Outcomes of this lecture1- Definition and Classification of Emulsion

2- Pharmaceutical and medical application of Emulsion

3- Theories of Emulsification

4- Formulation of Emulsion

5- Emulsifying agants

6- Stability of suspensions & Quality control

An emulsion is liquid preparation containing two immiscible liquids, one of which is dispersed as globules

(dispersed phase = internal phase)

in the other liquid

(continuous phase = external phase).

Dispersed phase

Continuous phase

To stabilize these droplets, emulsifying agent should be added

Microemulsion: Droplets size range 0.01 to 0.1 m mMacroemulsion: Droplets size range approximately 5 m m.

General Types of Pharmaceutical Emulsions:

1) Lotions

2) Liniments

3) Creams

4) Ointments

5) Vitamin drops

Types of Emulsion

Oil-in-water emulsion Water-in-oil emulsion

Water

Oil

mm

Primary and secondary emulsion:

Primary emulsion containing one internal phase, for example, oil-in-water emulsion (o/w) and water-in-oil emulsion (w/o).

Secondary emulsion= multiple-emulsion: it contains two internal phase, for instance, o/w/o or w/o/w. It can be used to delay release or to increase the stability of the active compounds.

Multiple Emulsions

Water-in-oil-in-water emulsion Oil-in-water-in-oil emulsion

Water

Oil

mm

W/O/WO/W/O

O/W

OilWater

O/W

Oil

O/W

OilWater

Oil

W/O

WaterOil

W/OW/O

Water

Oil

WaterWater

Water

OilOil

Water

OilOil

Emulsion Size

< 0.5 mm 0.5-1.5 mm 1.5-3 mm >3 mm

A

Number Distributions

•<

0.5

mm

•0.

5-1.

5 m

m•

1.5-

3 m

m•

>3

mm

Num

ber Very few large

droplets contain most of the oil

Chemical Composition

Interfacial layer. Essential to stabilizing the emulsion

Oil Phase. Limited effects on the properties of the emulsion

Aqueous Phase. Aqueous chemical reactions affect the interface and hence emulsion stability

Emulsion Type and Means of Detection:

using of naked eye, it is very difficult to differentiate between o/w or w/o emulsions.

Thus, the four following methods have been used to identify the type if emulsions.

1) Dilution Test:

based on the solubility of external phase of emulsion.

- o/w emulsion can be diluted with water.

- w/o emulsion can be diluted with oil.

Few dropsof emulsion

Few dropsof water Water distribute

uniformly

Water separateout as layer

O/W emulsion

W/O emulsion

2) Conductivity Test:

water is good conductor of electricity whereas oil is non-conductor. Therefore, continuous phase of water runs electricity more than continuous phase of oil.

Electrode

Bulb

Emulsion = Bulb glows with O/W= Bulb doesn’t glow with W/O

3) Dye-Solubility Test:

- Water-soluble dye will dissolve in the aqueous phase.

- Oil-soluble dye will dissolve in the oil phase.

Oil-soluble dye (e.g. Scarlet) Water-soluble dye (e.g. Amaranth dye)

O/W W/OO/WW/O

What is look like under the microscope after mixing with suitable dye

4-Fluorescence test:

oils give fluorescence under UV light, while water doesn’t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces.

Pharmaceutical applications of emulsions:

1 ) To mask the taste

2) O/W is convenient means of orally administration of water-insoluble liquids

3) O/W emulsion facilitates the absorption of water-insoluble compounds comparing to their oily solution preparations (e.g. vitamins)

4) Oil-soluble drugs can be given parentrally in form of oil-in water emulsion. (e.g Taxol)

5) Emulsion can be used for external application in cosmetic and therapeutic uses.

Theories of Emulsification:

Incase of two immiscible liquids

OilOil

WaterWater

Oil

Water

Agitation

Separate rapidly into two clear defined layers

OilOil

WaterWater

Oil

Water

Agitation

Separate rapidly into two clear defined layers

An explanation of this phenomenon is because of cohesive force between the molecules of each separate liquid exceeds adhesive force between two liquids. This is manifested as interfacial energy or tension at boundary between the liquids.

System tends to separate intwo layer to reduce the surface area

Small droplet Surface area Interfacial tension

System is thermodynamically unstable “ high energy”

System tends to separate intwo layer to reduce the surface area

Small droplet Surface area Interfacial tension

System is thermodynamically unstable “ high energy”

Small droplet Surface area Interfacial tensionSmall droplet Surface area Interfacial tension

System is thermodynamically unstable “ high energy”

Therefore, to prevent the coalescence and separation, emulsifying agents have been used.

