All slides of seminar emulsions (1)

SEMINAR
TOPIC -Emulsions
EMULSION DEFINATION .
ITS TYPES AND EXAMPLES.
ITS ADVANTAGES AND
DISADVANTAGES.
ITS CLASSIFICATION

EMULSIONS
 Emulsions may be defined as the biphasic system consisting
of two immiscible liquids or phases , one of which is
(dispersed phase) is finely subdivided and uniformly
dispersed as droplets through out the other (the continuous
phase).
 Since such a system is thermodynamically unstable ,a
suitable emulsifying agent is required to stabilize the
system.
 Emulsions are two-phase system in which the dispersed
phase is also a liquid.
 The particle size of the dispersed phase generally ranges
from 0.1 to 100um.

Some Examples….
 A large number of emulsions are available in nature.
Examples are milk , rubber latex , crude oil etc. on the
industrial scale, the commonly encountered emulsions
are food ,(ice cream, cake butter), cosmetics (creams
and lotions), and house hold items (paints , polishes
and insecticides).
 Some emulsions themselves have medicinal properties
,for example liquid paraffin is used as purgative and
laxative.
 Most of the cases, emulsions are used as vehicles for
administration of drugs.

Advantages
1. Mask the unpleasant taste.
2. Economical .
3. Improved dissolution rate and bio availability.
4. Sustained release medication.
5. Nutritional supplement.
6. Diagnostic purposes.
7. Topical use.
8. Flexibility in particle size.
9. Control adsorption rate.

Details …..
1. MASK THE UNPLEASANT TASTE-
Drugs having unpleasant taste are not acceptable
orally. Such drugs can be incorporated in the
dispersed phase(internal phase) so that the taste can
be masked. Examples are laxatives, phenolphthalein
and vitamin A. In other word, emulsions are used as
vehicles for delivering drugs to the body.
2. ECONOMICAL- Expensive solvent (vehicles) are
required to dissolve the lipids(oil soluble drugs).Such
substances can be easily dispersed in less expensive
vehicle such as water. Hence emulsions can be made
available at cheaper cost.

3. IMPROVED BIOAVAILABILITY-
Absorption of drugs has been found to be faster and better when
formulated as emulsions. For example, absorption of griseo-fluvin is
erratic from tablets, whereas if it is given in corn oil-in water
emulsion, its absorption is better. Other examples are insulin and
heparin.
4. SUSTAINED RELEASE MEDICATION
Water soluble antigenic materials are dispersed in mineral oil and are
given as intramuscular injections . These preparation act as depots in
the muscle and release antigen from the oil slowly , over a long
period. Now a day , multiple emulsions (emulsion in emulsion) are also
suggested to provide sustained release of drug.
5.NUTRITIONAL SUPPLEMENT-
Terminally ill-patient are given nutrients parentally. Fats are
dissolved in the oil phase and water soluble nutrients are incorporated
in the aqueous phase. An emulsion prepared in this manner represents
the balanced nutrients in a single dosage form.

6. DIAGNOSTICS PURPOSES-
Radio-opaque emulsions are used as diagnostic material in X-
ray examination
7. TOPICAL USE-
Concentrated emulsion are used in topical delivery as
semisolid vehicles. These have emollient applications.
Examples are cold cream vanishing creams , benzyl benzoate
.etc.
8. FLEXIBILITY IN PARTICLE SIZE-
Although it may be assumed that the smaller the particle
size the better ,it is a uniform product . This is particularly
important if the patient purchases product purchases
product from more than one batch of cream. A company may
choose to use a nano or micro emulsions so various particle
size can be used across a single product.

9. CONTROL ADSORPTION RATE
 Pharmaceutical emulsions can be programmed for rapid or
slow release, depending on what the condition requires. So
if a patient applies the pharmaceutical cream at 0 hour the
active ingredient may be released at both hour 0 or after 1
hour..

DISADVANTAGES
 Emulsions possess certain disadvantages.
1. Emulsion have a short shelf life. They are unstable and the insoluble
phase separates slowely.
2. Being liquid dosage forms , these packed in glass or plastic containers.
Thus care should be taken in handling and storage.
Thus the use of emulsions as pharmaceuticals is declining due to stability
problem.

CLASSIFICATION-
 According to the mode of dispersion:
1. O/W( oil – in – water):
2. W/o ( water in oil)-
3. multiple emulsion.
 In case of consistency.
a). Liquid emulsions
b). Semisolid emulsions.
 In accordance to particle size.
o Coarse emulsions.
o Fine emulsions.
o Micro emulsions.
 According to our route of administration-
o For internal (oral or I.V) OR External use (liniment &lotions).

CLASSIFICATION
 According to the mode of dispersed phase , emulsions are classified as:
1. Oil-in-water type (o/w)
2. Water-in-oil type (w/o)
3. MULTIPLE EMULSIONS..

Water-in-oil type
 An emulsion water in oil, if the dispersed phase(internal phase)is
water and the continous phase (dispersion medium) is oil.
Examples- Moisturising creams , they are also useful as cleansing
creams since they solublize the oil soluble dirt from the surface
 OIL-IN-WATER TYPE-
 In this the dispersed phase is oil and the continuous phase is
aqueous base. This type of emulsion are meant for both internal
and external use.
 External : benzyl benzoate emulsion, benzene hexa-chloride
emulsions.
 Internal : vitamin A in corn oil in water , liquid paraffin in water.

Depending on the globule size emulsions are
classified as follows :
 MICRO EMULSIONS:
Micro emulsions is defined as a system of water oil and amphiphiles
, which is a single optical isotropic and thermo dynamically stable
liquid solution.
Micro emulsions contain globules of the size about 0.01 μ m.
Droplets of such dimensions cannot reflect light, and as a result,
globules are invisible to the naked eyes. Therefore , micro-
emulsions are transparent systems. So they are used for both internal
and external use and have good bio availability than conventional
emulsions.
 FINE EMULSIONS-
Normally these have a milky appearance and the globule size
range from 0.25μm to 25 μm.

MULTIPLE EMULSIONS-
 These are ‘emulsion-within-emulsion; and designated as
w/o/w or o/w/o. For example , w/o/w emulsions is
prepared by incorporating the emulsion w/o in aqueous
phase.
 The drug that is incorporated in the innermost phase must
cross two phase boundaries before getting absorbed.
Multiple emulsion system have been proposed in oral
sustained release or intramuscular therapy. Multiple
emulsions reduce drug loss into an aqueous phase and
improve the encapsulation efficiency
x----------------x------------x

SEMINAR TOPIC- EMULSIONS
SUB TOPICS-
1. APPEARANCE AND
IDENTIFICATION TEST
2. ITS THERMODYNAMICS AND
CAUSES OF INSTABILITY

APPEARANCE AND
IDENTIFICATION
Usually, emulsions may appear as opaque or milky,
however, their appearance may range from a grey
translucence to sparkling clarity. Transparency may
be due to smaller globule size and/or same
refractive indices of external and internal phases.
Milky white emulsion may have a greyish
cast(indicating larger globular size)or bluish
cast(indicating relatively smaller globular size).

CONTINOUS.......
Since the performance of an emulsion depends on its type, it is important
for us to know the type of emulsion with which we are dealing.

DYE SOLUBILITY TEST
This test is based on the principle that the dye can be
dispersed uniformly throughout the phase in which it is
more soluble. For example, amaranth and methylene
blue, water soluble dyes readily tint the water phase of
o/w emulsion, while sudan III and scarlet red, oil
soluble dyes readily colour the oil phase of the w/o
emulsion. Normally, the dye power is dusted on the
emulsion for better results. It is better to sprinkle
water and oil soluble dyes on two samples of the same
emulsion.

For example:-
In case of o/w type, the water soluble dye is miscible indicating the o/w,
whereas oil soluble dye shows immiscibility. Thus, both the tests confirm
the o/w type emulsion.

DILUTION TEST
This test depend on the fact that when a dispersion
medium is added to an emulsion, no phase separation is
possible.
For example:-
When water is added to o/w emulsion, it is freely
miscible with the emulsion and no phase separation
occurs. Similarly addition of oil to w/o emulsion shows
miscibility.

CONDUCTIVITY TEST
This test is based on the stability of water to conduct
electricity. If water is the continuous phase, then the
emulsion conducts electricity.
This can be confirmed by the deflection of indicator in
voltmeter. If oil is the continuous phase, the emulsion
fails to conduct.

CREAMING TEST-
The direction of creaming precisely
identifies the emulsion type, if the
densities of aqueous and oil phases are
known. Water-in-oil emulsions normally
cream downward as oil is usually less
than water. Oil-in-water emulsions
normally cream upwards.

continue…….
Other tests for identification of the type of
emulsion are cobalt chloride test, filter-paper
test and fluorescence test.
These methods are simple, but may give incorrect
results. It is necessary that the results obtained
by one method should always be confirmed by
means of other methods

THERMODYNAMICS CAUSES
FOR INSTBILITY
According to the definition, emulsification is not a
spontaneous process and hence emulsions have
minimal stability. Reasons for instability can be
understood from the nature of immiscible phases
and their interfacial properties.

