
by triturating in a mortar or on slab with spatula with a small
amount of liquid or melted base
Elutriation Definition: “Elutriation is the process in which the particles of the fluid move in a direction
opposite to that of the sedimentation. (Downward movement)”
Explanation: In gravitational sedimentation the particles will move vertically downward
while the fluid travels vertically upward.
If the velocity of the fluid is less then 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
then 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.
Elutriation is the process of separation of fine particles from course particles. The particles
size can also be measured by this process
