Overview Of Pharmaceutical Emulsion

An emulsion may be defined as 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.

Emulsion

Either the dispersed phase or the continuous phase may vary in consistency from that of a mobile liquid to semisolid. 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.

Emulsifiers

An emulsifier (also known as an "emulgent") is a substance that stabilizes an emulsion by increasing its kinetic stability or by forming a thin film around the globules of dispersed phase. Emulsifiers are part of a broader group of compounds known as surfactants, or "surface active agents".

Surfactants (emulsifiers) are compounds that are typically amphiphilic, meaning they have a polar or hydrophilic (i.e. water-soluble) part and a non-polar (i.e. hydrophobic or lipophilic) part. Because of this, emulsifiers tend to have more or less solubility either in water or in oil. Emulsifiers that are more soluble in water (and conversely, less soluble in oil) will generally form oil-in-water emulsions, while emulsifiers that are more soluble in oil will form water-in-oil emulsions.

Classification Of Emulsifier

Emulsifying agents can be divided into 3 groups

1. Surfactants (Surface active agents)

2. Hydrocolloids

3. Finely divided solids

Mechanisms Of Emulsification

A number of different chemical and physical processes and mechanisms can be involved in the process of emulsification:

Surface Tension Theory

According to this theory, emulsification takes place by reduction of interfacial tension between two phases

Repulsion Theory

The emulsifying agent creates a film over one phase that forms globules, which repel each other. This repulsive force causes them to remain suspended in the dispersion medium

Viscosity Modification

Emulgents like acacia and tragacanth, which are hydrocolloids, as well as PEG (or polyethylene glycol), glycerine, and other polymers like CMC (carboxymethyl cellulose), all increase the viscosity of the medium, which helps create and maintain the suspension of globules of dispersed phase.

Action Of Emulsifier

1. reducing the interfacial tension between the phases

2. forming a barrier between the phases

3. promoting the formation of an emulsion

4. making it easier to prepare

5. producing finer droplet size

6. aiding stability to the dispersed state

Classification Of Emulsion

A. Emulsions can also be classified based on the mode of administration into:

1. Oral emulsions e.g., castor oil, liquid paraffin

2. External emulsions e.g., creams

3. Parenteral emulsions e.g., vitamins

4. Rectal emulsions e.g., enema.

B. Emulsions typically consist of a polar (e.g., aqueous) and a relatively nonpolar (e.g., an oil) liquid phase. Based on the nature of the internal and/external phase, emulsions can be classified into different types:

1. Oil In Water Emulsion

When the oil phase is dispersed as globules throughout an aqueous continuous phase, the system is referred to as an oil-in-water (o/w) emulsion. An o/w emulsion is generally formed if the aqueous phase constitutes more than 45% of the total weight and a hydrophilic emulsifier, such as sodium lauryl sulfate, triethanolamine stearate, sodium oleate, and glyceryl monostearate is used. The emulsifier is present in the external, continuous phase and helps stabilize the interface with the dispersed phase globules.

Read Also: Classification of oral dosage form

They are non greasy and are easily removable from the skin surface and 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 gives a positive conductivity test as water, the external phase is a good conductor of electricity.

2. Water In Oil Emulsion

When the aqueous phase is dispersed, and the oil phase is the continuous phase, the emulsion is termed as water-in-oil (w/o) emulsion. A lipophilic emulsifier is used for preparing w/o emulsions. The w/o emulsions are used mainly for external applications and may contain one or several of the following emulsifiers: calcium palmitate, sorbitan esters (Spans), cholesterol, and wool fats. Thus, the use of a lipophilic emulsifier enables the formation of w/o emulsions with the oil phase as the external, continuous phase.

Water-in-oil emulsions will have an occlusive effect by hydrating the stratum corneum and inhibiting evaporation of eccrine secretions. It has an effect on the absorption of drugs from W/O emulsions.

W/O emulsion is also useful for cleansing the skin of oil soluble dirt, although its greasy texture is not always cosmetically acceptable. 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 test, because oil is the external phase which is a poor conductor of electricity.

