COLLEGE OF PHARMACEUTICS II

PHARMACY (PHT 312)

Dr. Mohammad Javed Ansari, PhD.

Contact info:
javedpharma@gmail.com
Deptt of Pharmaceutics, COP, PSAU, Al-kharj
 OBJECTIVES OF THE LECTURE
 At the end of this lecture, you will be aware of:
 What are disperse systems?
 What are various types of disperse systems?
 What are emulsions?
 What are various types emulsions?
 Why emulsions are thermodynamically unstable?
 What are various stability problems?
 How emulsions are stabilized?
 What are emulsifying agent / emulgents?
 What are various types of emulgents?
 How emulgent stabilize the emulsion?
 What are advantages / disadvantages of emulsions?
 How emulsions are prepared?
Disperse systems
 Emulsion
 BIPHASIC LIQUID DOSAGE FORM consisting of one liquid
phase dispersed as globules/droplets (dispersed phase or
internal phase) within a second immiscible liquid phase
(continuous phase/ external phase).
 Thermodynamically unstable because of immiscible phases.
 These system are stabilized by using emulsifying agents.
 Emulsifying agents Reduce interfacial surface tension

Dispersed phase

Continuous phase
 THEORY OF EMULSIFICATION

What happens when 2 immiscible liquids are agitated together?

One of the liquids is dispersed as small droplets in the other.
But after a while !
The liquids separate rapidly into
two clearly defined layers
WHY?
 A fine dispersion of oil and water leads to an enormous
increase in the interfacial area.
 This is associated by an increase in the interfacial free
energy also known as surface free energy.
 This phenomenon leads to the system is thermodynamically
unstable.
 The high interfacial free energy favors a reduction of
interfacial area by causing droplets to coalesce. Therefore
separation of phases takes place.
 THEORY OF EMULSIFICATION
SURFACE FREE ENERGY: The work W required to create a
unit area of surface is known as SURFACE FREE ENERGY/UNIT
AREA (ergs/cm2).
Work W = F × d (force multiplied by distance ), γ =F/2L,
(γ surface tension, is the force per unit length) F= γ × 2L
W = γ × 2L × d (since 2L × d is equal to the increase in surface area ΔA).
W = γ ΔA (ΔA is increase in area for a finite work.

∆E = OW X ∆A

Thus the greater the area A of interfacial contact between the

phases, the greater the free energy.
SURFACE FREE ENERGY is equivalent to the surface tension γ.
Therefore to decrease surface free energy we can decrease
surface tension by adding surfactants/emulgent or emulsifying
agents.
 THEORY OF EMULSIFICATION: How Emulgents Work?
Emulsifier – The Stabilizer

Lipophilic Tail & Hydrophilic Head

Lipophilic tails align with oil

Hydrophilic heads align with water
Emulsifying agents stabilize emulsions by 3 mechanisms:
1. Reduction of interfacial tension.
2. Formation of a rigid interfacial film-
mechanical barrier to coalescence

3. Formation of an electric double layer-

electric barrier to approach of particles.
THEORY OF EMULSIFICATION: How Emulgents Work?

