PHYSICOCHEMICAL PROCESSES

d) Miscellaneous processes
Nigarish Ehsan
PharmD , Mphil Pharmaceutics ( PU)
EFFLORESCENCE
Efflorescence
 Definition
 “The spontaneous dehydration of a compound is called
efflorescence.”
 OR
 “The loss of water of crystallization by hydrate and crystalline
substance with water of crystallization) to form anhydrous
salts or hydrate with less molecules of water of crystallization
is called efflorescence.”
 “The property of certain crystalline substances with water of
crystallization, of losing a part of their water of
crystallization and of falling to a powder is said to be
efflorescence, such crystals are known as efflorescent
crystals.”
Principle
 The hydrated substances under normal conditions exert
vapor pressure due to their water of crystallization.
 Vapor pressure in atmosphere due to its water content is
approximately 10 mm Hg. When vapor pressure of hydrated
compound is more than 10 mm Hg then water molecules
escapes from compound into atmosphere and anhydrous
compound is formed
 Example
 Water of crystallization of following substances are removed
by efflorescence,
 CuSO4.5 H2O
 Na2CO3.10H2O
 MgSO4.7H2O
 FeSO4.7H2O

 When Na 2 CO 3 .10H 2 O loses 9 molecules of water it

becomes monohydric Na 2 CO 3 .H 2 O
Precautions
 ➢ The containers that prevent the loss of the water vapours
should be used, to avoid the instability.
 ➢ Store in a cool place because greater the temperature
greater is the release of the water of crystallization.
Exsiccation
Definition
 The process of removing water of crystallization from
crystalline salt or rendering crystalline salts anhydrous is
called exsiccation.
OR
 The process of accelerating the rate of efflorescence by
increasing the temperature (110 -120 °C) is called
exsiccation.
 The difference between efflorescent and exsiccated crystal is
that, the exsiccated substance is necessarily anhydrous.
Examples
 Examples of exsiccated salts used in pharmacy are
 Exsiccated ferous sulphate
 Exsiccated magnesium sulphate
 Exsicated alum
 Substances capable of forming more than one hydrate may be
exsiccated in various stages.
 The temperature use to remove water of crystallization is
very important . For example CUSO 4 .5H 2 O when it is
heated at 30°C then it will lose its two molecules of water
and thus converts into its trihydric form ( CUSO 4 .3H 2 O
)and when it is heated at 100 °C then it will lose two more
molecules of water and gives the monohydric form and when
(CUSO 4. H 2 O) is heated at 200°C then it loses its
molecule of
H 2 O and gives anhydrous (CUSO 4 )
 Similarly Ferrous Sulphate FeSO4.7H2O is heated on water
bath it will lose 6 molecules of water when further heated to
remove last molecule of water decomposition occurs so
ferrous sulphate with one molecule of water will be
considered as exsiccated ferrous sulphate.
 Since exsiccated salts are hygroscopic in nature so it is
necessary to store them in air tight container.
Pharmaceutical applications of
exsiccation
 Exsiccation is done to produce an anhydrous form required
to use in certain medicaments.
 It is also used to reduce bulk and weight of certain drugs so
that they can be easily administered.
 Generally on Exsiccation a fine powder of product is
achieved.
Desiccation
 Definition

 “The process of removing adhered/ admixed moisture from

solids , liquids or gases is called desiccation.”
 The term desiccation refers to the complete removal of water and
the adjective desiccated is applied only to substances from, which
water has been completely removed.

 This is a drying process applied on precipitates, crystals and crude

drugs etc, so in this way they are easily reduced to powder when
desired.
 Solids are dried by placing them in a desiccators which contains
drying agents such as concentrated sulphuric acid or calcium
chloride etc.
 Liquids are dried by placing them over the desiccating agents,
shaking well and then distilling the liquids in the presence of
desiccating agent.
Pharmaceutical applications of
Desiccation
 Aid in Preservation: vegetable and animal drug soon
become moldy and undergo bacterial decomposition if
allowed to remain in moist condition. Desiccation is
absolutely necessary to preserve them.
 Reduce Bulk and Weight: It is also used to reduce bulk
and weight of certain drugs which reduces cost of
transportation and storage.
 To Facilitate comminution: the presence of moisture
gives drug an elasticity and it becomes difficult to powder
them. One of the first step in comminution is to dry the drug
thoroughly to make it brittle and crisp.
DECANTATION
Definition

