SPECIALIZED PHARMACEUTICAL EMULSIONS

SPECIALIZED PHARMACEUTICAL EMULSIONS

1.INTRODUCTION:

1.1 DEFINITION

“A biphasic system consisting of two immiscible liquids, one of which (the dispersed phase) is finely and uniformly dispersed as globules throughout the second phase (the continuous phase).” Since emulsions are a thermodynamically unstable system, a third agent, the emulsifier is added to stabilize the system (Agarwal and Rajesh, 2007).

Emulsifier stabilizes the system by forming a thin film around the globules of dispersed phase (Javed et al., 2008).

Either the dispersed phase or the continuous phase may vary in consistency from that of a mobile liquid to semisolid (Alfred, 2005).

Thus, pharmaceutical emulsions range from lotions (low viscosity) to creams (high viscosity). The particle size of the dispersed phase commonly ranges from 0.1 to 100 μm (Agarwal and Rajesh, 2007).

1.2 COMPOSITION

An emulsion usually consists of following three components:

 Aqueous phase.

 Oily phase.

 Emulsifying agents.

AQUEOUS PHASE

The aqueous phase of an emulsion consists of purified or deionized water which contains water soluble drug, preservatives, coloring and flavoring agents.

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 formulation of emulsion should be prevented from autooxidation. For example: fixed oils are castor oil, cod liver oil, almond oil, liquid paraffin, shark liver oil, and volatile oil containing turpentine oil, sandal wood oil, cinnamon oil etc.

EMULSIFYING AGENTS

It is the component of emulsion which binds the two immiscible liquids, and stabilize the emulsion.

1.3 PARTICLE SIZE

The particle diameter of the dispersed phase generally extends from: 0.1-100μm.

Micro emulsions globules diameter: 0.1-0.2μm.

1.4 PURPOSE OF EMULSION:

Increased drug solubility; many drugs have limited aqueous solubility but have maximum solubility in oil phase of emulsion. 3

Increased drug stability; many drugs are more stable when incorporated into an emulsion rather than in aqueous solution.

Prolonged drug action; incorporation of a drug into an emulsion drugs with can prolong bioavailability, as with certain intramuscular injections preparation

Improved taste; drugs with unpleasant taste are more palatable and thus more conveniently administered in emulsion form.

Improved appearance; oily materials intended for topical applications are more appealing in emulsion form.

1.5 TYPES OF EMULSION

1. OIL IN WATER EMULSION

Pharmaceutical emulsions usually consist of mixtures of aqueous phase with various oils and waxes. If the oil droplets are dispersed throughout the aqueous phase, the emulsion is termed oil-in-water (O/W) as shown in Figure 1.

Characteristics

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 (Aulton, 1996).

They are non-greasy and are easily removable from the skin surface

They are used externally to provide cooling effect and 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, the external phase is a good conductor of electricity (Javed et al., 2008).

Examples

Vanishing cream

mayonnaise

vinaigrette

2. WATER IN OIL EMULSION

A system in which the water is dispersed as globules in the oil continuous phase is termed waterin-oil emulsion (W/O) as shown in Figure 2. 

Figure 2. W/O emulsion.

Characteristics

Water-in-oil emulsions will have an occlusive effect by hydrating the stratum corneum and inhibiting the evaporation of eccrine secretions.

W/O emulsion is also useful for cleansing the skin of oil soluble dirt, although its greasy texture is not always cosmetically acceptable (Aulton, 1996).

They are greasy and not water washable and are used externally to prevent evaporation of the moisture from the surface of skin e.g. cold cream.

Oil soluble drugs are more quickly released from W/O emulsion. They are preferred for formulation meant for external use like cream.

W/O emulsion is not given a positive conductivity tests, because oil is the external phase which is a poor conductor of electricity (Javed et al., 2008).

Examples

Butter

Propofol

Nivea cream

3. MULTIPLE EMULSIONS

A double emulsion (or multiple emulsion) is an emulsion of an emulsion. That is, it is an emulsion structure with coexisting water-in-oil (W/O) and oil-in-water (O/W) morphologies.

There are two main types of double emulsion:

water-in-oil-in-water (W/O/W)

oil-in-water in-oil (O/W/O).

The oil droplets of a W/O/W emulsion have water droplets dispersed within them, and the water droplets of an O/W/O emulsion contain dispersed oil droplets. 

Hence, double emulsion has three distinct bulk phases and two oil–water interfaces, as compared with the two bulk phases and single oil–water interface of an ordinary emulsion. The presence of these two kinds of interfaces means that two different emulsifying agents are typically required in order to formulate a double emulsion, one to stabilize the inner droplets (the primary emulsion) and another to stabilize the outer droplets (the secondary emulsion)

( Eric Dickinson et al ,2010)

Examples;

vancomycin prednisolone

Classification:

With optical microscopy method, multiple emulsions are classified as

Coarse (> 3 micrometer in diameter)

Fine (1-3 micrometer in diameter)

Micro-multiple emulsions (<1 micrometer in diameter)

4. MICRO EMULSION

Micro emulsions are systems consisting of water, oil and surfactant, which constitute a single optically isotropic and thermodynamically stable liquid solution.

There are two types of micro emulsion, one is O/W and the second is W/O micro emulsion. (Tadros, 1992) 

Emulsification process

Milk is a natural emulsion, which consists of fatty globules surrounded by a layer of casein, suspended in water. When a pharmaceutical emulsion is to be prepared the principal consideration is the same as that of milk.

(Christopher and Dawn, 2008).

1.6 GENERAL METHOD

Generally, 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 (Christopher and Dawn, 2008).

1. CONTINENTAL OR DRY GUM METHOD

Extemporaneously 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.(Christopher and Dawn,2008).

2. WET GUM METHOD

In 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 (Christopher and Dawn, 2008).

3. BOTTLE METHOD

This method may be used to prepare emulsions of volatile oils, or oleaginous substances of very low viscosities. It is not suitable for very viscous oils since they cannot be sufficiently agitated in a bottle. This method is a variation of the dry gum method.

One part powdered acacia (or other gum) is placed in a dry bottle and four parts oil are added. The bottle is capped and thoroughly shaken. To this, the required volume of water is added all at once, and the mixture is shaken thoroughly until the primary emulsion forms.

4. IN SITU SOAP METHOD

In this method no emulsifying agent is used, but one is formed "in situ" following a chemical interaction between the components.