Emulsions are
thermodynamically
unstable. why?
When polar(aqueous) and non polar(oil) lipids are
mixed together, one of the liquids forms small
droplets and gets dispersed in the other liquid,
forming an emulsion. When left aside, droplets fuse
themselves and finally separate as two layers. This
is an indication of instability of an emulsion. This
state of instability may be described by the fact
that the cohesive forces between the molecules of
the same type are stronger than the adhesive forces
between unlike molecules. Any attempt to increase
the adhesive forces between these phases can
produce a stable emulsion.

continuous….
A system is said to be thermodynamically stable, if it
possesses low surfaces free energy. The higher the
interfacial area, the greater is the interfacial
free energy, and hence lower the stability. When
two immiscible liquid are mixed, one of the
liquids is broken into small globules and gets
dispersed. As a result, globules possess an
enormously surface area compared to its original
surface area.

Consequently, the interfacial
energy increases. The
relationship is:

The system spontaneously tries to change back to
its original state by decreasing ΔA so that will be
zero. The result is the coalescence of globules and
separation of phases. Therefore, emulsions are
described as thermodynamically unstable. From
the physical stability point of view, the process of
coalescence is undesirable. Regrouping of globules
can be prevented to a great extent by adding a
third component called emulsifying agents in
emulsions.

In equation(1), the interfacial tension, γo/w may
be reduced, so that the system can be stable. But
it cannot be made zero, because the dispersed
phases have certain positive interfacial tension.
Hence, the term ΔG in equation(1) cannot be
zero. However, the manufacturing pharmacist
adds surface active agents to reduce γo/w value
to a minimum. Thus, the system can be stabilized
to a certain extent.

Certain emulsifying agents can reduce the
surface tension thereby prevent
coalescence. Such substances are best
suited for the preparation of a stable
emulsion. In spite of the best efforts,
emulsions are still thermodynamically
unstable and exhibit shorter shelf life.

Contents
 Definition
 Bancroft’s rule
 Ideal properties
 Classification
 Natural emulsifying agents from vegetable sources
 Natural emulsifying agents from animal sources
 Semi-synthetic polysaccharides
 Synthetic emulsifying agents
 Inorganic emulsifying agents
 Alocohols

Emulsifying Agents
DEFINITION:-
 Emulsifying agents stabilize emulsions by preventing /reducing
the coalescence of dispersed globules.
 These possess certain degree of affinity to polar and nonpolar
liquids.
 They act as a bridge between the polar and nonpolar phases
and reduce the interfacial tension i.e. oily phase and aqueous
phase and thus makes them miscible with each other and form
a stable emulsion.
 These are also known as EMULGENTS or EMULSIFIERS.

BANCROFT’S RULE
 It describes the relationship between the nature of emulsifying agent ant
type of emulsion formed.
 Emulsion type depends more on the nature of the emulsifying agent than on
the relative proportions of oil or water present or the methodology of
preparing emulsion.
 If the surfactant is more soluble in water, then the aqueous phase becomes
continuous phase, i.e., o/w emulsion will be obtained.
 For example tweens, acacia, bentonite are useful emulsifying agents to
form o/w emulsions.
 Reverse situation is true; the oil soluble emulsifier.
 Spans are employed in the preparation of w/o type of emulsions.

 The phase in which an emulsifier is more soluble
constitutes the continuous phase.
 In o/w emulsions – emulsifying agents are more soluble
in water than in oil(High HLB surfactants).
 In w/o emulsions – emulsifying agents are more soluble
in water than in oil(Low HLB surfactants).

HLB RANGE APPLICATION
4-6 w/o emulsifiers
7-9 wetting agents
8-18 o/w emulsifiers
13-15 detergents
10-18 solubilizers

Determination of HLB
 For polyhydric alcohol fatty acid esters may be calculated with
the formula:-
HLB= 20(1-S/A)
Where, S = saponification number of the ester
A = acid number
 For tall oil and rosin esters, bees wax esters, lanonin esters may
be calculated with the formula:-
HLB= E+P/5
Where, E= weight percentage of oxyethylene content
P= weight percentage of polyhydric alcohol ( glycerol,
sorbitol)

 Emulsifiers with high HLB value (9-16) preferentially
soluble in water  produce o/w emulsions.
 Examples are Tween 80 (HLB 15) and sodium oleate (HLB
18).
 Emulsifiers having low HLB value (3-8) are more oil
soluble and favour the formation of w/o emulsions.
 Examples are span 80 (HLB 4.3) and glyceryl
monostearate (HLB 3.8).
 Combination of emulsifying agent i.e. oil soluble and
the water soluble impart better stability than a single
agent.

 In general, ionic type of emulsifying agents (sodium lauryl sulfate,
triethanolamine stearate) are not recommended for internal use,
because they interact with the biomembranes and adversely affect
the cell functions.
 Emulsifiers stabilize the emulsion, its stability depends upon:-
 Chemical stability of the emulsifier
 Concentration of the emulsifier
 incompatibilities due to use of oppositely charged emulsifiers.

AUXILLARY EMULSIFYINFG AGENTS:-
 These agents themselves cannot form stable emulsions, but act
as thickening agents and help to stabilize the emulsion
examples are:-
 Glyceryl monostearate
 CMC sodium
 Stearyl alcohol
 Stearic acid
 Methyl cellulose
Name of emulsifying agents with HLB value and their
applications:-

Sr.no Name of the
emulsifying
agent
HLB Value Applications
1. Acacia 8 Emulsifying agent
o/w
2. Glyceryl
monostearate
3.8 Emulsifying agent
w/o
3. Sorbitol
monostearate
w/o
4. Polysorbate 20 16.7 Solubilising agent
5. Polysorbate 60 14.9 Detergent
6. Polysorbate 80 15.0 Solubilising agent
7. Sodium lauryl
sulphate
40.0
8. Sodium oleate 18.0 Solubilising agent

Sr.no Name of the
emulsifying
agent
HLB value Applications
9. Tragacanth 13.2 Emulsifying
agent o/w
10. Triethanolamine
oleate
o/w

Ideal Properties Of
Emulsifier
 Compatible with other ingredients of the preparation.
 Capable of reducing the interfacial tension between the two
immiscible liquids.
 Chemically stable.
 Non-toxic.
 Capable to produce and maintain the required consistency of
the emulsion.
 Capable of keeping the globules of dispersion liquid distributed
indefinitely throughout the dispersion medium.

 Not interfere with the stability or efficacy of the therapeutic
agent.
 Promote emulsification and to maintain the stability.
 Little odor, taste and color.

Emulsifying Agents
NATURAL SEMI-SYNTHETIC
POLYSACCHARIDES
Vegetable Animal
Source Source
# Gum acacia # Wool fat # Methyl cellulose
# Tragacanth # Egg yolk # Sodium carboxy
# Agar # Gelatin methyl cellulose
# Pectin
# Starch
# Irish moss (chondrus)

Emulsifying agents
SYNTHETIC INORGANIC ALCOHOLS
# Anionic # Milk of magnesia # Carbowaxes
# Cationic # Magnesium oxide # Cholesterols
# Non- ionic # Magnesium # Lecithins
trisilicate
# Magnesium alu-
minium silicate
# Bentonite

Classification Of
Emulsifying Agents
Natural emulsifying agents from vegetable sources :-
 These are carbohydrates which includes gums and
mucilaginous substances.
 They are anionic in nature and produce o/w type emulsions.
 The emulsions prepared from these emulsifying agents need
suitable preservative to preserve them because the
carbohydrates act as a medium for bacterial growth.

Examples:-
 ACACIA:-
 Considered as best for the extemporaneous preparation of
emulsion foe internal use.
 Emulsions prepared with gum acacia are
- attractive in appearance
- quiet palatable
- stable over a wide range of pH (2 to 10).
 It have low viscosity, therefore creaming take place quite rapidly.

 In order to make a stable emulsion, the other emulsifying agent such as
tragacanth, agar, pectin are also used along with gum acacia which
increases the viscosity of the dispersion medium.
 Gum acacia is used in the following ratio for preparing emulsions from
various types of oils:-
Name of the oil Oil Gum
# Fixed oil 4 : 1
# Volatile oil 2 : 1
# Mineral oil 3 : 1

 TRAGACANTH:-
 Rarely used because it produces very coarse and thick emulsion.
 The appearance and the stability of the emulsion can be improved by
passing the emulsion through a homogeniser.
 A stable emulsion can also be produced if tragacanth is used along with
gum acacia as emulsifying agent.
 AGAR:-
 It is not a good emulsifying agent as it forms a very coarse and viscous
emulsion.
 It is used as emulsifying agents by preparing 2% mucilage, by dissolving in
boiling water and cooled to 45*C.