 “Decantation is the gentle pouring of a liquid with out

disturbing the solid sediments”.
 OR
“The method of separation of a solid from its soluble
impurities”
 Decantation is the process for separation of mixtures,
carefully pouring solution from container in order to leave
precipitates and sediments in the original container.
 Method
 Method consists of allowing the slurry to stand in a
suitable vessel until the solids either settle down at the
bottom.
 Now carefully pouring a solution from a container in order
to leave precipitate (sediment) in the bottom of the original
container.
 Usually a small amount of solution must be left in the
container in order to prevent small amount of precipitates
following with the solution.
APPLICATIONS:
 It is generally used to separate a liquid from an insoluble solid
(e.g. in red wine, where the wine is decanted from the
potassium bi tartrate crystals)
 Separation of liquid from any other immiscible liquid can also
be done decantation . E.g
 the oil and water extracted from olives may be decanted
to obtain the olive oil.
 A mixture of kerosene and water can also be separated
through decantation.
Deliquescence
 DEFINITION

 “Anhydrous substances absorbs moisture from atmosphere.

i.e the reverse of exication.”
 OR
 “The property of certain solids to adsorb moisture from the
atmosphere till the solid converted in to a saturated solution
(i.e. it is converted in to liquid phase) such solid/crystals are
called deliquescents.”
 Examples
 All deliquescent substances are very much soluble in water.
 Examples are
 calcium chloride (CaCl 2 )
 potassium carbonate (k 2 co 3 ) and
 potassium hydroxide (KOH)
Principle:
 The substances have low vapor pressure as compared to
vapor pressure of atmosphere . Under these conditions they
absorb moisture from surrounding atmosphere until a
solution is formed. Such substances are called deliquescent
and the process is called deliquescence .
 Deliquescence is the reverse process of efflorescence. It has
same principle as that of efflorescence (i.e. difference of
vapours pressure)
Hygroscopicity
 DEFINITION

 “The property of certain substances to absorb moisture from

the atmosphere but not converted in to liquid phase (i.e. not
forming saturated solution) is called hygroscopicity and
such substances are called hygroscopic substances.”
 EXAMPLE:
 For example sodium sulphate (Na 2 SO 4 ),
ammonium chloride (NH 4 Cl), aspirin, sodium
hydroxide etc.
ELUTRIATION
 DEFINITION:

 “The process by which there is a separation of particles (i.e.

fine and coarse particles) from the liquids is called
elutriation. In vertical elutriation, the coarse particles settle
down at the bottom due to gravity while fine particles move
upward. While in horizontal elutriation the stream of
suspend particles is passed over a settling chamber.”
 METHOD
 Process of separation of a substance into powder of different
degree of fines by stirring, the substance with a large volume
of liquid in which it is insoluble and withdrawing the liquid at
different heights.
 The upper layer of the liquid contains in suspension the finer
particles, while the lower layers contain the coarser particles.
 It is usually used following a size reduction process with the
object of separating oversize particles which may be returned
for further grinding or discarded.
 The operation is effected on large scale in an elutriating tank
consisting of vessel of large capacity having taps placed at
intervals from top to bottom . So that liquid can be run off at
different levels .
 A similar apparatus can be obtained for its use on small scale
and is known as elutriation jar
APPLICATIONS:
 Chalk is produced from native calcium carbonate by
elutriation . The crude material is first levigated with water.
A large volume of water is then added and the mixture is
stirred briskly after which the upper layer is decanted
carrying with it the finer particles. More water is added to
the liquid remaining in the tank and the operation is repeated
several times.
 Calamine may be produced in the same manner from native
zinc carbonate
 Kaolin is also prepared for pharmaceutical purpose by
elutriation
LEVIGATION
 DEFINITION:
 “The process of particle size reduction by first forming a
paste of solid by adding the minimum amount of suitable non
solvent (levitating agent) and then grinding the paste in the
mortar or on the slab by using the pestle or spatula.”
 The levigating agents are selected on the base of its ability to
form a smooth paste with the substance and on its
compatibility with the product. The levigating agent may be
water light mineral oil and other liquids.
 Only small amount of levigating agent to form the plastic
paste should be used, because excessive amount of levigating
agents will affect the viscosity and the consistency of the
product.
 Small Scale:
 on small scale we use mortar and pestle or slab.
 Large scale:
 On large scale we use series of tanks called Edge Runner
mill.
 Purpose: we used this process to get fine powder or particle
. By using this method we get a smooth paste by grinding the
solid with liquid.
APPLICATIONS IN PHARMACY:
 ▪ It is used to prepare the ointments and pastes

 ▪ It is used to reduce the particle size.

