EMULSIONS

Definition:
An emulsion is a thermodynamically unstable system consisting of at least two immiscible
liquid phases one of which is dispersed as globules in the other liquid phase stabilized by a third
substance called emulsifying agent.
An emulsion is an intimate mixture of two immiscible liquids that exhibits an acceptable shelf
life near room temperature. Most emulsion will have droplets with diameters of 0.1 to 100μm.
Internal Phase or External Phase in Emulsions:
The dispersed liquid is known as the Internal or Discontinuous phase. The droplet phase is
called the dispersed phase or internal phase whereas the dispersion medium is known as the
External or Continuous phase. The liquid in which droplets are dispersed is called the external
or continuous phase.
Composition of Emulsion:
1. AQUEOUS PHASE:
Consists of purified or the ionized water which contains water soluble drug preservatives, coloring
and flavoring agents. If tap water or hard water is used in the formulation it has adverse effect on the
stability of emulsions, particularly those emulsion containing fatty acids and soap as emulsifying
agents.
2. OILY PHASE: The oily phase of an emulsion consists of fixed, volatile or mineral oil which
contains oil soluble vitamins and antiseptics. The oil used in the formation of an emulsion should be
auto-oxidation as well as from microbes.

3. EMULSIFYING AGENTS: It is the component of emulsion which bound the two

immiscible liquids by forming a film around the dispersed globules and makes the emulsion stable.
So, it prevents the two liquids (water and oil) from separating as two distinct layers.
The emulsifying agents are of great importance in any type of emulsion i.e. o/w, w/o, multiple or
micro emulsion. This process is called emulsification.

Advantages of Emulsions:
 A dose of an unpalatable drug may be administered in a palatable liquid Form (e.g. Cod
liver oil, fish oil emulsion).
 An oil-soluble drug can be dissolved in the disperse phase and be successfully administered
to a patient in a palatable form. (e.g. Propofol, diazepam)
 The aqueous phase can be easily flavoured.
 The texture/consistency of the product is improved as the ‘oily’ sensation in the mouth is
successfully masked by the emulsification process.
 Absorption may be enhanced by the diminished size of the internal phase.
 Emulsions offer potential in the design of systems capable of giving controlled rates of drug
release and affording protection to drugs susceptible to oxidation or hydrolysis.
 Emulsions have been used to deliver poorly water-soluble drugs, such as general anesthetics
and anti-cancer compounds, via the intravenous route

Disadvantages:
 Preparation needs to be shaken well before use
  Measuring device needed for administration
 Need a degree of technical accuracy to measure a dose
 Storage conditions may affect stability
 Bulky, difficult to transport and prone to container breakages
 Liable to microbial contamination which can lead to cracking

Classification of Emulsions:
1. BASED ON DISPERSED PHASE:
 Oil in Water (O/W): Oil droplets dispersed in water
 Water in Oil (W/O): Water droplets dispersed in oil

2. BASED ON DIAMETER OF LIQUID DROPLETS:

 Droplets may be 0.5μm in diameter is called macro emulsions (thermo- Dynamically
unstable)
 diameter of droplets is 0.01μm - 0.1μm is called micro emulsions (thermo- Dynamically
stable)

Multiple Emulsions:
 Multiple emulsions are complex poly-dispersed systems where both oil in water and water
in oil emulsion exists simultaneously which are stabilized by hydrophilic and lipophilic
surfactants respectively. In these types of emulsions three phases are present:
 In (water in oil in water) w/o/w emulsion an oil droplet enclosing a water droplet are
suspended in water.
 In (oil in water in oil) o/w/o emulsion a water droplet enclosing an oil droplet are suspended
in oil.
 In these “emulsions within emulsions,” any drug present in the innermost phase must now
cross two phase boundaries to reach the external, continuous phase.
 Whether the aqueous or the oil phase becomes the dispersed phase depends primarily on the
emulsifying agent used and the relative amounts of the two liquid phases.
 Most pharmaceutical emulsions designed for oral administration are of the O/W type;
emulsified lotions and creams are either O/W or W/O, depending on their use.
Theories of Emulsification:
 Several theories have been proposed to explain how emulsifying agents act in producing
the multi-phase dispersion and in maintaining the stability of the resulting emulsion.
 Theory of viscosity
 Fischer theory
 Surface-tension theory
 Oriented-wedge theory
 Plastic or Interfacial film theory
 The most prevalent theories are the surface-tension theory, the oriented-wedge theory,
and the interfacial film theory.

