By: Saleem Mansoor

Definition

Particle Size

Composition

Emulsifying Agent

Emulsification Equipment

Types Of Emulsion

Stability of Emulsions

Preparation of Emulsion

DefinitionAn emulsion may be defined as thermodynamically

unstable biphasic system consisting of two immiscibleliquids, one of which (the dispersed phase) is finely anduniformly dispersed as globules throughout the secondphase (the continuous phase) stabilized with emulsifyingagent.

Particle SizeThe particle size of the dispersed phase commonly ranges from 0.1 to 100 μm.

Composition

Internal/Discontinuous/Dispersed phase External/Continuous phase Emulsifying agent

Emulsifying Agent

Emulsifier or surface active agent (SAA) is molecule which has two parts, one is hydrophilic and the other is hydrophobic. It should be:

stable chemically non toxic non irritant suitably low in colour, odour and taste inexpensive

Mechanism of emulsifying agent:

Mechanism of action of emulsifying agents depends upon theformation of film they form at the interface of two phases.There are three types of films formed by emulsifying agents

Monomolecular films:

Emulsifying agents with stabilizing action formmonolayer at the oil-water interface. This monolayerprevents coalescence of droplets.The functions of surface active agents to provide stabilityto dispersed droplets are as following:

Reduction of the interfacial tension. Form coherent monolayer to prevent the coalescence of

two droplets when they approach each other. Provide surface charge which cause repulsion between

adjust particles.

Multi molecular films:

Multi molecular films around the droplets of dispersed phase are formed by hydrophilic colloids. They act as coats around the droplets making them highly resistant to coalescence. They have the ability of swelling

Hydrophilic colloids form multi molecular 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.

Solid particle films:

Small solid particles like bentonite, veegum, magnesiumhydroxide, aluminum hydroxide and magnesiumtrisilicate, that are wetted to some degree by both oil andwater can act as emulsifying agents. This results fromtheir being concentrated at the interface, where theyproduce a particulate film around the dispersed dropletsto avoid coalescence

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

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

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

Emulsification equipments:Various types of equipments are available for

emulsification on laboratory scale and commercial scale. Usually equipment for emulsification is selected on the basis of resulting emulsion.

Small scale processing: For the laboratory scale or

prescription department emulsification of fixed/volatile oils, the most frequently used equipments are Wedgwood or porcelain mortars and pestles.

Shaker mixers/agitators:In shaker mixers for small scale production, the material in the container is agitated by oscillator, whereas for large scale production, the material in the container is agitated by rotary movement similar to that of ball mills

Propeller mixers:Large and small scale production of emulsion is often made conveniently with the help of propellant mixers operating in suitable mixing container. Propellant mixers are generally used for low viscosity emulsion preparation and they can be rotated at a speed of about 8000 RPM.

Turbine mixers:Turbine mixers are used for mixing the high viscosity emulsions. They are rotated at a slow rate as compared to the propellant mixers. They are provided generally in a circular disc impeller attachment to short straight or curved blades.

Homogenizers:High pressure homogenizers are provided with a high pressure pump and homogenizing nozzle. The high pressure pump raises the pressure up to 50 to 500. During emulsification, the dispersion of two liquids is carried out by forcing them through a small orifice at a high pressure .The rotor/stator assembly of the homogenizer consists of a rotor with blades and a stator with openings. As the rotor rotates, a vacuum is created drawing the liquid in and out of the assembly, resulting in liquid circulation. The size of the dispersed phase is reduced;

1. Due to the mechanical collision against the walls of Homogenizer because of high liquid acceleration and

2. Due to the sheer force occurring within the gap between rotor and stator

Ultrasonifiers:Their mechanism of work is that the dispersion is forcedthrough an orifice at a medium pressure of 150 to 350 psiand is allowed to collide upon a blade.Ultrasonifiers provide an easy way of agitation for thelaboratory scale preparation of constant and reproducibleoil-in-water (o/w) emulsions

Colloid mills:Colloid mills are suitable for the preparation of emulsionson a continuous basis. Due to intense shearing force, theemulsions produced by colloid mills are of very smallglobule size Colloid mills are mostly used for the milling ofsolids and for the dispersion of very poorly wetablesuspensions; however, colloid mills are very useful for thepreparation of relatively high viscous emulsions

Whisks/churns:These are used for emulsion preparation involving the agitation of emulsion ingredients by blenders fitted in the container. Sometime, the containers may be fitted with a jacket if heating/cooling effects are required.