 ▪ This process is also used in making suspensions.

TRITURATION
 Definition:
 ‘Trituration is also the name of the process for reducing the
particle size of a substance by grinding of powders in a
mortar with a pestle “

 Trituration is also the production of a homogeneous mixture

through mixing.
 EXAMPLE:
 dental amalgam is formed by combining particles of an alloy
with mercury .
METHOD
 The correct procedure for preparing such trituration or any
similar dilution of a potent powder medicament to ensure
uniform distribution of the later is :
 Reduce the drug to a moderately fine powder in a mortar.
 Add about an equal amount of diluents and mix well by
trituration in the mortars.
 Successively add portions of diluents and triturating after
each addition until the entire quantity of diluents has been
encorporated.
CENTRIFUGATION
CENTRIFUGATION
 Definition:
 “Centrifugation is a method of separating either two
immiscible liquids or a solid from a liquid”
 OR
 “Centrifugation is a procedure that involves the use of
centrifugal force for the sedimentation of mixture with a
centrifuge used in industry and in laboratory settings. More
dense components of the mixture move away from the axis of
the centrifuge while less dense components of the mixture
move towards the axis
 In comparing relative performance of centrifuges it is useful
to express centrifugal force as a relative force.
 The relative centrifugal force (Ref) is defined as the ratio of
centrifugal force to gravitational force acting upon a given
body
 In centrifugation particles are separated on bases of their
density. It is used to separate biological cells, bacteria and
viruses.
 A particle whether it is a precipitate a macromolecule or a
cell organelle is subjected to a centrifugal force when it is
rotated at a high rate of speed.
 The basic centrifuge consists of two components one is
Electric motor with drive shaft to spin the sample and a
Rotor to hold tubes or other containers of the sample.
 A wide variety of centrifuges are available ranging from a low
speed centrifuge used for routine pelleting of relatively heavy
particles.
 A laboratory tabletop centrifuge. The rotating unit,
called the rotor, has fixed holes drilled at an angle (to the
vertical).
 Test tubes are placed in these slots and the motor is spun.
 As the centrifugal force is in the horizontal plane and the
tubes are fixed at an angle, the particles have to travel only a
little distance before they hit the wall and drop down to the
bottom.
 These angle rotors are very popular in the lab for routine
use.
APPLICATIONS.
 1. High speed centrifuges can be used to separate bacteria
from aqueous fluids.
 2. Centrifugation technique is used to separate glycogen
particles present in the liver cell and separation of viruses
particles from tissue homogenates.
 3. it is used for separation of mixtures where filtration is
difficult i.e. separation of liquids.
 Separation is more rapid with centrifugation .
IGNITION
 Definition:
 ‘’ The process of strongly heating an organic substance in free
excess of air until the carbonaceous matter has been burnt off
as carbon dioxide and the inorganic matter converted into
ash is called ignition.’’
 This process is applied to organic salts of alkali metals such as
tart rates, citrates, benzoates and salicylates etc, which after
ignition leaves an ash of alkali carbonate that can be titrated
with the standard acids giving an indication as to the purity of
the organic salt.
FUSION
m

 Definition:
 ‘’The process of liquefying a substance by heat without the
aid of a solvent is called fusion’’.
 OR
 ‘ Fusion is the process by which the solids upon heating get
converted into liquids without adding solvent. It is also
defined as a process of heating a solid until they melt.
EXAMPLE

Fusion is done to purify certain solids and semisolids

substances.

Beeswax , hard paraffin and wool fat are heated to melt and
filtered while hot to remove impurities.
 METHOD:
 All substances are melt together and then cooled slowly with
continuous stirring until uniform product is obtained
 To avoid overheating substances with higher melting point
are melted first to which substances with lower melting
points are added.
 This method is applied for the preparation of ointments that
contains solid and semisolids in the formulation.
 It is also used for the formation of suppositories.
CALCINATION
 DEFINITION:
 “Calcination is the process in which inorganic substances are
strongly heated so as to remove their volatile contents and a
fixed residue is obtained .”
 On laboratory scale calcination is done on silica or platinum
crucibles whereas in industries metallic vessel is used .
 APPLICATION:
 Calcination is used in preparation of certain inorganic
substances for example calcium oxide,
heavy magnesium oxide, light magnesium oxide, zinc oxide
and red mercuric oxide.