1. SURFACE TENSION THEORY:

 According to the surface tension theory of emulsification, the use of surfactants results in
a reduction in the interfacial tension of the two immiscible liquids reducing the repellent
force between the liquids diminishing each liquid’s attraction for its own molecules.
 Thus, surfactants enable large globules to break into smaller globules, and prevent small
globules from coalescing into larger globules
PLASTIC OR INTERFACIAL FILM THEORY:
 When two immiscible liquids come in contact, the force causing each liquid to resist
breakage into smaller particles is known as interfacial tension. When a high interfacial
tension existed between two liquids emulsification is difficult, and if the tension could be
reduced emulsification facilitated.
 The interfacial film theory proposes that the emulsifier forms an interface between the oil and
water, surrounding the droplets of the internal phase as a thin layer of film adsorbed on the
surface of the drops.
 The film prevents the contact and coalescing of the dispersed phase; the tougher and more
pliable the film, the greater the stability of the emulsion
 Greater is the interfacial tension, less stable will be the emulsion as more attraction of the
dispersed globules experiences lowering of the interfacial tension is important in the initial
formation of an emulsion, but the formation of a protective wedge of molecules or film of
emulsifier is important for continued stability.
HARKIN’S ORIENTED – WEDGE THEORY
 The oriented wedge theory proposes that the surfactant forms monomolecular layers around
the droplets of the internal phase of the emulsion. The theory is based on the assumption that
 emulsifying agents orient themselves about and within a liquid relative to their solubility in
that particular liquid.
 Because surfactants have a hydrophilic or water loving portion and a hydrophobic or water
hating portion (but usually lipophilic or oil-loving), the molecules position or orient
themselves into each phase
 Depending on the shape and size of the molecules, their solubility characteristics, and, thus,
their orientation, the wedge shape theory proposes that emulsifiers surround either oil
globules or water globules.

 An emulsifying agent, having a greater hydrophilic character than hydrophobic character,

will promote oil in water emulsions.
 Conversely, water in oil emulsions result with the use of an emulsifier that is more
hydrophobic than hydrophilic.
 In this theory the surfactant emulsifier molecules are assumed be shaped like wedges;
therefore, it is termed “Oriented wedge” theory.

THEORY OF VISCOSITY:
 It states that more viscous emulsion the greater is the stability. But it is not always true.
 This theory is holds good for emulsions prepared with gums as emulsifying agents
Example:
 Milk has low viscosity but most stable, O/W emulsion.
 Cold Cream is an example of more viscous emulsion, O/W emulsion

FISCHER’S THEORY OF HYDRATES AND SOLVATES:

 Fischer’s observed that the use of specific ratios of emulsifying agent to continuous phase, he
claimed that the quantity of water in these specified ratios was all used up in forming a
colloidal hydrate.
 It states that disperse phase form colloidal hydrate or colloidal complex.
Example:
 O/W emulsion, oil form colloidal complex and in W/O emulsion water form colloidal
complex and known as solvate.

Additives for Formulation of Emulsion:

1. ANTI-OXIDANTS:
Autoxidation occurs by free radical reaction
 Can be prevented by
 Absence of oxygen
 A free radical chain breaker
 By reducing agent
 Examples:
 Gallic acid, Propyl gallate - pharmaceuticals and cosmetics - Bitter taste
 Ascorbic acid – Suitable for oral use products
 Sulphites - Suitable for oral use products
 L-tocopherol - pharmaceuticals and cosmetics -Suitable for oral preparations
 e.g. those containing vitamin A
The oxidative decomposition of certain excipients, the oil phase, and some
pharmaceuticals is possible in emulsions, not only due to the usual amount of air
dissolved in the liquid and the possible incorporation of air during the preparation of the
product, but also the large interfacial area between the oil and water phase.
The selection of the appropriate antioxidant depends on such factors as:
 Stability
 Compatibility with the ingredients of the emulsion
 Toxicity
 Effectiveness in emulsions
 Odor
 Taste
 Distribution between the two phases
2. ANTI-MICROBIAL PRESERVATIVES:
The preservative must be:
 Less toxic
 Stable to heat and storage
 Chemically compatible
 Reasonable cost
 Acceptable taste, odor and color.
 Effective against fungus, yeast, bacteria.
 Available in oil and aqueous phase at effective level concentration.
 Preservative should be in unionized state to penetrate the bacterial membrane
 Preservative must no bind to other components of the emulsion, because the
complexes are ineffective as preservatives. Only the concentration of free, or
unbound, preservative is effective
Examples:
 Acids and acid derivatives – Benzoic acid, Antifungal agent
 Aldehydes – Formaldehyde - Broad spectrum
 Phenolics – Phenol (Broad spectrum)
 Benzalkonium chloride

VISCOSITY AGENTS:
Viscosity agents are added in emulsion.
Hydrophilic colloids (naturally occurring gums)
Partially synthetic polymers, such as cellulose derivatives (e.g., Methylcellulose, hydroxyl-propyl
methyl cellulose, sodium carboxy-methylcellulose)
Synthetic polymers (carbomer polymer).
These materials are hydrophilic in nature and dissolve or disperse in water to give viscous solutions
and function as emulsion stabilizers.
High molecular weight alcohols (stearyl alcohol, cetyl alcohol, and glyceryl monostearate) are
employed primarily as thickening agents and stabilizers for o/w emulsions of certain lotions and
ointments used externally.
Emulsifying Agents:
They are the substances added to an emulsion to prevent the coalescence of the globules of the
dispersed phase. They are also known as emulgents or emulsifiers.
They help in formation of emulsion by three mechanisms.
i. Reduction in interfacial tension – thermodynamic stabilization
ii. Formation of a rigid interfacial film – mechanical barrier to coalescence, it should possess
some degree of surface elasticity and should not thin out and rupture when sandwiched
between two droplets
iii. Formation of an electrical double layer – electrical barrier to approach of particles.

Ideal properties of emulsifiers:

 Be stable
 Be compatible with other ingredients
 Be non – toxic
 Possess little odor , taste , or color
 Not interfere with the stability and efficacy of the active agent
 Promote emulsification to maintain the stability of the emulsion for the intended shelf life of
the product

Desirable Properties:
 Some of the desirable properties of an emulsifying agent are that it should be surface active
and reduce surface tension to below 10 dynes/cm.
 Be adsorbed quickly around the dispersed drops as a condensed, non-adherent film that will
prevent coalescence.
 Impart to the droplets an adequate electrical potential so that mutual repulsion occurs.
 Increase the viscosity of the emulsion.
 Be effective in a reasonably low concentration

HLB System:
HLB (Hydrophilic lipophilic balance) is the balance of strength of hydrophilic or lipophilic portion
of surfactant molecule. Hydrophilic lipophilic balance (HLB) of a surfactant is a measure of the
degree to which it is hydrophilic or lipophilic, determined by calculating values for the different
regions of the molecule. Each emulsifying agent has a hydrophilic portion and a lipophilic portion,
with one or the other being more or less predominant and influencing the type of emulsion.
As the emulsifier becomes more hydrophilic, its solubility in water increases and the formation of an
O/W emulsion is favored. Conversely, W/O emulsions are favored with the more lipophilic
emulsifiers.
Griffin developed a scale based on the balance between these two opposing tendencies. This so-
called HLB scale is a numerical scale. The more hydrophilic surfactants have high HLB numbers (in
excess of 10), whereas surfactants with HLB numbers from 1 to 10 are considered to be lipophilic.
RELATIONSHIP BETWEEN HLB RANGE AND SURFACTANT
APPLICATION:
HLB Range Use
0-3 Antifoaming agent
4-6 W/O emulsifying agent
7-9 Wetting agent
8-18 O/W emulsifying agent
13-15 Detergents
10-18 Solubilizing agent
CLASSIFICATION OF EMULSIFIERS:
Emulsifying agents may be classified in accordance with the type of film they form at the interface
between the two phases. The main purpose of this film—which can be a monolayer, a multilayer, or
a collection of small particles adsorbed at the interface—is to form a barrier that prevents the
coalescence of droplets that come into contact with one another. The ionic nature of a surfactant is an
important consideration when selecting a surfactant for an emulsion. Nonionic surfactants are
effective over pH range 3–10; cationic surfactants are effective over pH range 3–7; and, anionic
surfactants require a pH of greater than 8.
SYNTHETIC EMULSIFYING AGENTS (MONOMOLECULAR FILMS):