Micro-fluidizers:For the production of very fine particles, micro-fluidizers

are employed. Micro-fluidizers consist of interaction chambers with micro-channels. During emulsion processing, the emulsion is subjected to a high velocity through the micro-channels of the interaction chamber; thus, the particles are subjected to high shear, uproar, collision and cavitations.

General Types of Pharmaceutical Emulsions:

1) Lotions 2) Liniments3) Creams 4) Ointments 5) Vitamin drops

Emulsions are Divided into:

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.

Emulsion Type and Means of Detection:By use of naked eye, it is very difficult to differentiate

between o/w or w/o emulsions. Thus, the four followingmethods have been used to identify the type of emulsions.

1) Dilution Test:based on the solubility of external phase of emulsion.

- o/w emulsion can be diluted with water.- w/o emulsion cannot be diluted with oil.

Few drops

of emulsion

Few drops

of water Water distribute

uniformly

Water separate

out as layer

O/W emulsion

W/O emulsion

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

Dye-Solubility Test: Water-soluble dye will dissolve in the aqueous phase.

Oil-soluble dye will dissolve in the oil phase.

Fluorescence test: Oils give fluorescence under UV light, while water doesn’t.

Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces.

Stability of emulsions

A very important parameter for emulsion products is their stability; The instability of emulsion may be classified into four phenomenon:

Flocculation creaming coalescence and breaking Phase inversion

Flocculation:

It is the association of small emulsion particles to form large aggregatewhich is redispersable upon shaking. It is a reversible process in which thedroplets remain intact. Flocculation is considered as the precursor ofcoalescence. This is because the presence of excess surfactant in thecontinuous phase of an emulsion can lead to flocculation of emulsiondroplets. The flocculation of emulsion droplets by excess surfactant occursbecause of the so called "depletion effect". The depletion mechanism canbe explained as, a system containing excess surfactant in the form ofmicelles, when the dispersed emulsion droplets approach each other todistances closer than the diameter of the surfactant micelles, segregationof micelles from the inter-particle space that occurs because of the loss inconfigurational entropy of the micelles. This phenomenon results in anattractive force between the droplets due to the lowering of osmoticpressure in the region between the droplets, and accordingly, flocculationof droplets occur.

Creaming:Creaming is the phenomenon in which the dispersed phase

separates out, forming a layer on the top of the continuous phase. It is notable that in creaming, the dispersed phase remains in globules state so that it can be re-dispersed on shaking. Creaming can be minimized if the viscosity of the continuous phase is increased.

O/W emulsions generally face upward creaming when the globules of the dispersed phase are less dense than the continuous phase. In contrast, W/O emulsions face downward creaming when the globules of the dispersed phase are denser than the continuous phase.

Coalescence (synonyms: breaking or cracking):A more subtle type of emulsion instability, coalescence occurs when the

mechanical or electrical barrier is insufficient to prevent the formation of progressively larger droplets. Stabilization against coalescence may be achieved by the addition of high boiling point or high molecular weight components to the continuous phase. Newman (1914) and Schulman and Cockbain (1940) experimentally concluded that W/O emulsions are formed only when the film of emulsifying agent in the interface is uncharged and rigid as a result of complex formation. They were of the view that a W/O emulsion cannot be stabilized against flocculation by charge on the dispersed phase of water droplets, because an electric diffuse layer cannot be built up as oil being a nonionizing medium. A surface potential considerably higher than 25 mv is not sufficient to stabilize the droplets of dispersed phase with a radius ≥1 μ against flocculation. This is because of the high sedimentation velocities Stability of W/O emulsions against coalescenceAccording to Newman (1914) and Schulman and Cockbain (1940) a charged film is not able to prevent coalescence, because due to the repulsion between emulsifying molecules in the interface, no interlinked solid thick film can be formed

Phase inversion:In this w/o is converted to o/w and vice versa.