 PECTIN:-
 It is used as emulsifying agent by preparing 1% mucilage in water.
 It is incompatible with alkalies, strong alcohol, tannic acid and salicylic
acid.
 STARCH:-
 Rarely used because it forms very coarse emulsion.
 It is generally used to prepare enemas.
 IRISH MOSS(chondrus):-
 It is used along with acacia for the emulsification of cod liver oil and to
mask unpleasant odor and taste of the oil.
 Its 3% solution is used to emulsify equal volume of the oil. Used as a
thickening agent.

Natural emulsifying agent with animal sources :-
 WOOL FAT:-
 Used in emulsions which are meant for external use.
 It produces o/w type emulsions and can absorb about 50% of water.
 EGG YOLK:-
 Used in extemporaneous preparations meant for internal use because it get
spoiled during transportation.
 Requires proper preservation and storage in a refrigerator.
 Used as emulsifying agent in the concentration of 12 – 15%.

 GELATIN:-
 Used in the concentration of 1% as emulsifying agent.
 Mainly used for the emulsification of liquid paraffin.
 The emulsion prepared with gelatin is quite white and have an agreeable
taste.
 Needs proper preservation because emulsions are prone to bacterial growth.

Semi-synthetic polysaccharides:-
 METHYL CELLULOSE:-
 It is a synthetic derivative of cellulose.
 Widely used as suspending agent, thickening and emulsifying agent in the
concentration of 2%.
 Commonly used for the emulsification of mineral and vegetable oils, but
get precipitated in the presence of large amount of electrolytes.
 SODIUM CARBOXYMETHYL CELLULOSE:-
 Used as an emulsion stabilizer in the concentration of 0.5 to 1.0%.
 Soluble in both cold and hot water.

Synthetic emulsifying agent:-
 ANIONIC:-
 Various alkali soaps, metallic soaps, sulphated alcohols and sulphonates are
used as anionic emulsifying agents.
 Soap emulsions are used for external applications.
 Sodium lauryl sulphate is commonly used as emulsifying agent among the
sulphated alcohols.
 Produces o/w type emulsions.
 CATIONIC:-
 The quaternary ammonium compounds, such as zalkonium chloride,
benzethonium chloride, cetrimide are used as cationic emulsifying agents.

 Cationic surface active agents bear positive charge on them.
 Used in the preparations meant for external use, such as, skin lotions and
creams.
 NON-IONIC:-
 The glyceryl esters, such as glyceryl monostearate, sorbitan fatty acid
esters such as sorbitan monopalmitate are commonly used non –ionic
surface active agents.
 Widely used in the preparation of pharmaceutical emulsions, because
emulsions prepared with nonionic surfactants remain stable over a wide
range of pH changes.

 Inorganic emulsifying agents:-
 Several inorganic substances such as, milk of magnesium ( 10-20%),
magnesium oxide (5-10%) and magnesium aluminium silicate (1%) are
used to prepare coarse o/w emulsion.
 Bentonite(5%) is used to prepare o/w or w/o emulsions.
 When Bentonite is used to prepare o/w emulsions, oil is added to the
suspension of bentonite.
 When it is used to prepare w/o emulsion, oil is placed in the container and
then bentonite suspension is added to the oil with rapid stirring.

Alcohols:-
 CARBOWAXES:-
 Mainly used in the preparation of ointments and creams.
 Carbowaxes having molecular weight between 200-700 are viscous, light
colored, hygroscopic liquids.
 Carbowaxes with molecular weight 1000 and above are wax like solids.
 A product of desired consistency can be prepared by using right type of
carbowaxes.

 CHOLESTEROL:-
 Cetyl alcohol, stearyl alcohol, cholesterol and glyceryl
monostearate are used to stabilize the emulsion.
 LECITHINS:-
 Lecithins which forms w/o emulsion, is rarely used as an
emulsifying agent because it darkens in color when exposed to
light and gets easily oxidised.

To promote emulsification and maintain stability
 (Emulsifying agent is necessary)
 Question - How do emulsifying agent act in promoting emulsification and maintaining the stability?
 To describe this question many theories have been given
These theories apply specifically to certain types of emulsifying agents
under specific condition
Ph of aqueous phase ratio of internal external phase
nature

Theories
electrical theories
 surface-tension theory
 Oriented-wedge theory
 Plastic or interfacial theory
 Charge repulsion theory
 Steric repulsion theory
 Schulman and Cockbain molecular
complex
formation
 DLVO
 Davies theory

( electrical theories)
 (A) Surface-tension theory
before discussing this theory , one has to aware of the surface tension in liquids
Consider a drop of a liquid which is always in spherical form
Due to internal forces (intermolecular forces)
Promote association of the molecule of substance & resist the distortion
of the drop into a less spherical form
( Fig : formation
of a spherical drop resisting
distortion into less spherical form)

 According to surface-tension of emulsification
 Use of emulsifier or stabilizer lower interfacial liquid between two immiscible liquid
 Reduce repellent force between two liquid & diminish attraction between molecules of same liquid
 Fig: effect of surfactant in reducing the repellent force
 Between two immiscible
 Thus surfactant facilitate the breaking up of large globules into smaller one which have lesser tendency
to
 reunite or coalesce


 When two or more drop of same liquid come into contact with one another
Tendency is for them to join or coalesce, make one larger drop having lesser surface area
than
total surface area of drop
This tendency of liquid measured quantitatively & when surrounding of the liquid is air called
surface tension of liquid
 (Fig. coalescence of
 Water drop)

 When liquid is in contact with a second liquid in which it is insoluble and immiscible, the force
causing each
 liquid to resist breaking up into smaller particles called interfacial tension

 some substance that can
promote the lowering of

r resistance to break-up
&can allow liquid to reduce
 to smaller drops. These
tension-lowering substance
 called surface-
acting(surfactants) or wetting agents

Fig: (a) interfacial tension between two immiscible liquids
(b) coalescence of drop of same liquid if interfacial tension is not reduced

(B) Oriented-wedge theory
 According to this theory , emulsifying agent (surfactant) curved around a droplet of the internal
phase
 Of the emulsion .
 (BASED ON FACT )- Certain emulsifying agents orient themselves about & within a liquid depending
on
 their solubility in that particular liquid. If a system contain two immiscible
liquid
 and an emulsifying agent is added to that system, the embedded more
deeply in
 one of the phases in which it is more soluble than the other phase.
 EXAMPLES :
 soap have a hydrophilic or (water-loving portion) and a hydrophobic (water-
hating
 portion) , orient into each phase according to their respective intimacy


Emulsifying agent having greater hydrophilic character Emulsifying agent having greater hydrophobic
than hydrophobic character character than hydrophilic character
Promote an oil-in-water emulsion promote an water-in-oil emulsion
Fig: emulsifying agent(more hydrophilic) Fig: emulsifying agent(more hydrophobic)
surround o/w drop surround w /o drop

(C) Plastic or interfacial film theory
Theory describes
that the emulsifying
agent is located at
the interface
between the oil and
water
Forming a thin film
by being adsorbed
onto the surface of
the internal phase
droplets
The film prevents
the contact and
subsequent
coalescence of the
dispersed phase
A tougher and more
pliable film will
result in greater
physical stability of
the emulsion.

Formation of film on oil droplet
(a) the most stable emulsion
since two emulsifying agents
are adsorbed on the surface of
globules in their best possible
fashion, forming strong and
pliable film
(b) is fairly stable emulsion
since a film of single
emulsifying agent adsorbed on
the oil globule and form a
rather less strong film
(c) is poorly stable emulsion
since a weak film of one
emulsifying agent is formed
which does not protect the
contact between the
dispersed globules

(d) charge repulsion theory
This theory of emulsion says that the fine globules of dispersed phase are separated
due to the repulsive forces
developed as a result of the nature of emulsifying agent(anionic or cationic) or by
adsorbing ions form the dispersion medium
The charge develop on the surface of oil globules is great enough to cause repulsion
between the droplets
which act as an electrical barrier to prevent coalescence of the oil droplet & allow the
oil phase to remain in droplet form,
uniformly dispersed in continuous water phase

 Fig : development of repulsion due to adsorption of cationic
emulsifying agent on oil globules

(e) Steric repulsion theory
 This theory says that the repulsion develops between the water droplet due to the long
hydrocarbon chain of emulsifying agent which has been adsorbed on their surface
this repulsion called steric repulsion
preventing contact or coalescence of water
droplet
 Fig : development of steric repulsion due to long hydrocarbon chain of emulsifying agent
 between water droplet

(Electrical theory)
(a) Schulman and cockbain molecular complex formation
They used
emulsifier mixtures
(combination of
ionic surfactants
and fatty alcohols)
Are similar to ionic
emulsifying waxes
that are currently
used in
formulations to
stabilize emulsion
According to
Schulman and
Cockbain theory, it
was revealed that
molecular
interactions arising
at a (oil-droplet)/
water interface
were correlated
with the molecular
interactions at an
air/water
interface.
In this context, the stability of interfacial film
of oil-in-water emulsions was running
correspondingly to the stability of the
monolayer interfacial film at the air/water
interface which normally composed of a stable
complex of two components, i.e. oil soluble
substance and water soluble substance.
The stability of this condensed interfacial
film at air/water interface depends upon
the interactions between polar head
groups of the components and van der
Waals forces of attraction between the
respective non-polar parts.