It is also effective in preparing an olive oil and lime water emulsion, which is selfemulsifying. Equal parts of lime water and olive oil are added to the bottle and shaken. In the case of olive oil the free fatty acid is oleic acid that interacts with lime water to form calcium oleate that is emulsifying agent in this instance. 7

5. MEMBRANE EMULSIFICATION METHOD

It is a method, which is based on a novel concept of generating droplets “drop by drop” to produce emulsion. Here, a pressure is applied direct to the dispersed phase which seeps through a porous membrane into the continuous phase and in this way the droplets formed are then detached from the membrane surface due to the relative shear motion between the continuous phase and membrane surface (Nita et al., 2009).

1.7 TESTS FOR IDENTIFICATION OF EMULSION TYPE;

Several tests are used for identifying the emulsion type. Although, such tests may be applied rapidly, the results must be interpreted with caution. It may be possible that such tests can not indicate whether a multiple emulsion has been produced? Such controversies may be resolved by microscopic examination (Rawlins, 2005).

1. DILUTION / MISCIBILITY TEST;

Miscibility test involves the addition of continuous phase e.g. in case of O/W emulsion; the emulsion remains stable upon unlimited addition of water but will become unstable upon unlimited addition of oil, that is, the oil will separate. Vice versa is the case with W/O emulsion (Carter, 2007)

2. ELECTRICAL CONDUCTIVITY TEST; 

Water is a good conductor of electricity; hence, an emulsion with water continuous phase will readily conduct electricity while that with oil continuous phase will not (Aulton, 1988).

3. STAINING TEST / DYE SOLUBILITY TEST;

In this test, a small amount of water soluble dye, such as methylene blue is added to the emulsion, now if water is the continuous phase (O/W emulsion), dye will dissolve uniformly throughout the system. If oil is the continuous phase (W/O emulsion), dye will remain as cluster on the surface of the system 

(Alfred et al.,)

4. 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.

5. FLUORESCENCE TEST:

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

1.8 THEORIES OF EMULSIFICATION

Many theories have been advanced in an attempt to explain how emulsifying agents promote emulsification and maintain the stability of the emulsion. Although certain of these theories apply rather specifically to certain types of emulsifying agents and to certain conditions, they may be viewed in a general way to describe the manner in which emulsion may be produced and stabilized. Among the most prevalent theories are

1. SURFACE TENSION THEORY

2. THE ORIENTED-WEDGE THEORY

3.THE PLASTIC OR INTERFICIAL FILM THEORY.

All liquids have tendency to assume a shape having the minimal surface area exposed. For a drop of liquid , that shape is the sphere. It possess internal forces that tend to promote association of the molecules to resist distortion of the sphere. If two or more drops of the same liquid come into contact with one another, the tendency is for them to join or to coalesce, making one larger drop having a smaller surface area than the total surface area of the individual drops. This tendency of 

 liquid may be measured quantitatively, and when the surrounding of the liquid is air, it is referred to as the liquid’s surface tension. When the liquid is in contact with a second liquid in which it is insoluble, the force causing each liquid to resist breaking up into smaller particles is called interfacial tension. Substances that reduce this resistance encourage a liquid to break up into smaller drops or particles. These tension lowering substances are surface active or wetting agents.

1.SURFACE TENSION THEORY:

The use of surfactants as emulsifiers and stabilizers lowers the interfacial tension of the two immiscible liquids, reducing the repellent force between the liquids and diminishing each liquid attraction for its own molecules. Thus , the surfactants facilitate the breaking up of large globules into smaller ones, which then have a lesser tendency to reunite or coalesce.

2.ORIENTED –WEDGE THEORY:

This assumes mono molecular layers of emulsifying agent curved around a droplet of the internal phase of the emulsion. This based on the presumption that certain emulsifying agents orient themselves about and within a liquid in a manner reflective of their solubility in that particular liquid. In a system containing two immiscible liquids, presumably the emulsifying agent is preferentially soluble in one of the phases and is embedded more deeply and tenaciously in that phase than the other. Because many molecules of substances upon which theory is based(soaps) have a hydrophilic head and hydrophobic tail, the molecule 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 envisioned for the molecules causes either oil globules or water globules to be surrounded. Generally , an emulsifying agent having a greater hydrophilic than hydrophobic character will promote an O/W emulsion and a W/O emulsion results from use of an emulsifying agent that is more hydrophobic than hydrophilic. Putting it another way, the phase in which emulsifying agent is more soluble will become the continuous phase. Although this theory may not represent a totally accurate depiction of the molecular arrangement of the emulsifier molecules, the concept that water soluble emulsifiers generally do form o/w emulsion is important and is frequently encountered in practice.

3.PLASTIC OR INTERFACIAL FILM THEORY:

It places the emulsifying agent at the 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 contact and coalescing of the dispersed phase ; the tougher and more pliable the film, the greater the stability of the emulsion. Naturally enough of the film forming material must be available to coat the entire surface of each drop of the internal phase. Here again , the formation of an o/w emulsion depends on the degree of solubility of the agent in the two phases, with water soluble agents encouraging o/w emulsion and oil soluble emulsifiers the reverse.

In actuality, it is unlikely that a single theory of emulsification can explain the means by which the many and varied emulsifiers promote emulsion formation and stability. It is more than likely that even within a given emulsion system, more than one of the aforementioned theories play a part. For instance, 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. No doubt certain emulsifiers are capable of both tasks.

2. EMULSIFYING AGENTS:

2.1 DEFINITION

“the chemical agents that are used to reduce the coalescence between the 2 immiscible liquids are called emulsifying agents” 

2.2 PROPERTIES OF EMULSIFYING AGENT:

 It must be compatible with formulation ingredients.

 Must not interfere with stability and efficacy of the product.

 should be non toxic.

 should be stable and not deteriorate in the prepration.

 Should be odourless, colourless and tasteless

 Should increase the viscosity of the product.

2.3 MECHANISM OF EMULSIFYING AGENTS:

When 2 immiscible liquids are mixed they form separate layers and the surface free energy of the system is increased due to interfacial tension, different densties of 2 phases and large surface area of dispersed phase. To stabilize it emulsifying agent is added, the emulsifying agent first adsorb at the surface of interface and when interface becomes saturated and no further space remaining then emulsifying agent moves toward the bulk of the solution. The emulsifying agent make the two phases miscible in a manner that the lipophilic portion of it is towards oily phase and hydrophilic towards the aqueous phase. Miscelles are formed at CMC consisting of 50-150 molecules of emulsifying agent and emulsification occurs. So according to theories emulsifying agent stabilizes the emulsion by

 Reducing surface tension

 Reducing interfacial tension

 form film around the droplet

 Provides electric potential

2.4 CLASSIFICATION OF EMULSIFYING AGENTS:

There are many types of emulgent available but for convenience they can be devided into two main classifications:-

 Synthetic or semi synthetic surface active agent

 Naturally occurring materials and their derivatives

These devisions are quite arbitrary and some materials may justifiably be placed in more than one category.