1. Reduction of interfacial tension.

∆E = SL * ∆A
2. Formation of a rigid interfacial film-mechanical barrier to coalescence.
If the concentration of the emulsifier is high enough, it forms a
rigid film between the immiscible phases, which hinders
mechanically the coalescence of the emulsion droplets.
3. Formation of an electric double layer- electric barrier to coalescence.
In case of an ionic surfactant, the
hydrocarbon tail is dissolved in the oil +
++
+
droplet, while the ionic heads are + +
facing the continuous aqueous phase. + +
++ +
+ +
As a result, the surface of the droplet is ++
charged. This creates a repulsive effect
between the oil droplets and thus
hinders coalescence.
 THEORY OF EMULSIFICATION:
HOW EMULSIONS ARE STABILIZED?
 CLASSIFICATION OF EMULSIONS
 Based on nature of dispersed phase
 Oil in Water (O/W): Oil droplets dispersed in water.
 Water in Oil (W/O): Water droplets dispersed in oil.
 Based on size of dispersed phase /droplets.
 >1000 nm Macroemulsions
 10 – 200 nm Microemulsions
 Based on Number of dispersed phase: Multiple emulsion
 W/o/w (water in oil in water): Small water droplets are
enclosed within larger oil droplets which are themselves then
dispersed in water
 O/w/o (oil in water in oil): Small oil droplets are enclosed within
larger water droplets which are themselves then dispersed in
oil phase
CLASSIFICATION OF EMULSIONS
 Oil in Water – O/W
 Dispersed phase / Internal phase = OIL
 Dispersion medium/ continuous phase /External phase = WATER
 Advantages
 Easiest to formulate
 disperses more easily
 has consistent pH
 Least expensive
 Best feel – cooling effect
 Disadvantages
 Less oil delivered
 Not as effective for dry skin

 Not water-resistant
Examples: Hair conditioners, Sunscreen, vanishing cream, Wrinkle
Creams, Mayonnaise, milk, cream and butter.
 Water in Oil – W/O
Dispersed phase / Internal phase = WATER
Dispersion medium/ continuous phase /External phase=WATER
 Advantages
 Waterproofing possible
 Most effective for dry skin

 Better stability

 Disadvantages
 Oily, tacky feel
 More expensive
Examples: COLD CREAMS
 Multiple Emulsions
 Multiple phases
 Oil in Water in Oil (O/W/O)
 Water in Oil in Water (W/O/W)
 Advantages
 More effective than Oil in Water
 Less greasy than Water in oil
 Time release, active delivery possible
 Disadvantages
 Difficult to manufacture
 Not always stable
 PHARMACEUTICAL APPLICATIONS OF EMULSION
 Masking of unpleasant taste:
Most important application of emulsion is for masking the
disagreeable taste of oily liquids by formulating them as o/w
emulsions. For e.g. some vitamins.
 Increase the absorption:
Emulsions of oils like liquid paraffin and olive oil enhance the
rate and extent of their absorption from the alimentary canal
due to fine state of subdivisions.
 Topically applied:
 Medicinal agents that are irritating to the skin are less
irritating if present in the internal phase of emulsion.
 Cold cream and vanishing creams are a emulsion which
are used externally.
 More acceptable than greasy products (ointments).
 PHARMACEUTICAL APPLICATIONS OF EMULSION
 Parenteral administrations
Emulsions have been used for the intravenous administrations
of lipid nutrients.
w/o emulsions have been employed to disperse water soluble
antigenic materials in mineral oil for intramuscular depot
injection.
 Aerosol
Emulsification is used in aerosol to produce foams
 Prolonged Action
These products can also be used for the prolonged release of
drugs that are incorporated into the internal aqueous phase.
 Formulation aspects:
Elements of the Formula
 Formula Components
 Oil Phase
 Hydrophobic materials: Oils, fats, lipids
 Affects viscosity, spread,

 Aqueous phase
 Extracts, colorants
 Humectants

 Thickeners

 Emulsifiers
 Holds it all together
 Types of Emulsifying
agents

Synthetic Natural

Anionic Cationic AMPHOTERIC Nonionic

Alkali soaps Quaternary Aminoacids Glycerol

esters
ammonium
compounds
Sorbitan
Amine soaps Betains esters
Cetrimide
Sulphated
comp.
Lecithin Polysorbates
Cetylpyridinium
chloride
Higher fatty
Corboxylate alcohol
d compds
Benzalkonium chloride
Types of Emulsifying agents
e.g. Sodium stearate
Sodium lauryl sulfate
Triethanolamine stearate

Eg. Cetrimide, Cetylpyridinium chloride

Benzalkonium chloride

Eg. Betains,
Aminoacids,
Lecithin

Cetyl and stearyl alcohols

Glyceryl monostearate
Sorbitan esters of fatty acids (Spans)

Polyethylene glycol derivatives of the sorbitan esters (Tweens)

 Non-ionic surfactants

Most non-ionic surfactants are based on:

 A fatty acid or alcohol (usually with 12-18 carbon atoms), the
hydrocarbon chain of which provides the hydrophobic part.