 As reasonable to w/o interface ( an amphiphilic molecule) align itself at a w/o
interface in the most e energetically favorable position i.e. oleophilic portion in
oil phase & hydrophilic portion in aqueous portion
 It is also established that the surfactant tend to concentrate at interface and that
emulsifier adsorbed at o/w interface as monomolecular film
 If the concentration of emulsifier is high enough
It form rigid film between the immiscible phases, which act as mechanical bar to
both adhesion and
coalescence Of the emulsion droplet
 Thus the surfactant at the interface of emulsion droplet show the stable emulsion

Above concept
illustrated by study of
Schulman and cockbain
 Fig : schematic representation of relationship mixed film formation,
mechanical strength & stability of emulsion from( Schulman & cockbain)
 (a) cetyl sulfate Na , cholesterol(closely packed condensed complex excellent
emulsion
 (b) cetyl sulfate Na, oleyl alcohol no closely packed condensed complex poor
emulsion
 ( c) cetyl oleate fairly closely packed monolayer, negligible complex formation
rather poor emulsion
(1)
 o/w emulsion stabilized by mixtures of sodium cetyl sulfate and
cholesterol, which were known from other experiment to form rigid and tightly
packed films.
 (2)
 when oleyl alcohol was substituted for cholesterol the steric effect of a
double bond resulted in the formation of a poor interfacial complex and
emulsion stability was proportionately low.
 (3)
 in last the sodium oleate and cetyl alcohol possible obtain a rather poor
emulsion but one that was more stable than of previous case .
 Thus a tightly packed emulsifier film contribute to the stability of emulsion

 The steric argument by Schulman and cockbain has been used to explain the well-known
fact that mixed emulsifiers are often more effective than single emulsifier.
 the ability of the mixture of emulsifiers to pack more tightly contribute to the strength of
the film, & hence to the stability of the emulsion .
 Most emulsifier probably form fairly dense gel structure at the interface and produce a
stable interfacial film.
Electrical double layer :
It has just been described how interfacial films alter the
rates of coalescence of droplets by acting as barrier. In addition the same or similar film can
produce repulsive electrical force between approaching droplet. Such repulsion is due to the
electrical double layer.
The concept of electrical double layer at the interface can be illustrated with the help of fig
That the solid particles are dispersed in an aqueous solution containing an electrolyte

fig : concept of electrical double layer at the
solid-liquid interface
distribution of ions is shown. aa’
positive charge; bb’positive charge
cc’ electrically neutral .The system
as a whole is electrically neutral
 The interface : aa’ is the solid/liquid interface. The cations are assumed to be present in solution.
 these are adsorbed on the solid interface and impart a +ve charge. These
cation
 are referred as potential determining ions.
 Electrical double layer consist of
 Tightly bound layer diffuse second layer

 bulk liquid phase

 Tightly bound layer : aa’ is a region of tightly bound layer. This layer extend upto bb’ .

 Once adsorption is complete, the cations attract a few anions & repel the approaching
cations.

Further thermal motion tends to produce equal distribution of ions in solution.
 Thus at equilibrium some excess anions are present in this region.

 However their number is less than the adsorbed cation therefore bb’still possesses positive
charge.
 Anions are normally termed as counter ions or gegenions.

 When particles move relative to the liquid, this tightly bound layer also moves along.
 Thus the particle surface now extend up to bb’ rather than aa’ the boundary bb’ is termed as
shear plane

 Diffuse second layer :
 This region is bound by lines bb’ & cc’. In this layer, excess
negative ions are present

 At & beyond cc’ the distribution of ions is uniform. On the whole the system is
electrically neutral, even though the distribution of ions is unequal in different
regions.
 In the fig bb’ may possess –ve charge. It indicates that the number of anions is
more compared to that of cations adsorbed on the interface
However cc’ still maintain electrical neutrality . When the interface is adsorbed by –
ve ions then aa’ assume –ve charge & cc’ will be neutral. Depending on distribution
aa’ can be -ve , bb’= +ve, cc’= neutral.

When we move from the interface aa’ towards the bulk of dispersion dd’ the potential changes
These changes are characterized and expressed by different ways
Nernst potential zeta potential
Nernst potential : It is the potential of the solid surface itself, aa’ owing to the presence of
potential
determining ions.
Nernst potential, E or electro thermodynamics potential is defined as the difference in
potential between the
Zeta potential : it is the potential observed at the shear plane i.e. bb’ line.
Zeta potential or electrokinetic potential is defined as the difference in the potential between
the surface of
the tightly bound layer (shear plane) and the
electroneutral region of
the solution in a dispersion.

Zeta potential : defined as the work required to bring a unit charge from infinity to
the
 surface of the particles.
 from fig it can be inferred that the potential energy decreases rapidly in
the initial
 stage, followed by a gradual decreases towards the boundary cc’. The
 counterion, which are present close to the surface bb’ & in the region of
bb’ to cc’
 may reduce the particle-particle interaction. Hence the potential energy
decreases
 more gradually in this region.

 zeta potential is more as compared to Nernst potential because electrical
double
 layer also moves, when the particle is under motion.
 Fig : zeta potential at liquid-solid
 boundary. Curve shown for the
 fig discuss above of electrical double layer

application:
 zeta potential govern the degree of repulsions between the adjacent ions of like
charges. Hence it is used to predict particle-particle interaction. Such information
provide information about the stability of system containing dispersed particle.
 an optimum zeta potential is desirable for the maximum
stability.
 if zeta potential fall below a particular value, the attractive forces exceed the repulsive
forces. This result in the aggregation of particles. This phenomenon is observed in colloids.
zeta potential decreases more rapidly when the concentration of electrolyte is increased or
the valency of counter ions the higher


DLVO theory (derjaguin, landau, verway and overbeek theory)
 (Stability of the dispersion is explained on the basis of DLVO theory)
 According to this theory, the distance between two dispersed particles mainly influences
particle-particle interaction.
 Using this theory , one can approximately determine the amount of electrolyte( of a
particular valency type) required to precipitate or stabilize a colloid.
 In a colloidal dispersion, the Brownian motion results in frequent collision between particles.
Such interaction are mainly responsible for the stability of colloids.
 They are two types of interaction , namely attraction and repulsion.
When attractions predominate, the particle adhere after collision and aggregate. When repulsion
predominate the particle rebound after collision and remain individually dispersed.
 The potential energy versus interparticle distance for particle in dispersion in a given figure

Fig :potential energy versus interparticle
distance for particle in suspension

The interaction between particles are described as follow :
 (a) vander waals attraction (b) electrostatic repulsive forces
(c) net energy of interaction
(a) Vander waals attraction : These forces depends mainly on the chemicals nature and sizes of the
particle
these forces are London-type and cannot be readily. The
potential energy of
attraction is represented by VΑ.
(b) Electrostatic repulsive forces : the electrostatic repulsive forces depend mainly on the density
, surface
charge and thickness of the double layer. These
indicate the magnitude zeta
potential. The potential energy representing
repulsion is donated by VR
(c ) net energy of interaction : an algebraic addition of the above two curves give the net energy of
interaction. The potential energy is represented by VT.


Conclusion from energy curves
 (a) primary minimum ( sign of precipitate) : when particle are very close to each other, atomic
 orbital overlap and penetrate into each other. This is
indicated by a
 rapid rise in potential energy. The net result is a
stronger attraction
 which leads to precipitate.
 (b) net energy peak (sign of better stability) : at intermediate distance appreciable repulsive
 forces operate(+ve zeta potential energy). The potential barrier
keeps the
 particle in Brownian movement and imparts stability to the
 dispersion. At this peak, the maximum potential is designated
by
 VM.

the stability of a colloids system is defined by the height of the maximum in the potential
energy curves
The value of VM is about 10 to 20 KT ,( where K is Boltzmann constant and T is the absolute
temperature )Which corresponds to a zeta potential of about 50 mV. Such a system is
considered kinematically stable. The potential energy barrier must be surmounted, if the
colloidal particles approach each other sufficiently close to fall into the deep primary minimum
of reversible coagulation.
 ( c) secondary minimum(sign of aggregation) : this is observed when the particle are
 separated by lon distances, about 1000 to 2000A
 particle experience attraction forces and form
 aggregate. The presence of a secondary minimum
 is taken advantageously in the controlled flocculation
 of coarse dispersion. Small colloidal particle do not
 form aggregate, because the minimum energy(Vm)
 is the same order of thermal energy of the particle.
 thus aggregation is reversed by Brownian

summary
 According to DLVO theory colloidal particle coagulate whenever their
kinetic energy is sufficient to surmount the potential energy barrier VM
 Thus the coagulation of colloidal particles may be accelerated by two
ways
 (a) by reducing the height of the potential barrier
 (b) by increasing the kinetic energy of particles