METHODS OF PREPARATION OF EMULSIONS

Emulsification processMilk is a natural emulsion, which consists of fatty globules surrounded by a layer of casein, suspended in water. The theory of emulsification is based on the study of milk. When a pharmaceutical emulsion is to be prepared the principal consideration is the same as that of milk

General methodGenerally, an O/W emulsion is prepared by dividing the oily phase completely into minute globules surrounding each globule with an envelope of emulsifying agent and finally suspends the globules in the aqueous phase. Conversely, the W/O emulsion is prepared by dividing aqueous phase completely into minute globules surrounding each globule with an envelope of emulsifying agent and finally suspending the globules in the oily phase

1) Continental and dry gum methodExtemporaneously emulsions are usually made by

continental or dry gum method. In this method, the emulsion is prepared by mixing the emulsifying agent (usually acacia) with the oil which is then mixed with the aqueous phase. Continental and dry gum methods differ in the proportion of constituents:

4 : 2 : 1 oil : water: gum

Primary Emulsifier is triturated with the oil in perfectly dry porcelain mortar2 parts of water are added at once triturate immediately, rapidly and continuously (until get a cracking sound).

2) Wet gum methodIn this method, the proportion of the constituents is same as those used in the dry gum method; the only difference is the method of preparation. Here, the mucilage of the emulsifying agent (usually acacia) is formed. The oil is then added to the mucilage drop by drop with continuous trituration.

3) Bottle or Forbes Bottle Method Extemporaneous preparation for volatile oils or oil with low viscosity gum + 2 parts of oil (dry bottle) shake water (volume equal to oil)is added in portions and shake.

4) Beaker MethodOil phase: heated about 5-10 degree above the highest melting point of ingredient (water bath) Water phase: heated to the same temperature of Oil phase (water bath) Add internal phase into external phase, mix, constant agitation being provided throughout the time of additionCaution: - not to heat the phase above 85 degree- rate of cooling determining the final texture and consistency.

5) Phase inversion methodIn this method, the aqueous phase is first added to the oilphase so as to form a W/O emulsion. At the inversion point,the addition of more water results in the inversion ofemulsion which gives rise to an O/W emulsion.

6) Membrane emulsification methodIt is a method, which is based on a novel concept ofgenerating droplets “drop by drop” to produce emulsion.Here, a pressure is applied direct to the dispersed phasewhich seeps through a porous membrane into the continuousphase and in this way the droplets formed are then detachedfrom the membrane surface due to the relative shear motionbetween the continuous phase and membrane surface.

THEORIES OF EMULSIFICATION

The most well-known theories include surface tension theory, the oriented wedge theory and the interfacial film theory.

Surface tension theoryIn accordance to surface tension theory of emulsification, the emulsifying agentscause a reduction in the interfacial tension of the two immiscible liquids, reducingthe repellent force between the liquids and withdrawing the attraction of liquidsfor their own molecules. In this way, the surfactants convert large globules intosmall ones and avoid small globules from coalescing into large ones.

The oriented Wedge theory of emulsionsAccording to this theory the oil-like or non- polar ends of the emulsifying agentsturn towards the oil and the polar ends towards the polar liquid. The orientedWedge theory of emulsions indicates that if the non-polar end of the emulsifyingagent is smaller, the emulsion will be oil-in water (o/w) and if the polar end issmaller, the emulsion will be water-in-oil (W/O)

The interfacial film theoryThe interfacial film theory suggests that the emulsifying agents make an interfacebetween the two immiscible phases of the emulsion, surrounding the droplets ofthe internal phase as a thin film. This film prevents the coalescence of thedispersed phase.