2.4.1 SYNTHETIC AND SEMISYNTHETIC SURFACE ACTIVE AGENTS:

There are 4 main categories of these materials:

a) Anionic

b) Cationic

c) Non ionic

d) Amphoteric (lecithin)

a) Anionic surfactants:

In aqueous solution these compounds dissociate to form negatively charged anions that are responsible for there emulsifying ability. They are widely used because of their cheapness but because of their toxicity are only used for externally applied preparations.

1: Alkali metals and ammonium soap:

Emulgents in this group consist mainly of the sodium< potassium or ammonium salts of long chain fatty acids such as sodium stearate.

They produce stable emulsion but because in acidic conditions these materials will precipitate out as free fatty acids these materials are most efficient in alkaline medium. this type of emulgent can also be formed by reacting an alkali such as potassium , sodium or ammonium hydroxide with a fatty acid. The latter may be a constituent of a vegetable oil, oleic acid and ammonia for example 

are reacted together to form a soap responsible for stabilizing white liniment these emulgents are incompatible with polyvalent cations often causing phase reversal and it is therefore necessary that deionized water is used in their preparation.

2:Soap of divalent and trivalent metals:

Only the calcium salts are commonly used and often formed in situ during prepration of the product by interacting the appropriate ftty acid with calcium hydroxide. For example oleic acid is reacted with calcium hydroxide to produce calcium oleatewhich is emulsifieng agent for both zinc cream BP and some formulations of oily calamine lotion.

These emulgents will only produce W/O emulsions.

3:Amine soaps:

A number of amines form salts with fatty acids. One of most important of these is based on triethanolamine and widely used in both pharmaceutical and cosmetic products. For example triethanolamine form stable O/W emulsion and is formed by reaction between triethanolamine and appropriate fatty acid.

4:Sulfated and sulfonated compounds:

An example is sodium lorayl sulfate which is widely used to produce O/w emulsions. It is used with cetostearyl alcohol to produce emulsifying wax which stabilize such preprations as aquous cream.

Sulfonated compounds are much less widely used as emulgent . materials of this class include sodium dioctylsulfosuccinate and are more often used as wetting agent or for their detergency.

b) Cationic surfactants:

In aqueous solutions these materials dissociate to form positively charged cations that provide the emulsifying properties. The most important group of cationic emulgents consist of the quaternary ammonium compounds. Although these compounds are used for their disinfectant and preservative properties they are also useful O/W emulsifiers.

Because of toxicity of cationic surfactants they tend to be used only for the preparation of antiseptic creams where the cationic nature of the emulgent is also responsible for the products antiseptic properties.

Cetrimide is one of the most useful of these emulgent and used at a concentration of 0.5% with 5% cetostearyl alcohol for the formulation of cetrimide cream.

c) Non-ionic surfactants:

These products range from oil soluble compounds stabilizing w/o emulsions to water soluble materials giving o/w products. They have low toxicity and irritancy therefor be used for orally and parenterally administered preparations. They also have greater degree of compatibility then cationic and anionic emulgents.

Most non-ionic surfactants are based on:

A fatty acid, the hydrocarbon chain of which provides the hydrophobic moiety

An alcohol, which provides the hydrophilic part of the molecule

By varying the relative proportions of the hydrophilic and hydrophobic grouping many different products can be obtained.

1.glycol and glycerol esters:

glyceryl monostearate is a strongly hydrophobic material that produce weak w/o emulsions. The addition of small amount of sodium, potassium or triethanolamine salts of suitable fatty acids will produce a self-emulsifying glyceryl monostearate which is a useful o/w emulsifier. Self-emulsifying monostearin is glyceryl monostearate to which anionc soaps have been added. This 

combination is used to stabilize hydrocortisone lotion. Other examples include glyceryl monooleate, diethylene glycol monostearate and propylene glycole monooleate.

2:Sorbitan esters:

These are produced by the esterification of one or more of the hydroxyl groups of the sorbitan with either oleic, palmitic or stearic acid.

This range of surfactants exibit lipophilic properties and tend to form w/o emulsions.

3. Polysorbates:

Polyethylene derivatives of the sorbitan esters give us polysorbates.

Polysorbates are generally used in conjunction with the corresponding sorbitan ester to form a complex condensed film at the o/w interface.

Other non ionic oil soluble materials such as glyceryl monostearate ,cetyl or stearyl alcohol or propylene glycole monostearate can be incorporated with polysorbates to produce self emulsifying preprations e.g polawex containas cetyl alcohol with a polyoxyethylene sorbitan ester.

4.Fatty alcohol polyglycol esters:

These are condensation products of polyethylene glycol and fatty alcohols.

Perhaps the most widely used is macrogol cetostearyl ether or cetomacrogol which is polyethylene glycole monocetyl ether. This is very useful water soluble o/w emulgent because of high water solubility it is necessary to introduce an oil soluble auxiliary emulsifier when formulating emulsions’

5.Fatty acid polyglycol esters;

The stearate esters of polyoxyl stearates are the most widely used of this type of emulgent. Polyoxyethylene 40 stearate is a water soluble material often used with stearyl alcohol to give oil in water emulsion.

6.Poloxakols:

Poloxacols are polyoxyethylene/polyoxypropylene copolymers and a comprise a very large group of compounds. Some of which are used as emulsifying agent for intravenous emulsions.

7.Heigher fatty alcohols:

The hexadecyl and octadecyl members of this series of saturated aliphatic monohydric alcohols are useful auxillary emulsifying agents. Part of their effect come from their ability of increasing viscosity thereby reducing creaming. Cetostearyl alcohol also form interfacial film with hydrophilic surface active agents, such as sodium lauryl sulfate, cetrimide or cetromacrogol 1000 and so stabilize o/w emulsions.

2.4.2 NATURALLY OCCURRING MATERIALS AND THEIR DERIVATIVES:

They have 2 main disadvantages:

They show considerable batch to batch variation in composition and hence in emulsifying properties

Many are susceptible to bacterial mould growth.