Davies theory
 In 1957, Davies suggested a method based on calculating a value based on the chemical groups of
the molecule(calculated the HLB values for surface active agents by splitting the various surfactant
molecules into their component groups, to each of which is assigned a group number)
(HLB) hydrophilic-lipophilic balance
 HLB is an arbitrary scale (number system) the indicate the extent of polar-non polar nature of the
amphiphiles( surfactants).
 One empirical selection system is HLB as proposed by griffin and described by Davies notably in
1957.
 Surfactant such as spans( sorbitan ester) are lipophilic have low HLB value (1.8 to 8.6)
 On the other hand, tween (polyoxyethylene derivatives of spans ) are hydrophilic have high HLB
value (9.6 to 16.7)
 The HLB scale is used to identify the optimum efficiency of a variety of surfactant
 A HLB value of one 1 indicate that surfactant is soluble in oil & 20 implies that it is soluble in water

Method of estimation
 method 1 : the chemical structure of a molecule is split into different component group. Each group is
 assigned a number. The algebraic sum of these number for their respective group
permit
 calculation of its HLB values.
HLB = Σ(hydrophilic group number )- Σ(lipophilic group number) +7
for examples : the structure of sodium lauryl sulfate
method 2 : in this method, each atom or group has been assigned a constant. They are used for the
calculation thus, experimental estimates can be avoided.
For example : when a surfactant contain polyoxyethylene chain HLB value can be
estimated
by equation.
HLB = E + P
 5

 WHERE
 E = percent by weight of ethylene oxide chain
 P = percent by weight of polyhydric alcohol group (example glycerol, sorbitol)
 The HLB value of beewax and lanolin derivatives can be estimates by this method
 Method 3 : if surfactant contain ester functional groups such as glyceryl monostearate, the HLB
value can be
 estimated using equation
 HLB = 20 1 - S
 A
 where
 S = saponification number of the ester
 A = acid number of the fatty acid
 For example : HLB value of polyoxyethylene sorbitan monostearate(tween 80 )

Required HLB(critical HLB)
 It is the hydrophilic- lipophilic value that is desired in order to prepare a
stable emulsion of o/w or w/o type.
 The required HLB value is calculated based on the oil phase and the type of
emulsion. A few example below
Oil phase o/w w/o
Cotton seed oil 6-7 ---
Mineral oil 10-12 5-6
beeswax 9-11 5
Paraffin wax 10 4

 It is assumed that HLB of a mixture of two surfactant containing the fraction ƒ, of A and (1 –ƒ )
of B is an algebraic mean of the two HLB values
 HLBmixture = ƒ . HLB + (1 – ƒ ) HLBB
Advantages :
 the HLB value can be used to check the properties of surfactant of molecule.
<10 : lipid-soluble(water-insoluble)
>10 : water-soluble (lipid-insoluble)
1.5 to 3 : anti-foaming agent
3 to 6 : w/o emulsier
7 to 9 : wetting agents
13 to 15 : detergent
12 to 16 : o/w emulsier
15 to 18 : solubiliser
 It is use to correlate the characteristics of surfactant with the properties that are needed to
make various heterogeneous system

 Disadvantages :
 HLB provide information regarding the nature of the surfactant used but the
concentration of such surfactant is equally important. The HLB system
neglect the concentration of surfactant required for the optimum stability of
emulsion
 Though HLB of a surfactant indicates the solubility properties , it is an over-
simplification. It cannot be always realistic. Because in general, solubility
depends on the nature of solvent, temperature and presence or absence of
additives.

Hydrophilic Groups Group Number
-SO4
−Na+ 38.7
-COO−K+ 21.1
-COO−Na+ 9.4
N (tertiary amine) 9.4
Ester (sorbitan ring) 6.8
Ester (free) 2.4
-COOH 2.1
Hydroxyl (free) 1.9
-O- 1.3
Hydroxyl (sorbitan ring) 0.5

Lipophilic Groups Group Number
-CH- -0.475
-CH2- -0.475
CH3- -0.475
=CH- -0.475

Emulsifying agents help to stabilize the emulsion. inspite of
best efforts ,emulsions tend to be unstable. signs of
instability are enumerated below
1.FLOCCULATION
2.CREAMING
3.COALESCENCE
4.BREAKING
5.PHASE INVERSION

FLOCCULATION
 Flocculation is defined as the association of globules
with in an emulsion to form large aggregates ,which can
be easily redispersed upon shaking.
 In an emulsion, neighboring globules come closer to
each other and form colonies in the external phase.
 Aggregation of globules is not clearly visible. This is
probably the initial stage that leads to instability. The
extent of flocculation of globules depends on

 (a) Globule size distribution
 (b) charge on the globule surface
 (c) viscosity of the external medium
 Uniform sized globules prevent flocculation. This can be achieved by
proper size reduction process. A charge on the globules exert repulsive
forces with the neighbouring globules.

 If the viscosity of the external medium is increased ,the
globules become relatively immobile and flocculation
can be prevented. This can be achieved by adding
viscosity improving agents(bodying agent or
thickening)such as HYDROCOLLOIDS OR WAXES. Flocs
slowly move either upward or downward leading to
creaming. Flocculation should not be confused with
creaming. Flocculation is due to interaction of
attractive and repulsive forces, whereas creaming is
due to density differences in the two phases.

CREAMING
 Creaming is the concentration of globules at the top or
bottom of the emulsion. The flocules move either
upward or downward leading to creaming. Creaming
may also be observed on account of the movement of
individual globules.
 It can be observed by difference in colour shade of the
layers.

 It is a reversible process, i.e., cream can be redispersed
easily by agitation .This is possible because the oil
globules are still surrounded by the protective sheath of
the emulsifier.
 This is a potential step towards complete coalescence
of internal phase. Hence, this stage is also considered
to be the mark of instability. In creaming, the drug is
not uniformly distributed. This leads to variable dosage.
Therefore, the emulsion should be shaken thoroughly
before use.

 Creaming is of two types
 (A) UPWARD CREAMING
 (B) DOWNWARD CREAMING
UPWARD CREAMING:-
This is due to the less denser internal phase. This is
normally observed in oil in water emulsions.

DOWNWARD CREAMING:-
Downward creaming is possible if the internal phase is
heavier.
Due to gravitational pull, the globules settle down. This
is normally the case in water in oil emulsion .since
creaming process involves the movement of globules in
the emulsion, Stokes law can be applied.

CREAMING CAN BE
INFLUENCED BY
 (1)GLOBULE SIZE
 (2)VISCOSITY OF THE DISPERSION MEDIUM
 (3)DIFFERENCE IN THE DENSITIES OF DISPERSED PHASE
AND DISPERSION MEDIUM

CREAMING CAN BE
PREVENTED BY
 (1)Reducing the particle size by homogenisation.
Doubling the diameter of oil globules increases the
creaming rate by a factor of four.
(2)Increasing the viscosity of the external phase by adding
the thickening agents such as tragacanth or sodium
alginate.

 (3)Reducing the difference in the densities between the
dispersed phase and dispersion medium. In general, the
density of aqueous phase is higher than the oil phase.To
make densities equal,oil soluble substances such as
beta-bromonepthalene, bromoformare addedto the oil
phase. This technique is rarely used in practice.

coalescence
 A few globules tend to fuse with each other and form
bigger globules. In this process,the emulsifier film
around the globules is destroyed to a certain extent.
This step can be reognised by increased globule size and
reduced number of globules.

COALESCENCE IS OBSERVER
DUE TO
 (1)Insufficient amount of the emulsifying agent
 (2)Altered partitioning of the emulsifying agent
 (3)incompatibilities among emulsifying agents.
 Phase volume ratio represents the relative volume of
water to oil in an emulsion.
 At higher ratio(<74% of oil to water),globules are closely
packed, wherein small globules occupy the void spaces
between bigger globules. Thus, globules get compressed
and become irregular in shape. which leads to fusion of
adjacent globules.

BREAKING
 This is indicated by complete separation of oil and
aqueous phase. It is an irreversible process,i.e., simple
mixing fails to resuspend the globules into an uniform
emulsion. In breaking, the protective sheath around the
globules is completely destroyed.

PHASE INVERSION
 The involves the change of emulsion type from oil in
water to water in oil or vice versa. when we intend to
prepare one type of emulsion say oil in water, and if the
final emulsion turns out to be water in oil,it can be
termed as a sign of instability.

TOPIC-FACTORS IMPROVING
PHYSICAL STABILITY
Presented to-Mrs. Manpreet kaur Walia
Presented By-Shivangi Abrol
Roll No.-1502001094
Batch-B2

 STABILITY OF EMULSION
 An emulsion is said to be stable if it is remains as such
after its preparation i.e. the dispersed globules are
uniformly distributed throughout the dispersion medium
during medium during its storage.
 The emulsion should be chemically stable and there
should not be any bacterial growth during its shelf life.