Types of emulsion

1. MACRO EMULSIONSA. Parenteral emulsions

B. Water-in-oil emulsions.

C. Oil- in-in-water /oral emulsions

D. Radio opaque

E. Fluorocarbon emulsion

2. MICRO EMULSION3. NANO EMULSION4. MULTIPLE EMULSION5.GEL EMULSION

1) Macro Emulsions :These emulsions comprise four possible types:

I - “oil-in-water” (O/W), II- “water-in-oil” (W/O), III-“water-in-water” (W/W), and IV- “Oil-in-oil” (O/O).

Emulsions of the W/W type are formed from aqueous solutions ofmixtures of incompatible polymers. They include systemscontaining polysaccharides, synthetic polymers, and proteins.The O/O emulsions consist of incompatible organic solventsstabilized by block copolymers with residues of differingsolubilities in the two components.The O/W emulsions are administered orally as well as parenterally,W/O emulsions are used mainly as diffusion barrier depots whengiven intramuscularly.

Depending on their end use, emulsions vary considerably in their composition, structure, and properties. Rheologically, for example, emulsions range from Newtonian and non-Newtonian liquids, including thixotropic systems, to gel-like solids. Surfactants are necessary in formulating stable emulsions of low viscosity and may be of low or high molecular weight. The surface activity of low molecular weight surfactants is sensitive to the composition of both phases of the system, and it is necessary to have a range of surfactants to match the hydrophilic-lipophilic balance (HLB) of a particular surfactant to the emulsion composition

A. Parenteral Emulsions:

“Emulsions that are injected in the body for the purpose of mitigation,

cure and diagnosis of a disease is known as Parenteral emulsions”

Uses Injectable emulsions are used mainly for Lipids or lipid-soluble materials. nutritional purposes delivery of vaccines, as drug carriers Diagnostic agents.

Preparation of Parenteral Emulsions:

Parenteral emulsions are subject to two important constraints:

particle size and Sterilization.

For intravenous emulsions, the particle size cannot be greater than 5µm without risking emboli in the capillaries. Average particle size for fat emulsions is less than 1µm

Method of preparation

Step1.Uniform particle size is achieved by homogenization at high temperatures under high pressure in homogenizer.

Step2.The resulting homogenized product is then autoclaved at 110°C for 40 min. Parenteral emulsions may be sterilized by filtration, provided the particle size is small enough to pass the filter. Sterilization of individual components and aseptic assembly is also feasible.

Application:

Parenteral nutrition:A major application of lipid emulsions is the delivery of fat in parenteralnutrition. Fat is a concentrated source of energy and can supply essential fatty acids.

Carriers for drugs and as targeted delivery systemsThe close resemblance of fat emulsion particles to chylomicrons, the

natural emulsion particles that transport ingested lipophiles such as triglycerides into the lymphatic and circulatory systems, suggests that fat emulsions can be used as carriers for drugs and as targeted delivery systems.

Prolonged release of drug Emulsions can affect the metabolism of the drug, which can in turn affect clearance of the particles from the blood. Positive prolonged release effects have, however, been noted for progesterone and corticosteroids.

Increased bioavailabilityIntralipid has been used to incorporate valinomycin, an antitumor agent

and it was found that a 20-fold lower dose was sufficient to produce the same effects as an aqueous suspension.

Decreased toxicityAmphotericin B administered as a lipid emulsion, in comparison with a 5% aqueous dextrose solution, gave a lower incidence of fever and nephrotoxicity and was as effective.

Stability:Instability of fat emulsions can arise from changes in particle size of the oil droplets leading to creaming and coalescence, or from changes in pH, hydrolysis of emulsifier, or oxidation of the oil. Emulsions cause enhanced stability furnished by a non-aqueous environment. Many drugs, including barbituric acid, diazepam, and anesthetics, have been dissolved in the oil phase and administered by all parenteral routes.