 An alcohol (-OH) and/or ethylene oxide group (-OCH2CH2-) which

provide the hydrophilic part of the molecule.

Advantages
 They have greater degree of compatibility than do anionic and
cationic emulgents.
 Less sensitive to changes in pH & electrolytes.
 They are very useful for parenteral and oral administration because
of their low toxicity and irritancy.
 Non-ionic surfactants
Sorbitan esters of fatty acids (Spans)
 Sorbitan is esterified with lauric, palmitic, stearic or oleic fatty acid.
 Variations in the type of fatty acid produce different Spans:
Span 20 with lauric acid (sorbitan monolaurate)
Span 40 with Palmitic acid (sorbitan monopalmitate)
Span 60 with stearic acid (sorbitan monostearate)
Span 80 with oleic acid (sorbitan monooleate)

Polysorbates (Tweens)
 Polyethylene glycol derivatives of the sorbitan esters (Polyoxtethylene
sorbitan ester of fatty acids).
 Variations in the type of fatty acid produce different tweens chain with
different oil and water solubility, (Tween 20, 40, 60 and 80).
Advantages of tweens:
o Compatible with other types of surfactants.
o Stable to heat, pH change and electrolytes.
o Low toxicity, for oral and parenteral preparations.
 Disadvantages:
o Unpleasant taste.
o Inactivate some preservatives as parabenze by complexation
 NATURAL EMULSIFIERS
Only acacia is regarded as primary emulsifier. The rest are used mainly as
emulsion stabilizer. They produce o/w emulsions.

A- Acacia: Its mucilage allow the oil to be sheared into finely divided globules.
However acacia is not viscous enough to prevent rapid rise of globules
(creaming) thus sometimes thickening agents e.g. agar or tragacanth are
added.

B- Tragacanth & Sodium alginate: The emulsifying ability is due to the high
viscosity of its mucilage.

C- Polysaccharides: They form at the oil/water interface a multi-molecular layer

that act as a barrier to coalescence.
D- Starch:Is a poor emulsifying agent. It acts by increasing the viscosity of
continuous phase. It is used for preparation of enemas containing oil.
 Hydrophilic-Lipophilic Balance (HLB) System
 Emulsifiers / Surfactants are characterized according to the "balance"
between the hydrophilic ("water-loving") and lipophilic ("oil-loving")
portions of their molecules.
 The hydrophilic-lipophilic balance (HLB) number indicates the polarity of
the molecules in a range of 1-40, with the most commonly used
emulsifiers having a value between 1 and 20.
 The HLB number increases with increasing hydrophilicity.
 According to the HLB number, surfactants may be utilized for different
purposes:

Function HLB Range

Antifoaming agent 1-3
Emulsifier, (w /o) 3-6
Wetting agent 7-9
Emulsifier, (o/ w) 8-18
Detergent 13-15
Solubilizer 15-18
 Emulsifiers – HLB system
 HLB tells about varying degrees of non-polar & polar character.
Less polar
(low HLB)

More Polar
(High HLB)
 Specific oils need emulsifier with specific HLB (polar/non-polar
character) to be effectively emulsified.
 Emulsifiers should have similar HLB values to that of the respective
oils in order to achieve maximum stabilization.

Common Oils used and

the HLB needed to
Create an emulsion
 Hydrophilic-Lipophilic Balance (HLB) System
 The desired HLB numbers can also be achieved by mixing lipophilic and
hydrophilic surfactants.
 William Griffin devised HLB System to calculated amount of emulsifier
to get the desired HLB.