Types of emulsifying agents:

1) Surface active agent: adsorbed at oil/water interface to form monomolecular film to reduce the interfacial tension

2) Hydrophilic colloids: forming a multimolecular film around the dispersed droplet

3) Finely divided solid particles: they are adsorbed at the interface between two immiscible liquid phases to form particulate film

A- Monomolecular adsorption

W= . A

Surface areaInterfacial tensionSurface free

energy

In emulsion, the surface area is high to maintain the dispersion of the droplets. Thus, based on the above equation surface free energy becomes high consequently. The only way to keep it low is to reduce the interfacial tension.

Surface active agent (SAA) is molecule which have two parts, one is hydrophilic and the other is hydrophobic. Upon the addition of SAA, they tend to form monolayer film at the oil/water interface.

Hydrophilic head

Hydrophobic tail

Water

Oil

Form monomolecular film

The functions of surface active agents to provide stability to dispersed droplets are as following:

1) Reduction of the interfacial tension

2) Form coherent monolayer to prevent the coalescence of two droplet when they approach each other

3) Provide surface charge which cause repulsion between adjust particles

Combination of surface-active agents is used most frequently. The

combination should form film that closely packed and condensed

Classification of Emulsifying surfactants

1) Anionic group

2) Cationic group

3) Amphoteric group

4) Nonionic group

Classification of Emulsifying surfactants

Classification of surfactants

The "tail" of most surfactants are fairly similar, consisting of a hydrocarbon chain, which can be branch, linear, or aromatic.

Fluorosurfactants have fluorocarbon chains.

Siloxane surfactants have siloxane chains.

Classification of surfactants Most commonly, surfactants are classified according

to polar head group. A non-ionic surfactant has no charge groups in its

head. The head of an ionic surfactant carries a net charge.

If the charge is negative, the surfactant is more specifically called anionic; if the charge is positive, it is called cationic.

If a surfactant contains a head with two oppositely charged groups, it is termed zwitterionic.

Anionic

Sulfate, sulfonate, phosphate, and carboxylates. ammonium lauryl sulfate, sodium lauryl sulfate (SDS, sodium dodecyl sulfate, another name for the compound) and the related alkyl-ether sulfates sodium laureth sulfate, also known as sodium lauryl ether sulfate (SLES), and sodium myreth sulfate.

Docusates: dioctyl sodium sulfosuccinate, perfluorooctanesulfonate (PFOS), perfluorobutanesulfonate, linear alkylbenzene sulfonates (LABs).

Anionic

Carboxylates

These are the most common surfactants and comprise the alkyl carboxylates (soaps), such as sodium stearate. More specialized species include sodium lauroyl sarcosinate and carboxylate-based fluorosurfactants such as perfluorononanoate, perfluorooctanoate (PFOA or PFO).

Cationic head groups

pH-dependent primary, secondary, or tertiary amines:

Primary amines become positively charged at pH < 10, secondary amines become charged at pH < 4: Octenidine dihydrochloride;

Cationic head groups Permanently charged quaternary ammonium cation:

Alkyltrimethylammonium salts: cetyl trimethylammonium bromide (CTAB) a.k.a. hexadecyl trimethyl ammonium bromide, cetyl trimethylammonium chloride (CTAC

Cetylpyridinium chloride (CPC) Benzalkonium chloride (BAC) Benzethonium chloride (BZT) 5-Bromo-5-nitro-1,3-dioxane Dimethyldioctadecylammonium chloride Cetrimonium bromide Dioctadecyldimethylammonium bromide (DODAB)

Zwitterionic surfactants (amphoteric)

The cationic part is based on primary, secondary, or tertiary amines or quaternary ammonium cations.

The anionic part can be more variable and include sulfonates, as in CHAPS (3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate).

Other anionic groups are sultaines illustrated by cocamidopropyl hydroxysultaine. Betaines, e.g., cocamidopropyl betaine. Phosphates: lecithin

Nonionic surfactant Many long chain alcohols exhibit some surfactant

properties. Prominent among these are the fatty alcohols cetyl

alcohol, stearyl alcohol, and cetostearyl alcohol (consisting predominantly of cetyl and stearyl alcohols), and oleyl alcohol.