B. Oil in water emulsion

“If the oil droplets are dispersed throughout the aqueous phase, the emulsion is termed oil-in-water (O/W) with the help of emulsifying agent”.

Fats or oils for oral administration, either as medicaments in their own right, or as vehicles for oil soluble drugs, are always formulated as oil in water (O/W) emulsions.

Characteristics They are non greasy easily removable from the skin surface and they are used externally to provide cooling effect Used internally to also mask the bitter taste of oil. Water soluble drugs are more quickly released from O/W emulsion. O/W emulsion give a positive conductivity test as water External phase is a good conductor of electricity. The particle size of the dispersed phase commonly ranges from 0.1 to

100 µm Emulsifier stabilizes the system by forming a thin film and they is

present around the globules of dispersed phase

C. Water in oil emulsion“A system in which the water is dispersed as globules in the oil

continuous phase with the help of emulsifying agent is termed

water-in-oil emulsion (W/O)”.

Characteristics Water-in-oil emulsions will have an occlusive effect by hydrating

the stratum corneum and inhibiting evaporation of eccrinesecretions.

It do not give positive conductivity tests the external phase which is a poor conductor of electricity W/O

emulsion is also useful for cleansing the skin of oil soluble dirt they are greasy in texture although there greasy texture is not

always cosmetically acceptable

D. Radio opaque Emulsions

The substance which emits such radiation is called

radioactive and the process is called as radioactivity. For therapeutic and diagnostic purposes they are referred as ‘Radiopharmaceuticals’. All radio opaque are not radio-pharmaceutical unless they contain a radio isotope in their structure or formula. The element like uranium, radium, cobalt, phosphorous, iodine etc. are called radioactive elements.Development of nano-particulate systems exhibiting long circulation times in the blood pool, loaded with X-ray contrasting compounds, to be used as blood pool contrast agents in computed tomography.

RADIO OPAQUE CONTRAST MEDIA:Any agent or compound administrated to a patient to improve the visualization of an organ or tissue is called a contrast agent. Certain inorganic agents like iodine or barium salts can act as radio contrast media, by absorbing at soft tissues and these tissues becomes capable of absorbing X-rays. The barium sulphate salt is given to identify of ulcer in G.I.T. whenever ulcer is formed, broken mucosa retains barium sulphate and this spot (ulcer) is identified with the help of X-ray film. X-rays are electromagnetic radiations of short wavelength and have high penetrating power. The electrons of high atomic number element can interact with X-rays. The relative difference between the light and dark areas on a radiographic image reflects is called radiographic contrast.

D. Flourocarbon emulsion:The discovery that animals can survive breathing oxygen-saturated

silicones and certain perfluorinated liquids such as the isomers of perfluorotetrahydrofuran (FC-75) suggested that such inert substances might be useful as intravascular O2 and CO2 transporting agents. These are chemically inert synthetic molecules & are composed of fluorine & carbon & have ability to dissolve many gases e.g O2, CO2 etc.

Mechanism Of Drug Release: After i.v administration, droplets of these are taken up by reticulo-endothelial system, after which they are broken down & are taken into blood from where droplets are transported into lungs and excreted via inhalation. At present there is no metabolism in humans.

Applications: They are clinically evaluated as “Artificial oxygen carriers”. In future they will be used in the concept of ANH i.e acute normovalaemic

haemodilution, means it is used to augment oxygen delivery during surgery.

These are also used in treatment of diseases with compromised tissue oxygenation such as cerebral ischemia, MI, emergency, trauma etc.