For these reasons they are not widely used in prepration of products requiring longer half life.

Natural polysaccharides:

The most important emulsifying agent in this group is acacia. This stabilizes o/w emulsion by forming strong multimolecular film around each oil globule and so coalescence is retarded by the presence of a hydrophilic barrier between the oil and water phases.

Because of its low viscosity creaming will occur readily and therefore a suspending agent such as tragacanth or sodium alginate can also be included.

Semi-synthetic polysaccharides: 

In order to reduce the problems associated with batch to batch variation semisynthetic derivatives are available in o/w emulgents or stabilizers.

Several grades of methylcellulose and carmellose sodium are available and exert their action in a similar way to that of acacia. Methylcellulose 20 for example is used at a concentration of 2% to stabilize liquid paraffin oral emulsion.

3.EQUIPMENTS FOR EMULSION PREPRATION:

3.1 EQUIPMENTS FOR SMALL SCALE PREPARATION:

different techniques are used to prepare emulsion on small scale some of which are described below:

3.1.1 MORTAR AND PESTLE:

The mortar and pestle can be used for small scale prepration of emulsion in labs and pharmacy and it is one of the simplest method to be used.

Advantages:

low cast

simplest operation

Disadvantage:

Final particle size is larger than other equipments

3.1.2 AGITATOR:

Ordinary agitation or shaking may be used the emulsion. This method is frequently applied by the pharmacist particularly in the emulsification of easily dispersed low viscosity oils. Under certain conditions intermittent shaking is considerably more effective then ordinary continuous shaking. Continuous shaking break not only the phase to be dispersed but also the dispersion medium thus impair emulsification.

3.1.3 MECHANICAL MIXERS:

Emulsions may be prepared by using one of the several mixers which are available. Propeller and impeller type mixers that have a propeller attached to a shaft driven by an electric motor are convenient and portable and can be used for stirring and emulsification. A turbine mixer has a number of blades that may be straight or curved with or without a pitch , mounted on ashaft. The turbine tends to give more shear than propeller and is used for prepration of high viscosity emulsions.

Small electric mixers may be used to prepare emulsion at the prescription counters. They save time and energy and produce satisfactory emulsions, when emulsifying agent is acacia or agar.

3.2 EQUIPMENTS FOR LARGE SCALE PREPRATION:

Several equipments are used :

3.2.1 COLLOID MILLS:

High shear colloid mills or rotor/stator mixers are widely used for emulsion prepration. The principle of operation of the colloid mill is the passage of the mixed phases of the emulsion formula between a stator and a high speed rotor revolving at speed of 2000 to 18000 rpm.the emulsion mixture while passing between the rotor and stator is subjected to tremendous shearing action which effects a fine dispersion of uniform size. The shearing action usually rise the temperature of emulsion so a coolant is used to absorb the excess heat.

Advantage:

Very high shearing force can be generated

Very fine particles can be prepared

Useful for prepration of relatively viscous emulsions 

3.2.2 HOMOGENIZER:

Impeller type of equipment frequently produces a satisfactory emulsion however for further reduction in particle size homogenizer may be employed. Homogenizer may be used in one of the 2 ways:

The ingredients in the emulsion are mixed and then passed through the homogenizer to produce the final product

A coarse emulsion is prepared in some other way and then passed through a homogenizer for the purpose of decreasing the particle size and obtaining a greater degree of uniformity and stability.

It is postulated that circulation and turbulence are responsible mainly for the homogenization that take place.

3.2.3) ULTRASONIC DEVICES:

The preparation of emulsion by the use of ultrasonic vibrations is also possible. An oscillator of high frequency 100-500 kHz is connected to two electrodes between which is placed a piezoelectric quartz plate. The quarts plate and electrodes are immersed in an oil bath and when the oscillator is operating , high frequency waves flow through the fluid. Emulsification is accomplished by simply immersing a tube containing the emulsion ingredients into this oil bath.

3.2.4) MICROFLUIDIZER:

Microfluidizers have been used to produced very fine particles. The process subjects the emulsion to an extremely high velocity through microchannels into an interaction chamber as a result particles are subjected to shear, turbulence, impact and cavitation. Two advantages of this type of equipment are lack of contamination in the final product and ease of production scale up.

4. DETERMINATION OF HLB :

William Griffin, in the late 1940s, introduced the Hydrophilic-Lipophilic Balance system (HLB)as a way of figuring out which emulsifier would work best with the oil phase of an emulsified product. All emulsifiers have a hydrophilic head (water loving) that is generally composed of a water soluble functional group and a lipophilic tail (oil loving) generally composed of a fatty acid or fatty alcohol.The proportion between the weight percentages of these two groups in a surfactant molecule is an indication of the behaviour that may be expected from that product. An emulsifier that is lipophilic in character is assigned a low HLB number and an emulsifier that is hydrophilic in character is assigned a high number. The midpoint is approximately ten and the assigned values have ranged from one to forty.

4.1) THEORY

The theory behind HLB is that emulsifier having low HLB value tend to be oil soluble and materials having high values tend to be water soluble. However, this doesn’t always be

right, e.g., two emulsifiers may have the same HLB and exhibit different solubility characteristics. Further, one should take a point into consideration that chemical type

alone doesn’t establish hydrophilic-lipophilic balance. Thus, soaps may range from strongly hydrophilic for sodium laurate to strongly lipophilic for aluminium oleate. 15

4.2) DETERMINATION OF HLB BY CALCULATION

Calculation of HLB value of surfactant is very important in product quality and yield points of view. HLB values can be calculated theoretically or may be determined by experimentally. The experimental method is very long and laborious and was described long back ago by William

Griffin in 1949. Formulas for calculating HLB values may be based on either analytical or composition data. For most polyhydric alcohol fatty acid esters approximate values may

be calculated with the formula:

These formulas are satisfactory for non-ionic surfactants of many types. However, non-ionic surfactants containing propylene oxide, butylene oxide exhibit behaviour which has

not been related to composition. In addition, the HLB values of ionic surfactants do not follow a weight percentage basis because even though the hydrophilic portion is low molecular

weight the fact that its ionization lends extra emphasis to that portion and therefore makes the product more hydrophilic. For these products, the experimental method must be used.