 Advantage of HLB system:

 Gives stable emulsion.
 Works best with nonionic surfactants.
 Disadvantage:
.
 HLB is only a good approximation.
 Doesn’t always work.
 WHAT ARE OTHER ADDITIVES IN EMULSIONS?
Preservatives
Antioxidants
Humectants
Density modifiers
Buffers
Flavors and sweetening agents
 Preservatives
 Low o/w partition coefficient.
 Free from toxicity, color, odor and taste.
 Effective in present of other ingredients and in wide range
of pH and temperature.
Types of preservative
Parahydroxybenzoic acid esters:
Methyl, ethyl, propyl, butyl esters are effective at pH 7-9.
 Organic mercurial compounds:
Phenyl mercuric nitrate and acetate effective in emulsions
containing non-ionic emulgents.
 Organic acids:
Used in acidic pH (Benzoic and Sorbic acids).
 Preservatives……
Quaternary ammonium compounds:
Cetrimide Emulsifying and preservative agent ineffective
against gram –ve bacteria and bacterial spores.
 Chlorocresol:
For external preparations, its activity reduce at pH and in
presence of vegetable oils.

Humectants
• Propylene glycol, glycerol and sorbitol (5%).
• Reduce the evaporation of water from opened package or from the
skin.
• At high concentration they cause dehydration and remove moisture
from the skin.
 Antioxidants
Oxidation of vegetable oils cause its rancidity with unpleasant odor
and appearance
They are classified into:
 True Antioxidants (oil soluble)
E.g. Butylated hydroxy anisole, Butylated hydroxy toluene,
L-tocopherol (Vitamin E).
they capable of involvement in free radical process, protecting the
oil from involvement.
 Reducing agents:
E.g. Sodium metabisulfate, Cystein HCl , Ascorbic acid (Vitamin C).
EDTA as chelating agent retard the oxidation reaction as it
chelate metal ions that catalyze oxidation process.
 Methods of Emulsion Preparation:

On a small scale, emulsions may be prepared using:

• A dry porcelain mortar and pestle.
• A mechanical blender or mixer.
• A simple prescription bottle.
On a large scale
Mechanical stirrer
High speed impeller in large volume mixing
tanks may be used to form the coarse
emulsion.
Homogenizers
The dispersion of two liquid is achieved by
forcing their mixture through a small inlet
orifice at high pressure.
colloid mill
Colloid mill operate on the principle of high
shear, which is generated between the rotor
and the stator of the mill.
 Methods of Emulsion Preparation:
Lab methods used by the community pharmacist.
1- The continental or dry gum method
the emulsifying agent (usually acacia) is mixed with the oil before
the addition of water.
2- The English or wet gum method
the emulsifying agent is added to the water. (In which It Is soluble)
to form a mucilage, and then the oil is slowly incorporated to form
the emulsion
3- The bottle or the Forbes bottle method
The bottle method is reserved for volatile oils or less viscous oils.
Powdered acacia + 2 part of oil are placed in a dry bottle and the
mixture is thoroughly shaken.
A volume of water approximately equal to the oil is then added in
portions, the mixture being thoroughly shaken after each addition
the primary emulsion thus formed may be diluted to the proper
volume with water.
 Methods of Emulsion Preparation:
• Bancroft's rule:
• Emulsion type depends more on the nature of the emulsifier
than on the relative proportions of oil
• or
• water present
• or
• the methodology of preparing emulsion.

• 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
oil than in water (Low HLB surfactants).
• The order of addition of the phases
• W O + emulsifier W/O
• O W + emulsifier O/W.
 Tests for Identification of Emulsion Type

Miscibility tests with oil or water

The emulsion will only be miscible with liquids that are miscible
with its continuous phase.

Conductivity measurements
Systems with aqueous continuous phases will readily conduct
electricity, whereas systems with oily continuous phases will not
since most oils are poor conductors
 Staining tests
If a water-soluble dyes is added in an o/w emulsion the emulsion
takes up the color uniformity, phase is continuous phase.
Conversely if the emulsion is w/o type and dye being soluble in
water, the emulsion takes up the color only in the dispersed phase
and the emulsion is not uniformly colored.