Nonionic surfactant Polyoxyethylene glycol alkyl ethers (Brij):

CH3–(CH2)10–16–(O-C2H4)1–25–OH:

- Octaethylene glycol monododecyl ether Pentaethylene glycol monododecyl ether

Polyoxypropylene glycol alkyl ethers:

CH3–(CH2)10–16–(O-C3H6)1–25–O

Nonionic surfactant

Glucoside alkyl ethers: CH3–(CH2)10–16–(O-Glucoside)1–3–OH:

- Decyl glucoside,

- Lauryl glucoside

- Octyl glucoside

Nonionic surfactant

Polyoxyethylene glycol octylphenol ethers:

C8H17–(C6H4)–(O-C2H4)1–25–OH: Triton X-100

Polyoxyethylene glycol alkylphenol ethers:

C9H19–(C6H4)–(O-C2H4)1–25–OH: Nonoxynol-9

Glycerol alkyl esters:

- Glyceryl laurate

Nonionic surfactant

Polyoxyethylene glycol sorbitan alkyl esters: Polysorbate

Sorbitan alkyl esters: Spans Cocamide MEA, cocamide DEA Dodecyldimethylamine oxide Block copolymers of polyethylene glycol and

polypropylene glycol: Poloxamers Polyethoxylated tallow amine (POEA).

B- Multimolecular adsorption

Hydrophilic colloids form multimolecular adsorption at the oil/ water interface. They have low effect on the surface tension.

Their main function as emulsion stabilizers is by making coherent multi-molecular film. This film is strong and resists the coalescence.

They have, also, an auxiliary effect by increasing the viscosity of dispersion medium.

Most of the hydrophilic colloids form oil-in-water emulsions.

Some of them can provide electrostatic repulsion like acacia, which contains Arabic acid and proteins (COOH and NH3)

colloids:

Polysaccharides Amphoterics Synthetic or semi-synthetic polymers

AcaciaAgarAlginic acidCarrageenanGuar gumKarraya gumTragacanth

Gelatin Carbomer resinsCellulose ethersCarboxymethyl chitinPEG-n (ethylene oxide polymer)

collo

ids

C- Solid particle adsorption

Finely divided solid particles are adsorbed at the surface of emulsion droplet to stabilize them.

Those particles are wetted by both oil and water (but not dissolved) and the concentration of these particles form a particulate film that prevent the coalescence.

Particles that are wetted preferentially by water form o/w emulsion, whereas those wetted more by oil form w/o emulsion

Note that they are very rare to use and can affect rheology of the final product

Size of the particle is very important, larger particles can lead to coalescence

Finely divided solids:

Finely divided solids

Bentonite

HectoriteKaolin

Magnesium aluminum silicateMontmorillonite

Aluminum hydroxideMagesium hydroxide

Silica

Other emulsifying agents

Egg yolk: it contains phospholipids and cholesterol. The main withdraw back is that spoils quickly; therefore, it can’t be used in industry.

Wool fat: anhydrous lanolin, it is used to prepare w/o emulsion for external uses.

Starch: it forms starch mucilage and it is restricted

for enemas preparation.

Cholesterol: it has stabilizing action; therefore, another emulsifier should be included.

CRITERIA FOR THE SELECTION OF EMULSIFYING AGENTS

An ideal emulsifying agent should posses the following characteristics:

It should be able to reduce the interfacial tension between the two immiscible liquids.

It should be physically and chemically stable, inert and compatible with the other ingredients of the formulation.

It should be completely non irritant and non toxic in the concentrations used.

It should be organoleptically inert i.e. should not impart any colour, odour or taste to the preparation.

It should be able to form a coherent film around the globules of the dispersed phase and should prevent the coalescence of the droplets of the dispersed phase.

It should be able to produce and maintain the required viscosity of the preparation.

Selection of Emulsifying Agents using HLB method

A system was developed by William C. Griffin to assist making systemic decisions about the amounts and types of surfactants needed in stable products. The system is called the HLB (hydrophile-lipophile balance) system.

HLB RANGE USE 0-3 Antifoaming agents 4-6 W/O emulsifying agent 7-9 Wetting agents 8-18 O/W emulsifying agent 13-15 Detergents 10-18 Solubilizing agents

Emulsifier with low HLB

An emulsifier having a low HLB number indicates that the number of hydrophilic groups present in the molecule is less and it has a lipophillic character.