The majority of emulsifiers forming monomolecular films are synthetic, organic materials.
May be subdivided into anionic, cationic, and nonionic, depending on the charge possessed by the
surfactant.
Anionics: In the anionic subgroup, the surfactant ion bears a negative charge.
Example: The potassium, sodium, and ammonium salts of lauric acid (Potassium laurate) and

oleic acid are soluble in water and are good O/W emulsifying agents.
Cationics: The surfactant ion bears a positively charged. These compounds have marked
bactericidal properties. This makes them desirable in emulsified anti-infective products such as
skin lotions and creams. The pH of an emulsion prepared with a cationic emulsifier lies in the pH
4 to 6 ranges.
Example: Quaternary ammonium compounds (Cetyltrimethyll ammonium bromide) Cationic
emulsifiers should not be used in the same formulation with anionic emulsifiers because they will
interact.
Non-ionics: Have no charge, find widespread use as emulsifying agents when they possess the
proper balance of hydrophilic and lipophilic groups within the molecule.
Example: Glyceryl esters, polyoxyethylene glycol esters and ethers, and the sorbitan fatty acid
esters and their polyoxyethylene derivatives.
NATURAL EMULSIFYING AGENT (MULTI-MOLECULAR FILMS):
Emulsifying agents derived from natural (i.e., Plant and animal) sources
Also known as Hydrocolloid Emulsifying agents
They differ, however, from the synthetic surface-active agents in that:
They do not cause an appreciable lowering of interfacial tension and They form a multi- rather
than a monomolecular film at the interface.Their action as emulsifying agents is due mainly to the
multi-molecular film because the films thus formed are strong and resist coalescence. These act
as a coating around the droplets and render them highly resistant to coalescence, even in the
absence of a well-developed surface potential. Furthermore, any hydrocolloid not adsorbed at the
interface increases the viscosity of the dispersion medium; this enhances emulsion stability.
Because the emulsifying agents that form multilayer films around the droplets are invariably
hydrophilic, they tend to promote the formation of o/w emulsions.
Examples:
Plant origin: Polysaccharides (Acacia, tragacanth, agar, pectin, lecithin)
Animal origin: Gelatin, Lecithin (Egg yolk), Cholesterol (Wool fat)

FINELY DISPERSED SOLIDS (SOLID PARTICLE FILMS):

Colloidal clays: Bentonite, (Al2O3.4SiO2.H2O)
Veegum (Magnesium Aluminium silicate) it is employed most extensively as stabilizer in
cosmetic lotions and creams. Metallic hydroxides: Magnesium hydroxides

AUXILIARY EMULSIFIERS:
Auxiliary (Secondary) emulsifying agents include those compounds that are normally incapable
themselves of forming stable emulsion. Their main value lies in their ability to function as
thickening agents and thereby help stabilize the emulsion. Cetyl alcohol, Stearyl alcohol.

Preparation of Emulsions:
For small scale work emulsions can be prepared by the following methods:
 Dry gum method
 Wet gum method
 Bottle method