4.3) DETERMINATION OF HLB “REQUIREMENT”

HLB “requirement” is the amount of surfactant required to make an oil to remain in solution. Variation of the proportion of the blended emulsifiers has been preferred to obtain best

results. When two emulsifiers of known HLB are thus blended for use with a given oil there is an optimum ratio that best emulsification and the HLB at this ratio is said to be the required HLB for the oil (to give that type of emulsion, whether O/W, W/O solubilisation, etc.). This is

expressed by the equation.

HLB(OIL)=WA*HLB( A )+WB *HLB (B) / WA+WB

Where, WA= the amount (weight) of the 1st emulsifier (A)used.

WB= the amount (weight) of the 2nd emulsifier (B) used at the optimum ratio giving the best emulsion.

HLBA, HLBB= the assigned HLB values for

emulsifiers A and B.

HLBoil= the “required HLB” of the oil for the type of emulsion being studied.

4.4) APPLICATIONS OF SURFACTANTS DEPENDING ON HLB

The HLB system is very useful to distinguish the surfactants

according to their applications. Generally, the applications

for nonionic surfactants within the following HLB ranges are

as follows 

5. CREAMING AND SEDIMENTATION:

5.1) CREAMING:

Creaming is the upward movement of the droplets relative to the continuous phase. It occurs when dispersed phase is less dense than the continuous phase as in O/W type emulsion.

5.2) SEDIMENTATION:

Sedimentation is defined as downward movement of droplets relative to the continuous phase. If internal phase is heavier than the external phase, globules will tend to settle down causing sedimentation as in the case of W/O type emulsion.

Creaming is reversible. Upon shaking creamed portion of the emulsion can be redistributed homogenously but still creaming and sedimentation are often undesirable due to following reasons: If insufficient shaking is employed before each dose improper dosage of the internal phase may result. Not acceptable by the consumer

How to overcome :

By using stokes equation,

So there are 3 factors that govern rate of settling of droplets: I. Diameter of suspended droplets II. Viscosity of suspending medium III. Difference of densities between dispersed phase and the dispersion medium. But we can use only first two factors to reduce rate of creaming or sedimentation. 1. Reduction of particle size as rate of movement is a square root function of the particle diameter. Particle diameter can be reduced up to 0.1μm. 2. Most frequent approach is to raise viscosity of the continuous phase for this we can use viscosity improver or thickening agent for example Methylcellulose, tragacanth 

or Sodium alginate. But we can only increase thickness up to the acceptable limit so that emulsion can be poured easily. 3. Theoretically if internal and external phase densities are same there would be no creaming or sedimentation but it’s not possible practically as temperature change density.

5.3) COALESCENCE AND BREAKING: COALESCENCE: Complete fusion of droplets to decrease number of droplets that can lead to breaking of emulsion. Aggregation precedes coalescence in emulsion; however coalescence does not necessarily follow from aggregation. Coalescence is irreversible as in coalescence protective sheath of emulsifier around dispersed droplets no longer exist. BREAKING: Separation of internal phase and separation of that phase into a layer is called breaking and emulsion is called cracked or broken.

How to overcome coalescence? Coalescence can be overcome by using combination of surfactants that provide certain advantages: Ø-water interface Ø of elastic film that will not rupture upon collision of emulsion droplets Additional beneficial effect of mixed emulsifier films could result from an increase in viscosity of the interfacial emulsifier film. A viscous interfacial film could enhance emulsion stability because thinning of the film at the point of droplet to droplet contact would be inhibited. 5.4) 

INVERSION: An emulsion is said to be inverted when it changes from O/W type to W/O type or vice versa. Following factors can cause inversion of emulsion: 

Ø-for example an O/W emulsion having sodium stearate as the emulsifier can be inverted by the addition of calcium chloride, because the calcium stearate formed is a lipophilic emulsifier and favors the formation of a W/O product. Ø two phases is being cooled. This takes place presumably because of the temperature dependent changes in the solubilities of the emulsifying agents. How to avoid inversion? Ø exceed 50% of the total volume of the emulsion. Ø 20

6. EVALUATION OF EMULSION STABILITY:

To speed up stability evaluation of emulsion formulator commonly places the emulsion under some sort of stress. Stress conditions normally employed for evaluating the stability of emulsions include: 1. Aging and temperature 2. Centrifugation 3. Agitation

6.1)AGING AND TEMPERATURE: Ø varying period of time at temperatures that are higher than normally encountered. 

Ø is cycling between 4 and 45°C.This type of cycling approaches realistic shelf conditions but places emulsion under enough stress to alter various emulsion parameters. ØTemperature changes cause varied effects on following parameters of emulsion: ity    ØAn ‘’acceptable’’ emulsion should survive two or three freeze thaw cycles between - 20 and 25°C with no visible signs of instability similarly a stable emulsion should survive six or eight heating/cooling cycles between 4 and 45°C with storage at each temperature for not less than 48 hours. 

6.2CENTRIFUGATION: Ø predicted rapidly by observing the separation of dispersed phase due to either creaming or coalescence when the emulsion is exposed to centrifugation. Ø therefore accelerates separation. Ø-radius centrifuge for a period of 5 hours is equivalent to the effect of gravity for about one year. Ø- 3,000 rpm at room temperature. 3. Agitation: Ø coalescence of droplets take place owing to their Brownian movements. Simple mechanical agitation can contribute to the energy with which two droplets impinge upon each other and hence may lead to coalescence and ultimately breaking of emulsion. Excessive shaking or homogenization also interferes with the formation of emulsion. Øy agitation for 24 to 48 hours on a reciprocating shaker approximately 60 cycles/minute at room temperature and at 45°C.

7. ADVANCED PHARMACEUTICAL EMULSIONS:

7.1) MICRO EMULSIONS

7.1.1) HISTORICAL BACKGROUND :

The microemulsion concept was introduced as early as 1940’s by Hoar and Schulman who generated a clear single-phase solution by titrating a milky emulsion by hexanol. Schulman and co-worker (1959) subsequently coined the term microemulsion.

7.1.2) DEFINITION :

“ Micro-emulsions is homogenous, transparent, thermodynamically stable dispersions of water and oil, stabilized by a surfactant, usually in combination with a co-surfactant.” 

7.1.3) ALTERNATIVE NAMES :

Microemulsions are also called as,

Transparent emulsion, Swollen micelle, Micellar solution ,Solubilized oil

7.1.4) COMPOSITION OF MICRO-EMULSION :

Microemulsions is defined as transparent dispersion consisting of,

1. Oil

2. Surfactant

3. Co-surfactant

4. Water

7.1.5) ADVANTAGES:

o Increase the rate of absorption

o Increase bio-availability

o Helpful in taste masking

o Eliminates variability in absorption

o Helps in solubilizing lipophilic drugs

7.1.6) DISADVANTAGES:

o Use of large concentration of surfactant and co-surfactant necessary for the stabilizing micro droplets.

o Limited solubilizing capacity for high melting substances.

o Microemulsion stability is influenced by environmental parameters such as, temperature & ph. These parameters change upon microemulsion delivery to the patients.