For example, spans generally have low HLB number and they are also oil soluble. Because of their oil soluble character, spans cause the oil phase to predominate and form a w/o emulsion.

Emulsifier with high HLB

A higher HLB number indicate that the emulsifier has a large number of hydrophilic groups on the molecule and therefore is more hydrophilic in character.

Tweens have higher HLB numbers and they are also water soluble. Because of their water soluble character, tweens will cause the water phase to predominate and form an o/w emulsion.

DISADVANTAGE OF THE HLB SYSTEM

It does not take into account:

- the effect of temperature

- the presence of additives

- the concentration of emulsifier

HLB values of some common emulsifying agents

Emulsifying Agent  HLB ValueAcacia: 8Polysorbate 20 (Tween 20): 16.7Polysorbate 60: (Tween 60): 14.9Polysorbate 80 (Tween 80): 15Oleic acid: 4.3Sorbitan monolaurate (Span 20): 8.6Sorbitan monolaurate (Span 60): 4.7Sorbitan monolaurate (Span 80): 4.3

How to control emulsion type during formulation?

Volume of internal and external phases controls the type of emulsion.

The smaller volume will be for the internal phase and the larger volume will be for external phase. In some cases, internal phases can be more than 50% of the total volume.

Dominance of polar and non-polar characteristic of emulsifying agents (relative solubility of emulsifying agent in water and oil).

Dominance of polar part results in formation of o/w emulsion and dominance of non-polar part results in formation of w/o emulsion. Note that polar groups are better barriers than non-polar; therefore, o/w emulsion can be prepared with more than 50 % of oil phase “ internal phase”.

What the factors that affect the choice of emulsion type?

The choice of emulsion depends on: (1)-properties and uses of final products (2)- the other material required to be present.

Oil-soluble drug is prepared in o/w emulsion due its solubility and its taste can be masked by adding flavoring agents

For intravenous injection “ i.v.” o/w emulsion is the only type could be used.

For intramuscular injection “i.m.” both o/w and w/o types of emulsion could be used. Water-soluble drug can be prepared in w/o emulsion to get prolonged action (depot therapy)

Topical application: Semisolid emulsions are called creams and lotions

DIFFERENCE BETWEEN O/W AND W/O EMULSIONS

Oil in water emulsion

Water is the dispersion medium and oil is the dispersed phase For insoluble drug For local effect Easily to wash from skin Doesn’t have greasy texture of oily preparation Acceptable by consumer They are used externally to provide cooling effect e.g.

vanishing cream Water soluble drugs are more quickly released from o/w

emulsions They are preferred for formulations meant for internal use as

bitter taste of oils can be masked.

DIFFERENCE BETWEEN O/W AND W/O EMULSIONS (Contin…)

Water in oil emulsion

Oil is the dispersion medium and water is the dispersed phase For water soluble drug Can be use to hydrate the upper layer of stratum corneum

(moisturizing cream) Can increase the absorption of drug from these formulation Can be used to clean skin from dirt Oil soluble drugs are more quickly released from w/o emulsions They are preferred for formulations meant for external use like

creams. Not acceptable by consumer

Properties of emulsionThe basic properties which should be present in

an emulsion include: appearance, feel, odour, desirable viscosity, consistency, effectiveness, stability.

These properties depends on the: ingredients, type of emulsion, ratio of the two phases, type and quantity of emulsifying agents, method of emulsification .

O/w emulsions will generally have a sheen or matte surface as compared to w/o emulsions which have a shiny or oily surface due to the presence of oil as external phase.

W/o emulsios are oily and greasy in nature, not easily removable from the surface of the skin whereas o/w emulsions are non greasy and easily removable from the skin surface.

The viscosity of the emulsions depends generally on the viscosity of the continuous phase. As the ratio of dispersed phase increases, the viscosity also increases to a point where emulsion starts loosing its fluidity

Methods for preparing Emulsions for Internal use

1- Trituration MethodThis method consists of dry gum method and wet gum method.

Dry Gum MethodIn this method the oil is first triturated with gum with a little amount of

water to form the primary emulsion. The trituration is continued till a characteristic ‘clicking’ sound is heard and a thick white cream is formed. Once the primary emulsion is formed, the remaining quantity of water is slowly added to form the final emulsion.