O/W emulsion W /O emulsion

Fluorescence Method
Many oils fluoresce under ultraviolet
light. Thus, if the whole field
fluoresces under fluorescent light
microscope, the emulsion is wl o, if,
on the other hand, only a few
fluorescent dots are evident, the
emulsion is o/w. O/W emulsion W /O emulsion
Wetting of Filter Paper Method
This method depends on the respective abilities of oil and water to
wet filter paper. A drop of the emulsion is placed on a piece of filter
paper; if the liquid spreads rapidly, leaving a small drop at the center,
the emulsion is o/w. If no spreading occurs, the emulsion is w/o.
 Stability of Emulsions
What are the characteristics of a stable emulsion?
A stable emulsion is one in which:
-dispersed globules retain their initial character
-and remain uniformly distributed throughout the
continuous phase.
Thus change in number of dispersed globules
Change in size of globules
Change in globule size distribution (polydispersity index)
and change in viscosity means unstable emulsions.
Physical Instability of emulsions

Deptt of Pharmaceutics, COP, SAU, Al-

kharj
Physical Instability: Creaming and Sedimentation
 Creaming and Sedimentation:
 This process results from external forces, usually
gravitational or centrifugal.
 When such forces exceed the thermal motion of the
droplets (Brownian motion), a concentration
gradient builds up in the system such that the larger
droplets move more rapidly either to the top
resulting in CREAMING (if their density is less than
that of the medium)
 or to the bottom resulting in SEDIMENTATION (if
their density is greater than that of the medium) of
the container.
 Physical Instability: Creaming & sedimentation
Creaming and sedimentation results temporary changes of emulsion into
two regions, one of which is richer in the disperse phase than the other e.g.
the creaming of milk, when fat globules slowly rise to the top of the
product.
Creaming and sedimentation are reversible process.
Velocity of the creaming and sedimentation is governed by Stokes’ law

2 r2 ( - o) g
V=
9
g = gravity constant
r = radius of the dispersed globules
 = viscosity of the external phase
 = density of the internal phase
o= density of the external phase
v = velocity of sedimentation of the dispersed spherical particles
 From this this law it is clear that velocity is directly proportional to
density difference between the both phase, and radius of the globules.
 Inversely proportional to viscosity of the external phase.
B- Coalescence (Breaking, Cracking)
Process of thinning and disruption of the liquid
film between the droplets, with the result that
fusion of two or more droplets occurs to form
larger droplets.
Cracking or coalescence of an emulsion leads
to the separation of dispersed phase as a layer.
Cracking is a irreversible process (permanent loss) .
Preventing Coalescence (Breaking, Cracking)
The coalescence of oil globules in an o/w emulsion is
resisted by the presence, of a mechanically strong
adsorbed layer of emulsifier around each globule.

This is achieved by the presence of either a

condensed mixed monolayer of lipophilic and
hydrophilic emulgents, or a multimolecular film of a
hydrophilic material.
Physical Instability: Flocculation & Ostwald ripening

 Flocculation : Aggregation of the droplets (without

any change in primary droplet size) into larger units.
 Flocculation occurs when there is not sufficient
repulsion to keep the droplets apart at distances
where the van der Waals attraction is weak.
 Ostwald Ripening (Disproportionation) : Aggregation
of the droplets with change in primary droplet size.
 With emulsions which are usually polydisperse, the
smaller droplets will have a greater solubility when
compared to larger droplets (due to curvature
effects).
 With time, the smaller droplets disappear and their
molecules diffuse to the bulk and become deposited
on the larger droplets.
 Physical Instability: Inversion of Emulsions
(Phase inversion)
O/W W/O
 Nature of emulsifier: Making the emulsifier more oil soluble tends
to produce a W/O emulsion and vice versa. (Bancroft's rule)

 Phase volume ratio

Oil/Water ratio  W/O emulsion and vice versa.

 Temperature of the system:  Temperature of O/W makes the

emulsifier more hydrophobic and the emulsion may invert to W/O.