7.1.7) TYPES OF MICROEMULSIONS :

Microemulsions are of 3 types.They are

1) O/W Microemulsion

2) W/O Microemulsion

3)Bi-continuous microemulsion 

o O/W Microemulsion where in droplets are dispersed in the continuous aqueous phase.

o W/O Microemulsion where in water droplets are dispersed in the continuous oil phase.

o Bi-continuous microemulsion where in micro domains of oil & water are inter dispersed within the system.

In all the three types of microemulsions,the interface is stabilized by an appropriate combination of surfactants and/or co- surfactants.

7.1.8) PREPARATION METHODS OF MICROEMULSIONS :

Following are the different methods used for the preparation of the microemulsions :

1) Phase titration method

2) Phase inversion method

Phase-titration method :

1. Dilution of an oil-surfactant mixture with water.[W/O] 2. Dilution of a water surfactant mixture with oil.[O/W] 3. Mixing of all components at once, in some systems, the order of ingredients addition may determine whether a microemulsion forms are not.

Phase-inversion method :

Temperature range in which an o/w microemulsions inverts to a w/o type. Using non-surfactants: polyoxyethylene are very suspectible to temperature. with increasing the temperature, the polyoxyethylene group becomes dehydrated, altering critical packing parameter which results in the phase inversion. For ionic surfactants: increasing temperature, increase the electrostatic repulsion between the surfactant headgroups thus causing reversal of film carvature. Hence, the effect of temperature is opposite to the effect seen with non-ionic surfactants.

7.1.9) FACTORS AFFECTING MICROEMULSION FORMATION :

1. Packing ratio

2. Property of surfactant

3. Property of oilphase

4. Temperature

5. Chain length

6. Nature of co-surfactant

APPLICATIONS :

1) Oral delivery system 2) Parenteral delivery system 3) Ophthalmic delivery system 4) Microemulsions in detergency 5) Microemulsions in cosmetics 6) Microemulsions in foods 

:

CONCLUSION : Microemulsions are potentially quite powerful alernative carrier system for delivery because of high solubilization capacity, transparency, thermodynamic stability, ease of preparation, and high diffusion and absorption rates through skin, when compared to solvent without the surfactant system. A number of factors must be considered when using microemulsions as drug delivery system such as surfactant, co-surfactant, oils, pH, HLB, temperature etc.

Figure: Microemulsion and Std Emulsion

7.2 MACROEMULSION

Macroemulsions are kinetically stabilized mixtures of at least two immiscible liquids where one of the liquids has droplets with a diameter greater than 0.1 μm. Macroemulsions scatter light effectively and therefore appear milky, because their droplets are greater than a wavelength of 

light. As with all emulsions, one phase serves as the dispersing agent. It is often called the continuous or outer phase. The remaining phase(s) are disperse or inner phase(s), because the liquid droplets are finely distributed amongst the larger continuous phase droplets.This type of emulsion is thermodynamically unstable, but can be stabilized for a period of time with applications of kinetic energy. Surfactants (emulsifiers) are used to reduce the interfacial between the two layers, and induce macroemulsion stability for a useful amount of time.

IUPAC definition

Emulsion in which the particles of the dispersed phase have diameters from approximately 1 to 100 μm.

Macro-emulsions comprise large droplets and thus are "unstable" in the sense that the droplets sediment or float, depending on the densities of the dispersed phase and dispersion medium. Separation of the dispersed and continuous phasesusually occurs within time periods from a few seconds to a few hours, depending upon the viscosity of the fluid medium and the size and density of the droplets.

7.2.1) TYPES OF MACROEMULSION

Macroemulsions can be divided into two main categories based on if they are a single emulsion or a double or multiple emulsion group. Both categories will be described using a typical oil (O) and water (W) immiscible fluid pairing. Single emulsions can be sub divided into two different types. For each single emulsion a single surfactant stabilizing layer exists as a buffer in between the two layers. In (O/W) oil droplets are dispersed in water. On the other hand (W/O) involves water droplets finely dispersed in oil. Double or multiple emulsion classification is similar to single emulsion classification, except the immiscible phases are separated by at least two surfactant thin films. In a (W/O/W) combination, an immiscible oil phase exists between two separate water phases. In contrast, in an (O/W/O) combination the immiscible water phase separates two different oil phases

Figure: (A) o/w (B) w/o (C) w/o/w (D) o/w/o

Macroemulsions are, by definition, not thermodynamically stable. This means that from the moment they are created, they are always reverting to their original, immiscible and separate state. The reason why Macroemulsions can exist however, is because they are kinetically stable rather than thermodynamically stable. This means that while they are continuously breaking down, it is done at such a slow pace that it is practically stable from a macroscopic perspective.

7.2.2) STABILITY

Stability of the Macroemulsions are based on numerous environmental factors including temperature, pH, and the ionic strength of the solvent. 

7.2.3) USES:

Macroemulsions have nearly endless uses in scientific, industrial, and household applications. They are widely utilized today in automotive, beauty, cleaning and fabric care products as well as biotechnology and manufacturing techniques.[5]

Macroemulsions are often chosen over microemulsions for automotive and industrial applications because they are less expensive, easier to dispose of, and their tendency to demulsify more quickly is often desirable for lubricants. Soluble oil lubricants, usually containing fatty oil or mineral oil in water, are ideal for high speed and low pressure applications. They are often used for friction reducing needs and metalworking.[6]

Many skin care products, sun screens, and fabric softeners are made from silicone macroemulsions. Silicone's is chosen because of its non-irritating and lubricating properties. Different combinations of macroemulsions and surfactants are the subject of a wide range of biological research, especially in the area of cell cultures.