Wet Gum MethodAs the name implies, in this method first gum and water are triturated

together to form a mucilage. The required quantity of oil is then added gradually in small proportions with thorough trituration to form the primary emulsion. Once the primary emulsion has been formed remaining quantity of water is added to make the final emulsion.

2- Bottle Method This method is employed for preparing emulsions

containing volatile and other non-viscous oils. Both dry gum and wet gum methods can be employed for

the preparation. As volatile oils have a low viscosity as compared to fixed

oils, they require comparatively large quantity of gum for emulsification.

In this method, oil or water is first shaken thoroughly and vigorously with the calculated amount of gum. Once this has emulsified completely, the second liquid (either oil or water) is then added all at once and the bottle is again shaken vigorously to form the primary emulsion. More of water is added in small portions with constant agitation after each addition to produce the final volume.

Methods of Preparation of Emulsions:

1) Continental or Dry Gum Method:

"4:2:1" Method

4 parts (volumes) of oil 2 parts of water1 part of gum

Acacia or other o/w emulsifier is triturated with oil in a perfectly dry Wedgwood or porcelain mortar until thoroughly mixed.

Glass mortar has too smooth a surface to produce the proper size reduction of the internal phase (Do not use glass mortar).

After the oil and gum have been mixed, the two parts of water are

then added all at once and the mixture is triturated immediately.

2) English or wet Gum Method:

Mucilage of the gum is prepared by triturating acacia (or other emulsifier) with water.

The oil is then added slowly in portions, and the mixture is triturated to emulsify the oil.

Should the mixture become too thick during the process, additional water may be blended into the mixture before another successive portion of oil is added.

3) Bottle or Forbes Bottle Method:

Useful for extemporaneous preparation of emulsion from volatile oils or oleaginous substance of low viscosity.

1- Put powdered acacia in a dry bottle.

2- Add 2 parts of oil

3- Thoroughly shake the mixture in the capped bottle.

4- A volume of water approximately equal to the oil is then added in portions, the mixture being thoroughly shaken after each addition.

This method is not suitable for high viscous oils

Points to be considered during formulations of emulsions

Stability of the active ingredient Stability of the excipients Visual appearance Color Odor (development of pungent odor/loss of

fragrance) Viscosity, extrudability Loss of water and other volatile vehicle

components

Points to be considered… (Continued)

Concentration of emulsifier Order of addition of ingredients Particle size distribution of dispersed phases pH Temperature of emulsification Type of equipment Method and rate of cooling

Points to be considered… (Continued)

Texture, feel upon application (stiffness, grittiness, greasiness, tackiness, spreadibility)

Microbial contamination/sterility (in the unopened container and under conditions of use)

Release/bioavailability (percutaneous absorption)

Phase distribution, Phase Inversion (homogeneity/phase separation)

Quality control tests for Emulsions

1. Determination of particle size and particle count:

It is performed by optical microscopy, sedimentation by using Andreasen apparatus and Coulter counter apparatus.

2. Determination of phase separation:

Phase separation may be observed visually or by measuring the volume of the separated phases.

Quality control tests….(Contin..)3. Determination of viscosity: The viscometers which should be used include cone and plate

viscometers. Capillary and falling sphere type of viscometrs should be avoided.

For viscous emulsions, the use of penetrometer is recommended

as it helps in the determination of viscosity with age.

In case of o/w emulsions, flocculation of globules causes an immediate increase in viscosity. After this change, the consistency of the emulsion changes with time.

In case of w/o emulsions, the dispersed phase particles flocculate quite rapidly resulting in a decrease in viscosity, which stabilizes after 5 to 15 days.

As a rule, a decrease in viscosity with age reflects an increase of particle size due to coalescence.

Quality control tests….(Contin..)

4. Determination of electrophoretic properties:

Determination of electrophoretic properties like zeta potential is useful for assessing flocculation since electrical charges on particles influence the rate of flocculation.

O/W emulsion having a fine particle size will

exhibit low resistance but if the particle size increase, then it indicates a sign of oil droplet aggregation and instability.

Instabilities In Emulsions An emulsion is a thermodynamically unstable

preparation so care has to be taken that the chemical as well as the physical stability of the preparation remains intact throughout the shelf life.

There should be no appreciable change in the mean particle size or the size distribution of the droplets of the dispersed phase and secondly droplets of the dispersed phase should remain uniformly distributed throughout the system.