1. DRY GUM METHOD:

This method is called as continental method
This method is also known as 4:2:1 method because these figures represent the proportions of oil,
water and gum acacia required for the preparation of primary emulsion.
That is, for example, if there are 40 ml of fixed oil to be emulsified then 10 example, if there are
40ml of fixed oil to be emulsified then 10 gm of gum acacia and 20 ml of water or vehicle will be
required for preparing the primary emulsion. Measure the given quantity of oil with a clean and dry
measure and transfer it to a dry mortar. To this add the calculated quantity of acacia and triturate
rapidly so as to form a uniform mixture. Then add the required quantity of water for primary
emulsion and triturate rapidly without ceasing till a clicking sound is produced and the product
becomes white or nearly white. At this stage the emulsion is known as primary emulsion. Then add
more of water to produce the required volume. If any soluble ingredient is also to be incorporated,
that must be dissolved in the second portion of water to be added after making the primary emulsion
and to produce the final volume.
2. WET GUM METHOD:
This method is also called English method.
The proportions of oil, water and gum are some as for dry gum method. In this method the calculated
quantity of gum is triturated with water to form mucilage. Then the given amount of oil is
incorporated in small portions with rapid titration until a clicking sound is produced and the product
becomes white or nearly so. When the primary emulsion is formed, the titration in continued for few
minutes more and then more of water is incorporated in successive small portions to produce the
required volume.

3. BOTTLE METHOD:
Bottle method is used for the preparation of emulsions of volatile and other non-viscous oils. The
emulsions can be prepared by both the dry gum and wet gum methods. Because of low viscosity the
volatile oils require greater amount of gum for emulsification therefore the proportions for oil, water
and gum for primary emulsion are 4:4: 2. In this method the oil is put in a large bottle and then the
powdered dry gum is added. The bottle is shaken vigorously until the oil and gum are mixed
thoroughly. Then the calculated amount of water is added all at once and the mixture is shaken
vigorously until primary emulsion is formed. More of water is added in small portions with constant
agitation after each addition, to produce the final volume.

Physical Stability of Emulsions:

A stable emulsion may be defined as a system in which the globules retain their initial character
and remain uniformly distributed throughout the continuous phase.
The stability of pharmaceutical emulsion is characterized by the:
Absence coalescence of the internal phase
Absence of creaming
Maintenance of elegance with respect to appearance, order colour and other physical properties
The instability of pharmaceutical emulsions may be classified follows:
 Flocculation and creaming
 Coalescence and breaking
 Some physical and chemical changes and
 Phase inversion
A. FLOCCULATION AND CREAMING:
Creaming is a phenomenon characterized by the accumulation of droplets of the dispersed phase on
the top of the emulsion.

B. COALESCENCE AND BREAKING OR CRACKING:

Cracking involves coalescence of the dispersed globules and provides eventual separation of the
emulsion in to two phases. Some of the factors that cause cracking are:
The addition of a substance that is incompatible with the emulsifier may destroy its emulsifier ability.
An increase in temperature may coagulate certain types of emulsifying agents (proteins)
Freezing of aqueous phase will produce ice crystals that may exert unusual pressure on the oil
globules.
Attempts to incorporate excessive amount of dispersed phase may cause cracking of an emulsion.
Those factors which reduce the chances of coalescence & breaking include:
Uniformity of particle size of the dispersed phase.
Increase in viscosity of the emulsion to optimum level since this hinders flocculation coalescence.
Phase volume ratio: the dispersed phase should be less than 74% otherwise the oil globules may
coalescence and emulsion may break.

C. PHYSICAL AND CHEMICAL CHANGES:

Natural gums, starches etc. used as emulsifiers may contain excessive amount of bacterial load.
Bacterial growth may cause change in PH and consequent breakdown of emulsion.
Synthetic emulsifiers are comparatively more stable.
Some emulsifiers such as soaps carry electric changes. Neutralization of the charge by on added
substance may cause breakdown of the emulsion.

D. PHASE INVERSION:
In phase inversion the o/w type emulsion changes into w/o type and vice versa.
It may be brought about by the addition of an electrolyte or by changing the phase volume ratio or by
temperature change.

Pharmaceutical Applications of Emulsions:

 Emulsions can be used to administer orally unpleasant tasting drugs such as liquid paraffin,
cod liver oil, and castor oil in a palatable formulation.
 Oil soluble as well as water soluble materials can be formulated in to a single dosage form
as an emulsion. For example, oil soluble vitamins, A, D, E, and water soluble ones like B &
C can be formulated as a palatable fine emulsion. Such formulation also leads to better
absorption of vitamins.
 Radio-opaque emulsions are used for diagnostic applications such as X-ray examination.
 O/w type emulsions are used for i/v administration of oil and fats with high caloritic value
patients who are to ingest food orally.