The following table outlines a few examples of macroemulsions and their applications: Macroemulsion	Continuous Phase	Dispersed Phase	Application	Surfactant
Diesel Fuel and Water	Diesel	Water	Reducing fuel emissions[6]	Nonionic surfactants based on aliphatic hydrocarbon tails (examples: alcohol ethoxylates, fatty acid ethoxylates, sugar esters of fatty acids)[10]
Silicone and Water	Water	Silicone	Fabric Softener,[5]Cosmetics[11]	Nonionic surfactants (example: silicone copolyol)[11]
Alcohol and Water	Water	Alcohol	Purifying contaminated ground water[9]	Food or pharmaceutical quality agents similar to those used in whipped toppings and shampoos (examples: Polysorbate-20, Tween or Span)[9]
Isooctane and Water	Isooctane	Water	Housing cell cultures[8]	Have bactericide or bacteriostatic properties (example: Lecithin, a phospholipid found in many animals naturally)[8]

7.3 NANOEMULSIONS

7.3.1) INTRODUCTION

The term "Nanoemulsion" refers to a thermodynamically unstable dispersion of two immiscible liquids, such as oil and water, stabilized by an interfacial film of surfactant molecules.

The dispersed phase typically comprises small particles or droplets, with a size range of 5 nm-200 nm, and has very low oil/water interfacial tension.

Three TYPES OF NANOEMULSIONS are most likely to be formed depending on the composition:

 1-Oil in water Nanoemulsions wherein oil droplets are   dispersed in the continuous  aqueous phase.

 2-water in oil Nanoemulsions wherein water droplets are   dispersed in the continuous  oil phase.

 3-Bi-continuous Nanoemulsions wherein microdomains of oil and water are interdispersed within

 the system.

7.3.2) CLASSIFICATION OF SURFACTANTS:

 Nonionic- Fatty alcohols, glycerol esters, fatty acid esters.

 Anionic-Contain carboxylate groups. Soaps, Sulfonates, Divalent ions.

 Cationic- Amines and quaternary ammonium compounds. Cetyl trimethyl ammonium bromide.

7.3.3) ADVANTAGES OF NANOEMULSION OVER OTHER DOSAGE FORMS

 Increase the rate of absorption.

 Eliminates variability in absorption.

 Helps solublize lipophilic drug.

 Provides aqueous dosage form for water insoluble drugs.

 Increases bioavailability.

 Various routes like topical, oral and intravenous can be used to deliver the product.

 Rapid and efficient penetration of the drug moiety Provides protection from hydrolysis and oxidation as drug in oil phase in O/W Nanoemulsion is not exposed to attack by water and air.

 Liquid dosage form increases patient compliance.

 Less amount of energy requirement.

 The use of Nanoemulsion as delivery systems can improve the efficacy of a drug, allowing the total dose to be reduced and thus minimizing side effects.

7.3.4) DISADVANTAGES OF NANOEMULSION BASED SYSTEMS

 Use of a large concentration of surfactant and cosurfactant necessary for stabilizing the nanodroplets. Limited solubilizing capacity for high-melting substances.

 Expensive

 Nanoemulsion stability is influenced by environmental parameters such as temperature and pH. These parameters change upon Nanoemulsion delivery to patients.

7.3.5) FACTORS TO BE CONSIDERED IN PREPARATION

Three important conditions:

 Surfactants must be carefully chosen so that an ultra low interfcial tension (< 10-3 mN/m) can be attained at the oil / water interface which is a prime requirement to produce Nanoemulsions.

 Concentration of surfactant must be high enough to provide the number of surfactant molecules needed to stabilize the microdroplets to be produced by an ultra low interfacial tension.

 The interface must be flexible or fluid enough to promote the formation of Nanoemulsions.

7.3.6) METHODS OF PREPARATION

 High pressure homoginization:

 Microfluidization

High pressure homoginization:

This method used a high very high presssure homoginizer/piston homoginization to produce very small droplet

size up to 1nm.

Microfluidization:

It is patented mixing technology which uses the microfluidizer.

The device uses a high pressure positive displacement pump which forces the product through interaction channel which contains ‘microchannels’.

The product flows through a microchannels on to an impingement resulting in a very fine particle/droplet size.

The aqueous and oily phase are processed in an in line homoginizer to yield a coarse emulsion. Then it is further proceed to microfluidizer to obtain a nanoemulsion.

The coarse emulsion is passed through the interaction channel repeatedly to yield a desired size nanoemulsion.

7.3.7) APPLICATIONS OF NANOEMULSIONS

Parenteral delivery ,Oral drug delivery,Topical drug delivery,Ocular and pulmonary delivery & Nanoemulsions in biotechnology

Parenteral delivery:

Nanoemulsion formulations have distinct advantages over macroemulsion systems when delivered parenterally because of the fine particle Nanoemulsion is cleared more slowly than the coarse Nanoemulsion formulations offer the several benefits over conventional oral formulation for oral administration including increased absorption, improved clinical potency,and decreased drug toxicity. Therefore, Nanoemulsion have been reported to be ideal delivery of drugs such as steroids, hormones, diuretic and antibiotics.

A Nanoemulsion formulation of cyclosporine, named Neoral® has been introduced to replace Sandimmune®, a crude oil-in-water emulsion of cyclosporine formulation. Neoral® is formulated with a finer dispersion, giving it a more rapid and predictable absorption and less inter and intra patient variability.

Topical delivery:

Topical administration of drugs can have advantages over other methods for several reasons, one of which is the avoidance of hepatic first pass metabolism of the drug and related toxicity effects.

The use of lecithin/IPP/waterNanoemulsion for the transdermal transport of indomethacin and diclofenac has also been reported which has increase the permiability of the human stratum corneum.

Ocular Delivery:

For the treatment of eye diseases, drugs are essentially delivered topically. O/W Nanoemulsions have been investigated for ocular administration, to dissolve poorly soluble drugs, to increase absorption and to attain prolong release profile.The Nanoemulsions containing pilocarpine were formulated using lecithin, propylene glycol and PEG 200 as co- surfactant and IPM as the oil phase.

Nanoemulsions in biotechnology:
Many enzymes, including lipases, esterases, dehydrogenases and oxidases often function in the cells in microenvironments that are hydrophobic in nature. In biological systems many enzymes operate at the interface between hydrophobic and hydrophilic domains and these usually interfaces are stabilized by polar lipids and other natural amphiphiles.
Enzymatic catalysis in Nanoemulsions has been used for a variety of reactions, such as synthesis of esters, peptides and sugar acetals transesterification; various hydrolysis reactions and steroid transformation. The most widely used class of enzymes in microemulsion-based reactions is of lipases.