Emulsion Destabilization

Creaming Flocculation Coalescence Combined methods

Instabilities In Emulsions…(Con..)

1- Creaming

An emulsion is said to cream when the oil or fat rises to the surface, but remains in the form of globules, which may be redistributed throughout the dispersion medium by shaking.

An oil of low viscosity tends to cream more readily than one of high viscosity.

Increasing the viscosity of the medium decreases the tendency to cream.

Creaming is a reversible phenomenon which can be corrected by mild shaking.

Creaming

Buoyancy(Archimedes)

Friction(Stokes-Einstein)

cs

gdv

18

2

h Continuous phase viscosityDr density differenceg Acceleration due to gravityddroplet diameterv droplet terminal velocityvs Stokes velocity

Instabilities In Emulsions…(Con..)

The factors affecting creaming are best described by strokeâs law:

V= 2r2 (d1-d2) g/9η

Where; V= rate of creaming

r=radius of globules

d1= density of dispersed phase

d2= density of dispersion medium

g= gravitational constant

η = viscosity of the dispersion medium

The following approaches can be used for decreasing Creaming

Reduction of globule size: According to strokeâs law, rate of creaming is

directly proportional to the size of globules. Bigger is the size of the globules, more will be the creaming. Therefore in order to minimize creaming, globule size should be reduced by homogenization.

Increasing the viscosity of the continuous phase: Rate of creaming is inversely proportional to the

viscosity of the continuous phase i.e. more the viscosity of the continuous phase, less will the problem of creaming. The viscosity of the continuous phase should be increased by adding suitable viscosity enhancers like gum acacia, tragacanth etc.

Instabilities In Emulsions…(Con..)

2- CrackingOccasionally, it happens that an emulsion cracks during

preparation, i.e., the primary emulsion does not become white but acquires an oily translucent appearance. In such a case, it is impossible to dilute the emulsion nucleus with water and the oil separates out.

Cracking of emulsion can be due to: addition of an incompatible emulsifying agent, chemical or microbial decomposition of

emulsifying agent, addition of electrolytes, exposure to increased or reduced temperature, change in pH.

Instabilities In Emulsions…(Con..)

3- Phase Inversion In phase inversion o/w type emulsion changes into

w/o type and vice versa. It is a physical instability. It may be brought about by the addition of an

electrolyte or by changing the phase volume ratio or by temperature changes.

Phase inversion can be minimized by: using the proper emulsifying agent in

adequate concentration, keeping the concentration of dispersed phase

between 30 to 60 % storing the emulsion in a cool place.

Instabilities In Emulsions…(Con..)

4- Breaking:

Separation of the internal phase from the external phase is called BREAKING of the emulsion.

All or part of the liquid of the internal phase becomes "unemulsified on the top or bottom of the emulsion.

This is irreversible

Instabilities In Emulsions…(Con..)

5- Aggregation:

The internal phase tends to form aggregates of globules.

Large globules or aggregates of globules rise to the top or fall to the bottom of the emulsion to form a concentrated layer of the internal phase.

Flocculation and Coalescence

Film ru

pture

Rehom

ogenization

Collision and sticking (reaction)

Stir or change chemical conditions FLOCCULATION

COALESCENCE

Rheology of Flocculated Emulsions

Flocculation leads to an increase in viscosity

Water is trapped within the floc and must flow with the floc

Effective volume fraction increased

rg

Gelled Emulsions

Thin liquid Viscous liquid Gelled solid

Creaming & Slight Flocculation

• Flocs have larger effective size

• Smaller Dr• Tend to cream much

faster

Creaming & Extreme Flocculation

• Heavily flocculated emulsions form a network

• Solid-like properties (gel)

• Do not cream (may collapse after lag period)

Preservation Of Emulsions1- Preservation from microorganisms:

It is necessary to preserve the emulsions from microorganisms as these can proliferate easily in emulsified systems with high water content, particularly if carbohydrates, proteins or steroidal materials are also present.

Contamination due to microorganisms can result in problems such as:

color and odor change, gas production, hydrolysis, pH change, and eventually breaking of emulsion

An ideal preservative should be nonirritant, nonsensitizing and nontoxic in the

concentration used.

It should be physically as well as chemically compatible with other ingredients of the emulsions and with the proposed container of the product.

It should not impart any taste, color or odor to the product.

It should be stable and effective over a wide range of pH and temperature.

It should have have a wide spectrum of activity against a range of bacteria, yeasts and moulds.