• These substances are prepared by heating their respective

carbonates .

• This method is also used in gravimetric analysis of certain

pharmaceutical preparations .
EVAPORATION
 DEFINITION:
 “The conversion of the liquid in to its vapour without any
external heat is called evaporation.”
 “Theoretically, evaporation means simply vaporization from
the surface of the liquid.”
 “Practically evaporation is the removal of liquid from a
solution by boiling the liquor in a suitable vessel and with
drawing the vapours leaving a concentrated liquid residue.””
 Evaporation differs from boiling that evaporation takes place
at all temperature where as boiling takes place at one
temperature at a given pressure.
 Evaporation occurs only at the surface whereas boiling takes
place from whole of the liquid.
Factors effecting evaporation
 1. Temperature
 The rate of evaporation is directly propotional to
temperature. Increase in temperature increase rate of
evaporation.
 Maximum evaporation occurs at boiling point.
 Heat stable products can be evaporated at high temperature
where as heat labile products will have to be evaporated at
low temperature.
 Extremely heat sensitive substances should be evaporated at
reduced pressure.
 The time required for evaporation is very critical .
 Exposure to a relatively high temperature for a short period
of time may be less destructive of active constituents than a
lower temperature with exposure for a longer time.
 Some drug constituents decomposed more readily in the
presence of moisture especially at a raised temperature due
to hydrolysis.
 2:SURFACE AREA:
 The rate of evaporation is directly proportional to surface
area. The greater the surface area exposed to evaporation
greater will be evaporation.
 3:AGITATION:
 During evaporation the upper layer has a tendency to form
scum or layer. Which lowers the rate of evaporation
4: ATMOSPHERIC PRESSURE:
The rate of evaporation is inversely proportional to
atmospheric pressure on the surface of liquid.
If the atmospheric pressure on liquid is reduced to half then the
rate of evaporation will be doubled.
Due to this reason in many cases evaporation is done under
reduced pressure.
APPLICATION OF EVAPORATION:
 It is the most important process used in preparation of
pharmaceutical products.
 It is used in the preparation of liquid extract, dry extract, soft
extract and in the concentration of blood plasma and serum.
 It is also used in the manufacture of drugs containing
antibiotics, enzymes, hormones and many other substances.
SUBLIMATION
 DEFINITION:
 “ Process of converting a solid directly into vapours without
going through a liquid phase is called sublimation”
 “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.”
 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.
 Desublimation refers to the process in which a gas changes
directly to a solid without going through the liquid state. It is
also known as Deposition.
 Sublimation is an endothermic phase transition that
occurs at temperatures and pressures below a
substance's triple point in its phase diagram.
 EXAMPLE:
 Dry Ice is actually solid, frozen carbon dioxide,
which happens to sublimate, or turn to gas, without
converting into liquid phase.
 Iodine is another example of substance that produces
fumes on gentle heating. It is possible to obtain liquid
iodine at atmospheric pressure and by controlling
temperature above the melting point of iodine.
 Naphthalene also sublimes easily.
 TRIPLE POINT:
 the triple point of a substance is the temperature and
pressure at which the three phases (gas, liquid, and
solid) coexist in equilibrium.
 Principle:
 A solid sublimes only when the pressure of its vapor is below
that of the triple point for that substance. This principle can
be explained by following graph.
Typical Phase Diagram
 Melting Curve – shows the pressure and temperature that a
solid becomes a liquid and visa versa.
 Vapor Curve – shows the pressure and temperature that a
liquid becomes a gas and visa versa.
 Sublimation Curve – shows the pressure and temperature
that a solid becomes a gas and visa versa.
 Triple Point – is the temperature and pressure where all 3
phases of matter can coexist.
 And the graph shows if the vapour pressures of vapour,
formed by the solid, less then 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
 1- The main advantage of sublimation is for purification
process.
 2- The minimum amount of product is loss.

 3- Solvents are not used.

 4- Most traces of any solvent in compound are effectively

eliminated.