7.3.8) USES:
Nanoemulsions could be and have been applied in various aspects of drug delivery including:
 Cosmetics and transdermal delivery of drug,
 Cancer therapy,
 Vaccine delivery,
 Prophylactic in bio-terrorism attack,
 Non-toxic disinfectant cleaner,
 Cell culture technology,
 Formulations for improved oral delivery of poorly soluble drug,
 Ocular and otic drug delivery,
 Intranasal drug delivery,
 Pulmonary delivery of drugs.

7.4 MULTIPLE EMULSIONS:
Novel development in emulsion technology. Complex type of multiple system.

7.4.1) TYPES OF MULTIPLE EMULSION:
Types of multiple emulsions –
1. w/o/w system – • Oil droplet surrounded by aqueous phase.
• In most cases, two aqueous phase are identical therefore a W1/O/W1 emulsion is a two component system. In some cases a W1/O/W2 is a three component system.
2. o/w/o system – • Water phase separates internal and external oil phase.
7.4.2) ADVANTAGES -
1. Protect active drug from degradation.
2. High encapsulation efficiency.
3. Prolonged or controlled drug release can be achieved.
4. Easy to produce and scale up. 5. Economical.
7.4.3) DISADVANTAGES -
1. Low thermodynamic stability.
2. It is bulkier system.
3. Disagreeable taste in some case.
7.4.4.) FORMULATION AND MANUFACTURE OF MULTIPLE EMULSION -
• Either by the re-emulsification of a primary emulsion or they can be produced when an emulsion inverts from one type to another.
1-Two step Emulsification(double Emulsification)
2-Micro channel emulsification process
3-Phase inversion technique (one step technique)
4-Membrane Emulsification technique

1.Micro Channel Emulsification Process
• Two type of channel:
 T– junction channel: -

2.Modified Double Emulsion Technique

3. Phase inversion.

4..Membrane                          Emulsification                                 Techniquez

7.4.5) MICROSCOPIC EXAMINATION
color ,consistancy ,Homogenicity. 2. Macroscopic examination – Average globule size & size distribution coarse multiple emulsion > 3micron fine multiple emulsion 1-3 micron micro multiple emulsion <1 micron

7.4.6) APPLICATIONS
• Controlled and Sustained Drug Delivery
• Drug Targeting
• Vaccine Adjuvant
• Cosmetics preparation
• Taste masking of the drug
• Haemoglobin Multiple emulsion as an oxygen Delivery system.

1.Multiple emulsion in controlled release drug delivary.
curcumin extract nanoencapsulated in chitosan and crosslinked with triployphosphate via multiple emulsion shows 96.28% encapsulation efficacy with controllled release.

2.Multiple emulsion in protein delivary Insulin delivary – EPA ,DHA, INSULIN multiple emulsion result shows DHA facilitate intestinal insulin absorption without inducing serious damage.

3.Others – a) For delivery of blood substitutes. b) For drug stability. c) In microencapsulation. d)Thermo reversible multiple emulsions. e) Food processing.

8.OTHER EMULSIONS

8.1 ORAL EMULSIONS
are oral liquids containing one or more active ingredients. They are stabilized oil-in-water dispersions, either or both phases of which may contain dissolved solids. Solids may also be suspended in oral emulsions. When issued for use, oral emulsions should be supplied in wide-mouthed bottles. Firstly prepared oral emulsion was cyclosporin.

8.2 PARENTERAL EMULSIONS
are special o/w emulsions used to feed patients whose medical condition makes them unable to eat normally. Therefore, parenteral emulsions must comply with several specifications. One is that the maximum droplet size must be below 5μm in order to avoid the risk of a pulmonary embolism.

8.3 RADIOPAQUE FLUOROCARBON (RFC) EMULSIONS
were prepared with small particle size and high concentration of the fluorocarbon. When RFC emulsions were injected intravenously in hamsters, rats, and mice with eight types of malignant tumors, the tumors became radiopaque and remained radiopaque for days to weeks after injection. Light and electron microscopy revealed characteristic fluorocarbon vacuoles primarily in the tumor macrophages. Thus RFC emulsions may be useful in detection of malignant tumors.

8.4 GEL EMULSIONS:
A series of novel and stable water in oil w/o gel-emulsions was created by utilizing a new cholesteryl derivative, a low-molecular mass gelling agent, as a stabilizer. The gel-emulsions could be prepared by simple agitation of the mixtures at room temperature, while heating, cooling, and addition of a co-solvent or other additional component are unnecessary. SEM and optical microscopy studies revealed the foam-like structures of the gel-emulsions. Porous polymer monoliths could be prepared by polymerizing gel-emulsions with organic monomers as a continuous phase.

9. PHARMACEUTICAL APPLICATIONS OF EMULSIONS:
Emulsion is used widely in pharmaceutical and cosmetic industries. Pharmaceutical applications are classified according to the route of administration i.e. topical, oral or parenteral. There are following major applications of emulsions in pharmacy.
Dermatological Creams and Lotions:
Creams and lotions are used topically to the affected area only. Nowadays instead of greasy and semisolids, water washable and non-staining products are being used which are more acceptable to patients.
Patient Acceptance and Compliance:
Water insoluble compounds are orally administered as o/w emulsion with pleasant taste e.g.
vitamin A, E, D and K are absorbed more quickly when emulsified.
Bioavailability:
Some therapeutic agents show bioavailability more when given in the form of emulsions e.g. Heparin and insulin.
Modern Drug Delivery Concept:
Non-absorbable macromolecules are absorbed to small extent when given orally as such insulin and heparin and they may even be digested in stomach. But when these agents are given in emulsified form they are not digested and are fully absorbed.
Intravenous Fat Emulsion:
The intravenous fat emulsions are used to supply or deliver isotonic liquids in small amount i.e. volume to provide large amount of energy to the body. The fat emulsions for intravenous nutrition
generally contain vegetable oil, a phospholipid and emulsifying agent. The examples are: Intralipid, Lipofundins and Lipofunduns

References:-
Remington, The science and practice of pharmacy,21st edition, chapter 20. o Bentley's Textbook of Pharmaceutics,1st edition,chapter 5
Ansel's Pharmaceutical Dosage Forms and Drug Delivery System,loyd
V.Allen,Jr,Howard C.Ansel,10th edition. o Theory and practice of industrial pharmacy, Leon Lachman, Herbert A. Lieberman, Joseph L. Kanig,3rd edition. o www.link.springer.com o www.wiley-vch.de o www.ncbi.nlm.nih.gov o www.particlescience.com o www.researchgate.net o www.pharmacopeia.cn
www.scribed.com
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