The selective preservative should have high water solubility and a low oil/water partition coefficient.

It should have bactericidal rather than bacteriostatic activity.

Examples of antimicrobial preservatives used to preserve emulsified systems:

parahydroxybenzoate esters such as methyl, propyl and butyl parabens,

organic acids such as ascorbic acid and benzoic acid, organic mercurials such as phenylmercuric acetate

phenylmercuric nitrate, quarternary ammonium compounds such as

cetrimide, cresol derivatives such as chlorocresol miscellaneous agents such as sodium benzoate,

chloroform and phenoxyethanol.

Preservation Of Emulsions… (Con.)

2- Preservation from oxidation:

Oxidative changes such as rancidity and spoilage due to atmospheric oxygen and effects of enzymes produced by micro-organisms is seen in many emulsions containing vegetables and mineral oils and animal fats.

Antioxidants are agents having a high affinity for oxygen and compete for it with labile substances in the formulation.

The ideal antioxidant should be nontoxic, nonirritant, effective at low concentration under the expected

conditions of storage and use, soluble in the medium and stable. Antioxidants for use in oral preparation should also

be odorless and tasteless.

Some of the commonly used antioxidants for emulsified systems include:

alkyl gallate such as ethyl, propyl or dodecyl gallate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT)

Stability testingStability testing of emulsions involves

determining stability at long term storage conditions, accelerated storage conditions, freezing and thawing conditions. Stress conditions are applied in order to speed up the stability testing.

The stress conditions used for speeding up instability of emulsions include:

Centrifugal force Agitational force Aging Temperature

The following physical parameters are evaluated to assess the effect of any of the above stress conditions:

Phase separation Viscosity Electrophoretic properties Particle size and particle count

Packaging, Labelling And Storage Of Emulsions

Depending on the use, emulsions should be packed in suitable containers.

Emulsions meant for oral use are usually packed in well filled bottles having an air tight closure.

Light sensitive products are packed in amber coloured bottles.

For viscous emulsions, wide mouth bottles should be used.

Packaging, Labelling And Storage Of Emulsions

The label on the emulsion should mention that these products have to be shaken thoroughly before use.

External use products should clearly mention on their label that they are meant for external use only.

Emulsions should be stored in a cool place but refrigeration should be avoided as this low temperature can adversely effect the stability of preparation

Routes of administration of emulsions

Oral Emulsions:

Generally o/w emulsions are used for internal use as the oil is more readily absorbed in a fine state of subdivision through the gastro intestinal tract and secondly the preparation becomes more palatable when water forms the continuous phase, as the medicinal oil is enveloped in a thin film of emulgent which masks the bitter and oily taste of the drug like liquid paraffin.

Orally emulsions are also used to facilitate the absorption of the oil soluble drugs like vitamins A,D, E and K.

Liquid Paraffin Oral Emulsion

Liquid Paraffin 500 ml Methyl cellulose 20 g Vanillin 0.5 g Chloroform 2.5 ml Benzoic acid solution 20 ml Saccharin sodium 0.05 g Purified Water q.s 1000ml

Uses: Laxative. It acts as an emollient purgative in chronic constipation especially during pregnancy and old age.

Castor oil Emulsion

Castor oil 16 ml Gum acacia q.s Water 80 ml

Uses: Purgative

Cod-Liver oil Emulsion

Cod-liver oil 30 ml Syrup 12 ml Ferric ammonium citrate 4 g Cinnamon water q.s. 90 ml

Uses: Source of vitamin A and D.

Topical Emulsions:

For external use, emulsions may be either o/w or w/o type.

Emulsions finds the maximum use in topical preparations , both for therapeutic and cosmetic use.

Therapeutically they are used as carrier for a drug.

In cosmetic industry o/w emulsions have been used for formulation of moisturing lotions, hand lotions and make up foundation lotions.

When oily layers are desired to prevent moisture loss from the surface of skin, for barrier action and for cleansing action, then w/o emulsions are formulated like cold creams.

Antiseptic cream

Cetrimide 1g Cetostearyl alcohol 10 g White soft paraffin 10 g Liquid paraffin 29 g Purified water 50 g

Uses: Antiseptic cream for the treatment of cuts, wounds and burns.

Cold Cream

Liquid paraffin 20 g Hard paraffin 4.5 g Lanette wax 3.5 g Glycerine 4.5 g Water 17.5 g Propyl paraben 0.1 g

Uses: Skin protective and skin smoothner.