 5- Some valuable chemical substances such as

naphthalene, camphor, and benzoic acid etc are purified by
this process.
Vaporization
 DEFINITION:

 “The general term used to denote the conversion of a liquid

into vapour state under any condition of temperature and
pressure is called vaporization”
 When a liquid is kept in a closed evacuated container
molecules from its surface leave continuously and go into the
free space above it known as vaporization.
 Some molecules return to the surface depending on their
conditions in the surface.
 Eventually an equilibrium becomes established when rate of
escape of molecules depend upon the rate of return.
 The vapor is then said to be saturated and the pressure
exerted by vapor is known as vapor pressure.
 The vapor pressure of the liquid depend on the temperature
as the temperature is increased more liquid molecules escape
from surface and vapor pressure is increased.
LYOPHILIZATION
 Definition:
 ‘’ The process of drying in which water is sublimed from the
product after it is frozen is called lyophilisation’’
 OR
 “This is the process in which material to be dried is first
frozen and then subjected under a high vacuum so that a
frozen liquid sublimes leaving only the solid dried component
of the original liquids”
 ’Freeze drying is also known as lyophilisation, gelsiccation or
drying by sublimation,’’
 The temperature and pressure of the substance to be freeze
dried should be less than the triple point.
 Freeze drying depends upon the phenomenon of sublimation
where by water passes directly from solid to vapour state
without passing through the liquid phase.
 Phase diagram for water:
• The above phase graph of water indicates that if the temperature
and pressure is kept below triple point, the ice is directly
converted (sublimed) into vapours.

• This principle is used in freeze drying (lyophilisation) of all the

materials.

 The vapour formed during this process is removed again and again
in order to stop equilibrium produced b/w the vapours and ice.
 this is done by a condenser operating at a very low temperature
i.e. below the freezing point of the solids.
 Stages involved in lyophilisation.
 The process of lyophilisation is completed in the following
stages:
 Pre-freezing.
 Before applying the vacuum, the liquid is firstly frozen, this
process is called pre-freezing and is done by following ways:
 Stages involved in lyophilisation:
 The process of lyophilisation is completed in the following stages:
 1. Prefreezing.
 Before applying the vacuum, the liquid is firstly frozen, this
process is called prefreezing and is done by following ways:

 (a) shell freezing

 In this method 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
 (b) Vertical freezing:
 In this method the bottles are first chilled and then rotated
individually in vertical position in the presence of stream of
very cold air.
 So, by the process small crystals of ice are formed. Moreover
this process is very rapid.
 2. drying:
 After prefreezing, the substance is dried there are two types of
drying,
 1. Primary drying
 2. Secondary drying.

 1. Primary drying:
 It means to supply the latent heat of vaporization. The apparatus
used for this purpose is ‘’vacuum oven’’ or container attached to
individual out let.
 The latent heat of sublimation of substance is provided and so
vapoursformed are removed. By this process 99.5% moisture is
removed .
 2. Secondary drying:
 After primary drying the substance is subjected to vacuum
drying to remove remaining 0.5% moisture. And this is
called secondary drying. During this drying the temperature
must be raised to 50° – 60 °C.
 Packaging:
 The packaging of the freeze dried product is very important
because the freeze dried product 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.
 Advantages of freezedrying:
 Following are the advantages of freeze drying or lyophilisation:
 As it is carried on at very low temp so:
 1.Enzyme action is inhibited.
 2.Decomposition particularly hydrolysis is minimized.
 Porous product is produced during the process which is readily
soluble.
 In freeze dried products salts can not concentrate and so
denaturation of protein does not take place
 Due to low temperature and pressure bacterial growth is less.
 As there is high vacuum, there is no contact with air so oxidation
is minimized.
Mosibat

 PHARMACEUTICAL APPLIACATIONS:
 1. Heat labile (sensitive) products are dried by this process.
 2. Moisture sensitive products are also dried by this process.
 3. Antibiotics are sensitive to water (b/c in water they are
decomposed and lose their (potency) so they are dried by
Lyophilization.
 4. Enzymes are also dried by this process eg. Hyalouranidase.
 5. Hormones like insulin are also dried by this process.
 6. Some micro biological preparations such as culture
(bacterial culture) are prepared by the process of
lyophilisation.
 7. Food products like dry milk also prepared by this process.
 8. Vaccines like, yellow fever, small pox, etc are firstly dried
by this method and then given to the patient.