 Addition of electrolytes and other additives: Addition of Strong

electrolytes to O/W (stabilized by ionic surfactants) may invert to
W/O
Example. Inversion of O/W emulsion (stabilized by sodium cetyl
sulfate and cholesterol) to a W/O type upon addition of polyvalent Ca.
 2- Chemical Instability of Emulsion
1) Chemically incompatibility of the emulgent system with the active
agent and with the other emulsion ingredients
• Ionic emulsifying agents are usually incompatible with materials
of opposite charge. i. e. anionic and cationic emulgents .
• Addition of electrolyte may cause salting out of the emulsifying
agent or phase inversion e.g. sodium soap stabilize o/w emulsion
so when a divalent electrolyte such as CaCl2 is added it may form
the calcium soap, which stabilize a w/o emulsion.
• Emulgents may also be precipitated by the addition of materials in
which they are insoluble e.g. precipitation of hydrophilic colloids
by the addition of alcohol.
• Changes in pH may also lead to the breaking of emulsions.
Sodium soaps may react with acids and produce the free fatty
acid and the sodium salt of the acid. Soap-stabilized emulsions
are therefore usually formulated at an alkaline pH.
 2- Chemical Instability of Emulsion

2) Oxidation

Many of the oils and fats used in emulsion formulation are of

animal or vegetable origin and can be susceptible to oxidation
by:
 Atmospheric oxygen or .
 By the action of microorganisms.

The resulting rancidity is manifested by the formation of

degradation products of unpleasant odour and taste.

This can be controlled by the use of:

 Antioxidants.
Antimicrobial preservatives.
 2- Chemical Instability of Emulsion….
3) Microbiological Contamination
Microbial contamination may causes:
 Gas production.
 Colour and odour changes.
 Hydrolysis of fats and oils.
 pH changes in the aqueous phase.
 Breaking of the emulsion.
Why it happens?
 Some of the hydrophilic colloids (emulsifying agents) may provide a
suitable nutritive medium for microorganisms.
 Most fungi and many bacteria will multiply readily in the aqueous phase
of an emulsion.
 o/w emulsions tend to be more susceptible to microbial spoilage than w/o
products, why? In w/o emulsions the continuous oil phase acts as a
barrier to the spread of microorganisms throughout the product, and the
less water there is present the less growth there is likely to be.
 Therefore an antimicrobial agent must be added.
 2- Chemical Instability of Emulsion….
4) Adverse Storage Conditions
Increase in temperature will causes:
 An increase in the rate of creaming, due to a fall in
apparent viscosity of the continuous phase.

 increased kinetic motion of the dispersed droplets thus the

number of collisions between globules will increase

 The emulsifying agent at the oil/water interface will result

in a more expanded monolayer, and so coalescence is more
likely.

 Certain macromolecular emulsifying agents may be

coagulated.

Decrease in temperature may cause:

Precipitation of certain emulgents.
 Stability Testing of Emulsions
1) Macroscopic Examination
Examination of the degree of creaming or coalescence occurring
over a period of time.
This is carried out by calculating the ratio of the volume of the
creamed or separated part of the emulsion and the total volume.
2) Globule Size Analysis
Microscopic examination - Coulter counter - laser diffraction sizing
are most widely used to determine the mean globule size as an
increase with time is a sign for coalescence.
3) Viscosity Changes
Any variation in globule size or number or in the orientation or
migration of emulsifier over a period of time may be detected by a
change in apparent viscosity.
In order to compare the relative stabilities of similar products it is
often necessary to speed up the processes of creaming and
coalescence by temperature cycling or centrifugation.
 Emulsion
suitable for
intravenous
injection.

Balm: Water in oil emulsion

Emulsions Sodas: Oil in Water emulsion

Milk: Oil in Water

emulsion

Dodecane droplets in a Mayonnaise: Oil in

continuous phase of Water emulsion
water/glycerol mixture.
Emulsions encountered in everyday life!

Pesticide Asphalt Skin cream

Metal cutting oils Margarine Ice cream

 THANK YOU FOR
ATTENTION

GOOD LUCK ..

November 2, 2018 Deptt of Pharmaceutics, COP, SAU, Al-kharj