 The following three changes usually occurs during the
storage of an emulsion:
 CRACKING
 CREAMING
 PHASE INVERSION

CRACKING:
 cracking means the separation of two layers of disperse and
continuous phase, due to the coalescence of disperse phase globules
which are difficult to redisperse by shaking .
 cracking may occurs due to the following reason:
BY ADDITION OF EMULSIFYING AGENT OF OPPOSITE TYPE:
 Soaps of monovalent metals produce o/w type emulsions whereas
soaps of divalent metals produce w/o type emulsion
 But the addition of monovalent soap to a divalent soap emulsion or a
divalent soap to a monovalent soap emulsion leads to cracking of
emulsions.
BY DECOMPOSITION OR PRECIPITATION OF EMULSIFYING AGENT:
 When an acid is added to an alkali soap emulsion (turpentine
liniment),it cause the decomposition of an emulsifying agent and
thus leads to cracking of an emulsion.

 Similarly, when sodium chloride is added to sodium or potassium soap
emulsion, it leads to the precipitation of emulsifying agents and thus
cracking if emulsion take place.
BY ADDITION OF A COMMON SOLVENT:
 When a solvent is added to an emulsion which is either miscible with or
dissolve the dispersed phase, the emulsifying agent and and continuous
phase, there is formation of one phase or a clear solution.
 this leads to cracking of an emulsion
 For example, addition of alcohol to turpentine liniment leads to the
formation of clear solution because turpentine oil, soft soap and water
are soluble in alcohol.
BY MICROORGANISMS:
 If emulsion are not stored properly, they may develop bacterial and
mould growth.
 This may lead to destruction of emulsifying agent and cause cracking of
emulsion.
 Therefore, it is desirable that all emulsions which are required to be
stored for a long period should be suitably preserved

 CHANGES IN TEMPERATURE
 when emulsion are stored for a long time, and increase
in temperature may reduce the viscosity of the emulsion
and encourage creaming.
 when emulsion are stored at very low temperature,
freezing of its water content into ice and subsequent
melting of the ice and shaking may reform the emulsion

 BY CREAMING
 A creamy emulsion is more liable to crack than a homogeneous emulsion.
 Therefore it is necessary to take steps to retard creaming as far as possible.
 CREAMING
 Creaming may be defined as the upward movement of dispersed globules to form a thick layer at the surface of the
emulsion.
 Creaming is a temporary phase because it can be re- distributed by mild shaking or stirring to get again a homogenous
emulsion.
 As far as creaming of the emulsion should be avoided because it may lead to cracking with complete separation of
two phases.
 According to stoker's law, the rate² of creaming depend on the number of factors which can be explained by the
following equation:-
V = 2r²(d1-d2)g
9ŋ
where V = rate of creaming
r = radius of globules
d1 = density of continuous phase
d2 = density of continuous phase
g = gravitational constant
ŋ = viscosity of the dispersion medium

 RADIUS OF GLOBULES
 The rate of creaming is directly proportional to the radius of
the globules.
 Larger the size of globules, the more will be creaming and
smaller the size of the globules, lesser will be creaming.
 The small globules will rise less quickly than large globules
by passing the emulsion through a homogenizer.
 DIFFERENCE IN DENSITY OF DISPERSE PHASE AND
CONTINUOUS PHASE
 The rate of creaming depends upon the difference between
the densities of the disperse phase and continuous phase.
 Greater the difference, more will be the creaming.
 This difference can be reduce but it is not desirable because
it is not required therapeutically.

 VISCOSITY OF THE DISPERSION MEDIUM
 The rate of creaming is inversely proportional to the
viscosity of the dispersion medium.
 The viscosity can be increased by adding tragacanth and
methyl cellulose but too much viscosity is undesirable
because it may become difficult to re-disperse the material
which have settled at the bottom.
 Moreover, it is difficult to pour the emulsion from the
container
 STORAGE CONDITION
 The emulsion should be stored in a cool place because the
rise in temperature reduces the viscosity which may lead to
creaming.
 The freezing should be avoided because it may lead to
cracking

 PHASE INVERSION
 Phase inversion means the change of one type of
emulsion into the other type i.e., oil in water emulsion
change into water in oil and vice versa.
 It may be due to following reasons:-
 By the addition of an electrolyte
 By changing the phase -volume ratio
 By temperature change
 By changing the emulsifying agent.
 The phase inversion can be minimized by keeping the
concentration of disperse phase between 30 to 60%,
storing the emulsion in a cool place and by using a
proper emulsifying agent in adequate concentration.

FACTORS IMPROVING PHYSICAL
STABILITY
 1 Theories related to the stability of emulsions are same as those
mentioned in suspensions i.e Brownian movement and sedimentation
.
 2 Factors which are empirically obtained from these theories and their
influence on stability are discussed here.
 3 Factors that influence stability are monitored closely during
production.

 Particle Size:
1 As the globule size is reduced (to fine state of subdivision) they tend to
exhibit Brownian movement (Example is microemulsion size 0.01.
2 According to Stoke’s law, the diameter of the globule is considered as
the major factor in creaming of emulsions.
3 In general , the rate of creaming decreases four fold, when the globule
diameter is halved.
4 In microemulsions, the rate of creaming is insignificant.
5 On the industrial scale, emulsion are passed through a colloid mill.
6 After preparation and during aging, emulsions are also evaluated for
particle size.

 Particle Size Distribution:
1 In general, globules of uniform size impart maximum stability.
2 In such emulsion , globules pack loosely and globules to globules contact
is less.
3 However, it is difficult to achieve a monodisperse system due to variety
of factors such as viscosity, phase volume ratio,density of phases.
4 Hence , an optimum degree of size dispersion range should be chosen to
achieve maximum physical stability.
5 Size distribution analysis has been a common procedure in the
evaluation of physical stability of emulsions.

 3 Viscosity
1 As the viscosity increases, flocculation of globules will be reduced
because the mobility of globules is restricted.
2 The Brownian movement of globules will also be hindered, leading to
creaming.
3 Viscosity factor is normally considered for the industrial production of
emulsions.
4 Various thickening agents such as tragacanth ,veegum and cellulose
derivatives are employed to formulate emulsions for internal use.
5 Viscosity determination is also an important quality control tool in
product evaluation.

 4 Phase Volume Ratio:
1 In an emulsion the relative volume of water and oil is expressed as
phase volume ratio.
2 In general , most medicinal emulsions are prepared with a volume ratio
of 50:50.
3 This proportion brings about loose packing of globules.
4 Uniform spherical globules in loose packing have a porosity of 48% of the
bulk volume.
5 The remaining volume 52% is occupied by the globules.

 5 Charge Of Electrical Double Layer:
1 When an ionic type of emulsifier is employed , the electrical double
layer (interface between oil and water) possesses charge.
2 The repulsive forces due to like charges on the surface of globules,
prevent the flocculation of globules.
3 The charge on the electrical double layer also depends on the PH of the
preparation .
4 When non ionic emulsifiers are used , this factors has no importance.

 6 Physical Properties of Interface:
1 The interfacial film of the emulsifier is responsible for enhancing the
stability of the product.
2 The film should be elastic enough to form rapidly as soon as droplets are
produced.
3 This behavior facilitates the production of emulsions.
4 On moderate shaking ,the emulsion should be reconstituted.
5 The film should be tough so the coalescence of globules can be
prevented.
6 The physical properties of interface depends upon the pH of the
preparation.

 7 Densities of Phases:
1 It is not usual practice to adjust the density of the phase to the same
value.
2 Oil phase density can be enhanced by adding brominated oil, when the
oil is an external phase.

 8 Temperature Fluctuations :
1 Elevated temperatures alter the partition characteristics of the
emulsifier and preservatives.
2 Temperature also enhance the chemical degradation of drugs and other
ingredients.
3 At higher temperatures, the external phase water may evaporate
making the product more concentrated.
4 At lower temperature , the aqueous phase may contain ice crystals,
which rupture the interfacial film and break the emulsion .

 9 Poor Experimental Techniques:
1 These often lead to incomplete emulsification .
2 Hence, the process conditions including the sequence of steps should be
meticulously followed during manufacture.

FACTOR S IMPROVING
PHYSICAL STABILITY
OF EMULSIONS

Factors
 Particle Size
 Particle Size Distribution
 Viscosity
 Phase Volume Ratio
 Charge Of Electrical Double Layer
 Physical Property Of Interphase
 Density of Phases
 Temperature Fluctuation
 Poor Experimental Tecniques

PARTICLE SIZE
As the globule size is reduced, they tend to exhibit brownian movement,
(example is microemulsion , size 0.01 um) . According to stoke’s law, the
diameter of the globule is considered as a major factor in creaming of
emulsions. In general, the rate of creaming decreased four fold, when the
globule diameter halved. In microemulsions, the rate of creaming is
insignificant. It is necessary to choose the optimum globule size for
maximum stability. On the industrial scale, emulsion are passed through a
colloid mill in order to achieve size reduction of globules.

Particle Size Distribution
 In general, globules of uniform size impart maximum
stability. In such emulsions, globules pack loosely and
globule to globule contact less. However , it is difficult
to achieve a monodisperse system due to a variety of
factors such as viscosity, phase volume ratio . Hence an
optimum degree of size dispersion range should be
chosen to achieve maximum physical stability. If the
size of globule is not uniform, than globule of smaller
size occcupy the space between the larger globules.