2) MICROEMULSIONHoar and Schulman used the term micro emulsion (ME) in 1943 to define a transparent system obtained by titrating a turbid oil - in -water (o/w) emulsion with a medium chain alcohol, namely hexanol. Since then the term has been used to describe systems comprising a non polar component, an aqueous component, a surfactant, and a co-surfactant. While a co-surfactant is usually present, a ME can be formulated without a co-surfactant that is, using a single surfactant. It is important to point out that the term ME was (and occasionally is) used in the literature to describe various liquid crystalline systems (lamellar, hexagonal, and cubic), surfactant systems (micelles and reverse micelles), and even coarse emulsions that are micronized using external energy (sub micrometer emulsions).To avoid such confusion, Danielsson and Lindmann proposed the following definition: “Microemulsion is defined as a system of water, oil and amphiphilewhich is optically isotropic and a thermodynamically stable liquid solution.”

Structure and formation of microemulsion systems

A ME system can be one of three types depending on the composition:

Oil in water (o/w ME), in which water is the continuous medium; Water in oil (w/o ME), in which oil is the continuous medium, and Water - and - oil bicontinuous ME, in which almost equal amounts

of water and oil exist.

Phase Behavior:The phase behavior of simple micro-emulsion systems comprising oil, water and surfactant can be studied with the aid of ternary phase diagram (at fixed pressure and temperature) in which each corner of the diagram represents 100% concentration of the particular component.The relative amounts of these three components can be represented in a ternary phase diagram. Gibbs phase diagrams can be used to show the influence of changes in the volume fractions of the different phases on the phase behavior of the system.

Hypothetical Phase Regions of Micro Emulsion Systems:

From above figure, we can see that, With high oil concentration surfactant forms reverse micelles

capable of solubilizing water molecules in their hydrophilic interior.

Continued addition of water in this system may result in the formation of W/O microemulsion in which water exists as droplets surrounded and stabilized by interfacial layer of the surfactant / co-surfactant mixture.

At a limiting water content, the isotropic clear region changes to a turbid, birefringent one.

Upon further dilution with water, a liquid crystalline region may be formed in which the water is sandwiched between surfactant double layers.

Finally, as amount of water increases, this lamellar structure will break down and water will form a continuous phase containing droplets of oil stabilized by a surfactant / co-surfactant (O/W microemulsions)

Applications:

1- Oral Drug Delivery :Examples include Sendimmune neural which is commercial name for Cyclosporin A.Other examples include Paclitaxel & Simvastatin.

2- Transdermal Drug Delivery :A diverse range of drug molecules such as ketoprofen, apomorphine, estradiol, lidocaine, indomethacin and diclofenac, prostaglandin E 1 were incorporated as ME.

3- Parenteral Drug Delivery :Flubiprofen o/w ME systems were prepared and evaluated as vehicles for parenteral drug delivery. These systems were formulated using POE 20 sorbitan mono- laurate (Tween 20) as the surfactant.

4- Ocular Drug Delivery :Nanoemulsion is a type of emulsion sized between 20-200 nm with narrow distributions. They are transparent or translucent with a bluish coloration. So, the definition is different from that of sub-micron emulsions.

3) NANOEMULSIONSNanoemulsion is a type of emulsion sized between 20-200 nm with narrow distributions. These are very small sized as compared to simple emulsions. The high pressure of 25000 to 40,000 psi is required for its formulation as compared to simple emulsions which require 500 to 5000 psipressure.These are thermodynamically unstable but kinetically stable so they require high mechanical energy for their preparation supplied from high pressure homogenisers, microfluidizers, etc.

Applications of nano Emulsions:

1. Drug and gene delivery 2. Enhancement of skin permeation3. Extended drug release4. Antimicrobial activity5. Medical applications:

Parenteral route (propofol and diazepam) Ocular route (pilocarpine hydrochloride) Nasal route (peptide and vaccine) Topical route

4) MULTIPLE EMULSIONSMultiple emulsions are also known as emulsions of emulsions, liquid membrane system or double emulsion. The two major types of multiple emulsions are the w/o/w and o/w/o double emulsions. The most common multiple emulsions are of W/O/W types which are widely used for pharmaceutical purposes.