Briefing

Types Of Emulsions

Oil in water emulsions Water in oil emulsions Multiple emulsions Microemulsions

Oil in water Emulsions (O/W): In this emulsion oil is the dispersed phase and

water is the dispersion medium.

The common example is milk.

These emulsions are used mainly for internal/oral use as bitter or disagreeable taste and odor of drugs can be masked by emulsification.

Externally these emulsions are used for formulating non greasy creams, lotions and liniments.

Cosmetic products prepared using o/w emulsions can easily be removed from the surface of the skin

Example: Castor oil emulsion, foundation creams, vanishing creams.

Oil in water Emulsions (O/W):

Water in oil Emulsions (W/O):

In this emulsion water is the dispersed phase or the internal phase and oil is the dispersion medium or the external phase.

They are mainly used externally as lotions and creams as the external layer of oil forms an occlusive layer and prevents the evaporation of moisture from the surface of the skin.

They are also effective as cleansing cream as they solubilize the oil soluble dirt from the surface.

Example: Cold creams.

Water in oil Emulsions (W/O):

Multiple Emulsions :

In this emulsion, oil in water (o/w) or water in oil emulsion (w/o)s is dispersed in another liquid medium to produce oil in water in oil (o/w/o) emulsion or water in oil in water (w/o/w) emulsion.

Multiple emulsions are primarily used for formulating sustained release dosage forms as the drug entrapped in the innermost layer has to pass through the other two phases before being released for absorption.

Water in oil in water (W/O/W) multiple emulsion

Oil in water in oil (O/W/O) multiple emulsion

Microemulsions: Microemulsions are thermodynamically stable

clear isotropic solution of oil, water and amphiphile (Emulsifying agent).

They are homogeneous in nature.

They contain globules having a diameter ranging from 0.1 to 100 micrometers.

These emulsions appear as transparent solutions and are more acceptable physically as compared to conventional emulsions.

Advantages of Emulsions

1. They can mask the bitter taste and odor of drugs, thereby making them more palatable. e.g. castor oil, cod-liver oil etc.

2. They can be used to prolong the release of the drug thereby providing sustained release action.

3. Essential nutrients like carbohydrates, fats and vitamins can all be emulsified and can be administered to bed ridden patients as sterile intravenous emulsions.

Advantages of Emulsions

4. Emulsions provide protection to drugs which are susceptible to oxidation or hydrolysis.

5. Intravenous emulsions of contrast media have been developed to assist in diagnosis.

6. Emulsions are used widely to formulate externally used products like lotions, creams, liniments etc.

Clinical Uses of Emulsions

1. Oral (Liquid administration of oils, eg. Vitamins A, D, and E) Reasons of use:

No oily mouth-feel (if an o/w emulsion is used).

Better taste than if completely solubilized. May be more bioavailable. Solubilized drug may be more bioavailable

Clinical Uses of Emulsions

2. Parenteral Drug Solubilization:

Emulsification of oils. Emulsification of lipids for parenteral nutrition.

Clinical Uses of Emulsions

3. Topical

O/W emulsions: Drug suspended or solubilized in the oil phase; less greasy than petrolatum type bases; no occlusion.

W/O emulsions: some occlusive effect but slightly less greasy than the petrolatum bases.

Tests Used To Identify Emulsion Type

Dilution test

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Conductivity Test

Dye Solubility Test

Fluorescence Test

If an emulsion on exposure to ultra-violet radiations shows continuous florescence under microscope, then it is w/o type and if it shows only spotty fluorescence, then it is Oil in o/w type

Cobalt Chloride Test

When a filter paper soaked in cobalt chloride solution is added to an emulsion and dried, it turns from blue to pink, indicating that the emulsion is o/w type.

Types of emulsifying agents:

1) Surface active agent:

forming a monomolecular film

2) Hydrophilic colloids:

forming a multimolecular film

3) Finely divided solid particles: forming a particulate film

Surface active agent:

Hydrophilic colloids:

Finely divided solid particles:

Emulsions Preparation Methods

1- Trituration Method Dry Gum Method Wet Gum Method

2- Bottle Method

Emulsions Quality control tests

1. Determination of particle size and particle count:

2. Determination of phase separation

3. Determination of viscosity

4. Determination of electrophoretic properties

Hope you be a good Emulsion Maker