Viscosity
 As the viscosity increases, flocculation of globules will
be reduces because the mobility of globules is
restricted. Simultaneously the broanian movement of
globules will also be hindered, leading to creaming. So,
an optimum viscosity is desireable for good stability .
Viscosity factor is normally considered for the industrial
production of emulsion.

Phase Volume Ratio
 In an emulsion the relative volume of water and oil is
expressed as phase volume ratio. In general, most
medicinal emulsion are prepared with a volume ratio of
50:50, This proportion brings about loose packing of
globules. Uniform spherical globules in loose packing
have a porosity of 48% of the bulk volume. The
remaining volume is occupied by the globules.

Charge OF Elecrical Double
Layer
 When ionic type of emulsifier is employed, the
electrical double layer posses charges. The repulsive
forces, due to like charges on the surface of the
globules, prevent the flocculation of globules. The
charge on the electrical double layer also depend the
pH of the preparation. In general , the influence of
charge of electrical double layer is of secondary
importance. When non-ionic emulsifier are used, this
factor has no importance.

Physical Properties Of
Interface
 The interfacial film of the emulsifier is responsible for
enhancing for the satability of the product. The film
should be elastic enough to form rapidly as soon as
droplets are produced. This behaviour facilitates the
production of emulsions. Similarly on moderate shaking,
the emulsion should be reconstituted. After
manufacture, the film should be tough so that
coalescence of globule can be prevented. Suitable
emulsifying agents should be selected to achieve the
above film properties at the intrface. The physical
properties of interface depends on the pH of the
preparation. Therefore, optimum pH has to be
maintained for maximum stability.

Densities Of Phases
 It is not an usual practice to adjust the density of the
phases to the same value. Oil phase density can be
enhanced by adding oil, when the oil is an external
phase.

Temperature Fluctuations
 Elevated temperature alter the partition characterstics
of the emulsifier and preservatives. The net result is
instability . Temperature also enhances the chemical
degradation of drugs and other ingredients. The
chemical instability also leads to physical instability. At
high temperature , the external phase water may
evaporate making the product (o/w) more
concentrated.
 At lower temperature , the aqueous phase may contain
ice crystal, which rupture the interfacial film and break
the emulsion . Care should be taken to prevent
temperature fluctuation during manufacture and
storage.

Poor Experimental
Techniques
 These often lead to incomplete emulsification . Hence ,
the process conditions including the sequence of steps
should be meticulously followed during manufacture.
Besides, factors mentioned above , it is also to prevent
the growth of microorganism.

Introduction…
 Phase inversion means a change of emulsion type from
o/w to w/o or vice versa. This technipue is used to
prepare stable and fine emulsions. Phase inversion can
be obtained by two ways …

1. Changing the chemical
nature of emulsifier
 For instance ,an o/w emulsion is prepared using sodium
sterate . Then calcium chloride is added to form
calcium sterate, which is oil soluble. Therefore, oil
phase becomes the continous phase and w/o emulsion is
produced….
 Example- white liniment

2. Altering the phase
volume ratio
 In this method, o/w type of emulifier is mixed with an
oil and then a small amount of water is added . Since
the volume of water is small compared to the oil, w/o
emulsion will be formed. As more water is added slowly,
the inversion point is gradually reached and the water
as well as emulsifier envelop the oil to small globules
yielding an o/w emulsion.

Emulsions are evaluated for their physical and
chemical stabilities.
a) Chemical stability study involves the study of
degradation of active drugs, emulsifiers
preservatives, anti-oxidants etc.
b) Physical stability study indicates the retaining of
the integrity of the dosage form during shelf life.
An emulsion is physically stable, if it can restore its
initial properties on moderate shaking.

Methods of Evaluation
of physical stability
1. Extent of Phase Separation
2. Globule Size Distribution
3. Accelerated Stability Studies –
Centrifugation
4. Microwave Irradiation

Extent of Phase Separation
 The practical and commercial aspect of
stability is the study of phase separation.
 This is a quick method and can be applied
for poorly formed and rapidly breaking
emulsions.
 Separation of phases is visible after a
definite period of time, though the signs
of instability (creaming and coalescence)
begin quite early.

Globule Size Distribution
 An early sign of instability is indicated by the
appearance of bigger size globules.
 This is due to aggregation and coalescence of small
globules from time to time, during storage.
 Therefore, microscopic examination of globule size
distribution analysis is an useful tool to evaluate the
physical stability.
 The method is similar to the procedure described for
particle size analysis by optical microscopy in
micromeritics.

 Globule size (diameter) in micrometers can be plotted
on the x-axis and the frequency (number of globules of
each size) on y-axis .
 The specific surface of the globules gives better
correlations than the globule size distribution regarding
physical stability.
 Immediately after manufacture, the emulsion exhibits
active coalescence stage for some period.
 During this period, the emulsion gets stabilised and is
relieved of the stresses induced in the preparation.
 Beyond this period, the emulsion remains stable on
extended storage.

Accelerated Stability Studies –
Centrifugation
 Normally, flocculation and creaming are slow processes.
 However, these processes can be hastened by inducing
stress conditions using ultracentrifuge.
 The emulsions are subjected to different centrifugal
speeds (2000-3000 rpm) at room temperature and the
separation of phases is observed at different time
periods.
 A bad emulsion,normally,separates the oil instantly.
 A good emulsion does not exhibit detectable separation
of oil phase, until certain time period, i.e., induction
period.

Microwave Irradiation
 The emulsion is exposed to microwave
irradiation.
 Then the surface temperature of the
emulsion tends to be highest and the
temperature gradient between the
surface and the bottom of the
emulsion must be small for the most
stable emulsion

Transparent emulsion is may be defined as a
system of water , oil and amphiphiles,
which is a single optically isotropic and
thermodynamically stable liquid solution.
Transparent emulsion contain globules of the
size about 0.01um. Droplets of such
dimensions cannot refract light, and as a
result, globules are invisible to the naked
eye. Therefore transparent emulsion is
also known as Microemulsions.
Example are etoposide and methotrexate.

APPLICATION OF
EMULSIONS
 O/W emulsions are convenient preparations for
the oral administration of unpalatable oils or oily
solutions of drugs with unpleasant tastes.
 O/W emulsions are also used as a dosage form for
the intravenous administration of oils and fats
with high calorie contents to patients who cannot
ingest food byother means.
 Several oily drugs are prepared in the form of
emulsions.
 Milk which is an important constituent of over
diet is an emulsion of liquid fats in water.

APPLICATION OF
EMULSIONS
 The cleansing action of ordinary soap
for washing clothes, crockery is based
upon the formation of oil-in-water
emulsion.
 Emulsions of both types o/w and w/o
are used extensively in pharmaceutical
preparations for external use and in
cosmetic preparations.

RHEOLOGIC PROPERTIES
OF EMUlSION
 Rheology : Rheology means study of
flow of liquid or soft solid. Emulsion
are evaluated for its flow behavior.
 Performance of the emulsion depend
on flow properties.
a. Removal of an emulsion from a bottle
or tube.
b. Flow of an emulsion through a
hypodermic needle.

c. Spreadability of an emulsion on
the skin.
d. Stress induced flow changes
during manufacture ( milling etc).7
Dilute emulsion exhibit Newtonian
flow and the comparison of flow
curves among different batches is
easy.
concentrated emulsion owing to
their non-Newtonian flow.

Multipoint viscometers such as cone
and plate or cup and bob type can
be employed for evaluation.
Different factors influencing the
viscosity of an impulsion have been
discussed in earlier section.
Type of flow based on phase volume
ratio.

PHASE VOLUME RATIO
5 % - Newtonian flow
50 % - pseudo plastic
74% - plastic flow or phase
inversion (abrupt changes in the
behaviour)
An optimum level of viscosity is to
be identified for maximum physical
stability.

PREPARATION OF IMULSION
Selection of the important
components.
Selection of oil phase:-
A variety of substances have
been used for oil phase.
EXAMPLES :-
fixed oil (corn soya bean,

 Aliphatic hydrocarbons ( liquid
paraffin, turpentine oil etc
Beeswax, spspermaceti.
 Glycerides (long and medium chain
)
Fatty acids and alcohols.
Many of them prone to oxidation.
Therefore, it is necessary to
include suitable antioxidant in the
formulation.

SELECTION OF OIL PHASE
IS DETERMINED BY SEVERAL FCTORS
a) Desired physical properties of the
product.
b) Potential toxicity of the oil to the
route of administration.
c) Solubilityof active product in the oil.
d) Consistency of the product quilities.
e) Any possible incompatibilities.

Selection of aqueous phase:-
Mostly water is used.
Sometimes,the organoleptic features
of the emulsion demand the need of
adding sweeteners and flavouring
agent.
Sensitivity of skin and nature of
adsorption determine the pH of
aqueous phase.
In addition electrolytes and
preservatives are included.