Formulation:

Modified Two Steps Emulsification: In step 1→ water phase is added into oil + surfactant mixture with

low HLB → homogenization done at 9500 rpm/min for 15 min →w/o emulsion is prepared.

In step 2→w/o emulsion is added into water +surfactant with high HLB → mechanical stirring done at 600 rpm/min for 30 min →w/o/w multiple emulsion.

Phase Inversion Technique (One Step Technique):

An increase in volume concentration of dispersed phase may cause an increase in the phase volume ratio, which subsequently leads the formation of multiple emulsions. The method typically involves the addition of an aqueous phase containing the hydrophilic emulsifier [Tween 80] to an oil phase consisted of liquid paraffin and containing lipophillic emulsifier (Span80). A well-defined volume of oil phase is placed in a vessel of pin mixer. An aqueous solution of emulsifier is then introduced successively to the oil phase in the vessel at a rate of 5 ml/min, while the pin mixer rotates steadily at 88 rpm at room temperature. When volume fraction of the aqueous solution of hydrophilic emulsifier exceeds 0.7, the continuous oil phase is substituted by the aqueous phase containing a number of vesicular globules among the simple oil droplets, leading to phase inversion and formation of W/O/W multiple emulsion.

Application of multiple emulsions:

1) Multiple emulsions in cancer therapy2) Vaccine/vaccine adjuvant 3) Oxygen substitute 4) Multiple emulsions in diabetes

Surfactant-coated insulin was dispersed in the oil by ultra-sonification, this dispersion was mixed with the outer water phase with a homogenizer.

5) As antidiabetic

Multiple emulsions of chloroquine, an anti-malarial agent has been successfully prepared and had been found to mask the bitter taste efficiently. Taste masking of chlorpromazine, an antipsychotic drug has also been reported by multiple emulsions.

6) Drug over dosage treatment

This system could be utilized for the over dosage treatment by utilizing the difference in the pH. For example Barbiturates, salicylates etc.

5) GEL EMULSIONS:

Gellified emulsions (Emulsion in gel) have emerged as one of the most interesting topical drug delivery and have dual control i.e as emulsion & as a gel. Emulgel is emulsions, either of the O/W or W/O type, which are gelled by addition of a gelling agent. Examples are antifungal agents. This antifungal agent is Itraconazole, which has both antifungal and antibacterial properties. It is applied locally in mild uncomplicated dermatophyte and other cutaneous infections.Gellified Emulsion is stable one and better vehicle for hydrophobic orWater insoluble drugs. Oil/water emulsions are most useful as water washable drug bases and for general cosmetic purposes, while water/oil emulsions are employed more widely for the treatment of dry skin and emollient.

Preparation of gellified emulsion:

The Gel in formulations were prepared by dispersing Carbopol 934 (thickner and suspending agent) in purified water with constant stirring at a moderate speed then the pH are adjusted to 6 to 6.5 using Tri Ethanol Amine (TEA). Theoil phase of the emulsion wereprepared by dissolving Span 20 inlight liquid paraffin while the aqueous phase was prepared by

dissolving Tween 20 in purified water. Methyl and Propyl parabenwas dissolved in propylene glycol whereas drug (Itraconazole)

is dissolved in ethanol and both solutions was mixed with the aqueousphase. Both the oily and aqueous phases were separately heated to70° to 80°C; then the oily phase are added to the aqueous phasewith continuous stirring until cooled to room temperature. And add Glutaraldehyde(as a sterilant) during of mixing of geland emulsion in 1:1 and to obtain the Gellified Emulsion.

Rheology & stability of emulsion: Rheological properties are affected by both conc. & temp. Stability

of gel emulsion at room temperature is increased by addition of NACl.

Applications:Uses include;1- These are used as antifungals to treat topical fungal infections e.g

itraconazol, miconazol nitrate emulsified gel.2-Terbinafin emulsion gel is an under eye emulsion gel & is used for:

Moisturising effect Provide comfort to delicate eye For skin repair To get rid of skin circles Provide protection against excessive dehydration.