Optimum volume of aqueous phase
should be decided.
Appropriate phase volume ratio
should be selected.

Selection of emulsifying agent :-
Selection of emulsifying agent is also
based on the internal use.
For internal use :- Non ionic and
water soluble emulsifying agent are
chosen.
For external use :- Both ionic and
nonionic emulsifying agent are
employed.

PHASE INVERSION
 Phase inversion means the change of one
type of emulsion into the other type i.e., oil
in water emulsion change into water in oil
and vice versa.
 It may be due to following reasons:-
 By the addition of an electrolyte
 By changing the phase -volume ratio
 By temperature change
 By changing the emulsifying agent.

 The phase inversion can be minimized by
keeping the concentration of disperse phase
between 30 to 60%, storing the emulsion in a
cool place and by using a proper emulsifying
agent in adequate concentration.

Preparation of emulsions
and
Rheological properties of emulsions

Preparation of emulsion
 Before attempt to prepare an emulsion ,it is necessary to select an
important components .
 Selection of oil phase :
A variety of substances used for oil phase include fixed oils ,bees wax,
glycerides, fatty acids and alcohols. Selection of oil phase is
determined by several factors :
(a) desired physical properties of product
(b)potential toxicity of oil to route of administration
(c) solubility of active product in the oil
(d)consistency of product qualities
(e) incompatibilities

 Selection of aqueous phase
Mostly water is used ,sometimes emulsion demand the need of adding
sweeteners and flavouring agents. Sensitivity of skin and nature of
adsorption determine the pH of aqueous phase . Also electrolytes and
preservatives are included ,thus optimum volume of aqueous phase is
selected
 Selection of emulsifying agent
An emulsifying agent is selected on the type of emulsion required.
Selection of emulsifying agent is also based on the use . For internal use
, non ionic and water soluble agent is chosen. For external use ,both
ionic and non ionic agents are employed . It is better to avoid
emulsifying agent of natural origin because they support microbial
growth.
 Physical stability considerations
The rheological character of an emulsion is important in stabilising it
against creaming and viscosity of medium also taken under
consideration

Small scale preparation
 The mortar and pestle is simple and inexpensive equipment used for
small scale production of emulsion . It is used for batch process. These
emulsions are prepared by emulsifying agents such as acacia and
tragacanth .The methods used in small scale preparations :
 Wet gum method
 Dry gum method
 Forbes bottle method

Large scale preparation
 The large scale preparation of emulsion is carried out by three
methods
 Emulsification by Vapourization
 Emulsification by Phase inversion
 Low energy emulsification
The oil and the water phases containing hydrophobic and hydrophilic
components are heated separately in large tanks. when waxes are
present , both phases must be heated above the highest melting point
of any component present . One phase is pumped into tank containing
second phase . Agitation is provided during addition . After cooling the
emulsion is homogenized. Considerable amount of energy is expended
for mixing and heating.

Mechanical equipments for emusification
 Mechanical stirrers
 Propeller type mixers
Turbine mixers
Homogenizers
 Colloid mills
 Ultrasonifiers

Silverson Mixer – Emulsifier
Principle : Silverson mixer produces high intense shearing force and
turbulence by use of high speed rotors . This causes turbulence that
results in fine emulsion . Circulation of material takes place through
the head by suction produced in inlet at the bottom of head .
Construction : It consist of long supporting columns connected to the
motor which give support to head . The central potion contains shaft
which is connected to motor and other end to head . The head carries
turbine blades ,these blades are supported by mesh which furthur
enclosed by cover with openings

Working : The emulsifier head is placed in the vessel containing immiscible liquids .
When the motor is started the shaft rotates the head which then rotates the blades
at very high speed . This creates pressure difference . Then liquids are sucked from
the center of base and subjected to intense mixing . Centrifugal force expel the liquid
with great force through the mesh . This circulation of mixture ensure rapid break
down of bigger globules into smaller globules.

Colloid mill
Uses : Silverson mixer is used for preparation of emulsions and creams
of fine particle size .
Advantages : It is available in different sizes to handle the liquids
from few millimeters to several thousand litres . It can be used for
batch operation and also for continuous operation .
Disadvantages : There is a chance of clogging of pores of mesh.
Principle : Colloid mill is based on the
principle that the coarse emulsion is
intensely sheared in a narrow Space
between the fast moving rotor and
stator for a short period to get a fine
emulsion .
The coarse particles are broken down into
smaller particles due to shear .

Construction : Colloid mill consist of two steel discs having a very
small clearance between them . The clearance between rotor and
stator is adjustable ,usually from 0.001 and upward . During milling ,
heat is generated and thus cold water circulation is provided . A
hopper is provided for feed inlet and discharge pipe is also provided to
recycle the discharge .
Working : Materials for emulsion are
placed in hopper or after cooling the
emulsion mixture is passed between
the rotor and stator . In this process ,
tremendous shearing action is
produced ,which results in formation
of fine dispersion of uniform size .
this process is repeated until the
desired size of dispersion is obtained.
then product is packed .

Ultrasonifiers – Rapisonic
Homogenizer
Uses : Colloid mill is used for preparing colloidal dispersions,
emulsions and ointment . Particle size as small as 3 um can be
obtained .
Advantages : Colloid mill can be sterilized , so a sterile product can
be obtained .
Disadvantages : Heat is generated during milling . Hence ,water
circulation is provided for lowering the temperature .
It is not useful for dry milling .
Principle : when a liquid is subjected to ultrasonic vibrations , alterna
regions of compression and rarefactions are produced in the liquid .
Cavities are formed in the region of rarefaction , which collapse in the
region of compression . This results in generation of forces for
emulsification

Construction : It consist of a pump driven by motor. It is connected with an
inlet tube and outlet tube for discharge for a fine emulsion . The head
consists of a flat jet for liquid inlet. Facing the jet , a thin blade is present
with edges facing each other .This blade vibrates at its natural frequency of
30 kilohertz.
Working :Coarse emulsion is pumped
into one end of a tube . A powerful
stream of liquid is forced through the
jet. Liquid than causes the vibration
of blades. The streaming liquid than
produces oscillations above the sonic
range . During this the mixture
experience alternate compression
and rarefaction . In the region of
rarefaction , cavities are formed .
because of external pressure , the
cavities collapse violently .

Thus sufficient turbulence is created which is capable of causing
dispersion of phases . Thus a fine emulsion is produced .
Advantages : It can be used for batch process or in continous process
by placing in pipeline .
It has capacity to produce dispersed globules of one micron size.
It reduces the concentration of emulgents in emulsion.
Its capacity ranges from 20 to 500 litres per minute .
Heat is not generated during mixing thus thermolabile substances can
be emulsified .
Disadvantages : Rapisonic homogenizer is useful only with liquids of
low viscosity

Propeller Mixers
A propeller normally contains number of blades
Propellers may be right handed or left handed ,
depending on direction of slant of their blades.
The degree of agitation is controlled by
propeller rotation but pattern of liquid flow
and resultant efficiency of mixing is
controlled by type of impeller ,
its position in container , the presence of baffles ,
and the shape of container .
These stirrers are used when vigorous agitation is
needed , extremely small droplets are needed

Turbine type of Mixers
When vigorous agitation is required or
viscosity is more , turbine type mixers can
be used

Rheologic properties of
emulsions
 Emulsions are evaluated for its flow behaviour . The following factors
are considered for the overall performance of an emulsion :
 1 Removal of an emulsion from bottle or tube
 2 Flow of emulsion through a hypodermic needle
 3 Spreadability of an emulsion on the skin
 4 Stress induced flow charges during manufacture
 In general dilute emulsions exhibit Newtonian flow but analysis
become complicated incase of concentrated emulsions owing to their
non – newtonian flow .
 The flow behaviour of emulsion is mainly affected by its viscosity
which may include viscosity of continous phase , viscosity of dispersed
phase , nature and concentration of emulsifying agent.

 Viscosity of continous phase : It is well documented that a direct
relationship exists between the viscosity of continous phase and
viscosity of emulsion . Syrups and glycerol which are used in oral
emulsions as sweetening agents will increase the viscosity of
continous phase . This may increase the density difference between
the two phases and thus accelerates creaming . Hydrocolloids are
used as emulsifiers in o/w emulsion and they also increase the
viscosity of continous phase but doe not alter the density of the
phase.
 Viscosity of dispersed phase : this factor may not significant effect
on total emulsion viscosity . It is possible that a less viscous
dispersed phase would be deformed to a great extent than a more
viscous phase during shear thus total interfacial area may increase
and thus may affect the viscosity of emulsion .
 Nature and concentration of emulsifying agent : it has already
shown that hydrophilic colloids will increase the viscosity of
continous phase of o/w emulsion thus concentration of this type of
emulgent increases the viscosity of product .

 A rough guide regarding the type of flow can be obtained based on
phase volume ratio . They are :
Phase volume ratio Type of flow
5% newtonian
50% pseudo plastic
74% plastic flow or phase
inversion
An optimum level of viscosity is to be identified for maximum
physical stability

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