C. Depending upon the need, more complex systems referred to as “double emulsions” or “multiple emulsions” can be made. These emulsions have an emulsion as the dispersed phase in a continuous phase:

Multiple Emulsions

Multiple emulsions are emulsions whose dispersed phase contains droplets of another emulsion. Both water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) multiple emulsions are of interest as delayed- and/or sustained-action drug delivery systems. They also have applications in cosmetics. Emulsifying a w/o emulsion using water-soluble surfactants (which stabilize an oily dispersed phase) can produce w/o/w emulsions with an external aqueous phase, which generally has a lower viscosity than the primary w/o emulsion. Multiple emulsions can also be used for the encapsulation of peptides/proteins and hydrophilic drugs.

They can be considered as emulsions of emulsions, and have been shown to be secured in cosmetic pharmaceutical and separation sciences. Their pharmaceutical applications include taste masking, adjuvant vaccines, an immobilization of enzymes and sorbent reservoir of overdose treatments, and sometimes for the augmentation of external skin or dermal absorption. Prolonged release can also be obtained by means of multiple emulsions. These systems have some advantages, such as the protection of the ensnared substances and the possibilities of incorporating several active ingredients in the different compartments. Regardless of their importance, multiple emulsions have limitations because of thermodynamic instability and their complex structure.

D. By considering particle size, pharmaceutical emulsions can be:

1. Macroemulsions (droplets size usually exceeds 10 mm)

2. Miniemulsions (droplets size usually 0.1–10 µm)

3. Fine emulsion have a milky appearance and the globules size range from 0.25 to 25 µm (micrometre)

4. Microemulsions (droplets size usually 100-600 nm)

5. Nanoemulsions (droplets size usually below 100 nm)

In this post we shall discuss only microemulsion as it is more relevant.

Microemulsions

Microemulsions are visually homogeneous, transparent/isotropic systems of low viscosity. In their simplest form, microemulsions are small droplets (diameter 5–140 nm) of one liquid dispersed throughout another by virtue of the presence of a fairly large amount of surfactant(s) and cosolvent(s). Microemulsions have a very finely subdivided dispersed phase, and often contain a high concentration of the emulsifier(s) and a cosolvent (such as ethanol).

Microemulsions are thermodynamically stable for prolonged periods of time. They can be dispersions of o/w or w/o. The type of microemulsion (w/o or o/w) formed is determined largely by the nature of the surfactants.

For preparation of O/W microemulsion, we start with w/o emulsion using a low hydrophyliclipophylic balance (HLB) number surfactant .To this emulsion, an aqueous solution of high HLB number surfactant is added while stirring at a certain amount of addition, a ‛gel’ phase is produced and further addition of surfactant solution, an inversion into O/W emulsion take place.

For W/O microemulsion, one starts with O/W emulsion stabilized with an ionic or nonionic surfactant. This emulsion is titrated with a co-surfactant and the emulsion passes through a gel phase, after which further addition of co-surfactant results in the production of W/O microemulsion.

Microemulsions can be used to increase the bioavailability of poorly water-soluble drugs by incorporating them into the oily phase. Incorporation of etoposide and methotrexate diester derivative into w/o microemulsion has been suggested as a potential carrier for cancer therapy. However, a drawback of microemulsion is the possibility of disruption of the crystalline structure of stratum corneum. These lead to facilitated transdermal transport and skin irritation.

E. Structure of the system

1) O/W and W/O microemulsions: These usually have a size range of 0.1–5 μm with an average of 1–2 μm

2) Nanoemulsions: these usually have a size range of 20–100 nm. Similar to microemulsions, they are only kinetically stable

3) Micellar emulsions or microemulsions: these usually have the size range of 5–50 nm. They are thermodynamically stable

4) Double and multiple emulsions: these are emulsions-of-emulsions, W/O/W, and O/W/O systems

5) Mixed emulsions: these are systems consisting of two different dispersed droplets that do not mix in a continuous medium

Note that there.may be some more variation to the figure from different writers.

Tests For Identification Of Emulsion Types

• Dilution test: emulsion can be diluted only with external phase

• Dye test: water or oil soluble dyes

• CoCl2/filter paper test: filter paper impregnated with CoCl2 and dried (blue) changes to pink when o/w emulsion is added

• Fluorescence: some oils fluoresce under UV light

• Conductivity: for ionic o/w emulsions (o/w emulsions conduct electric current)

General Method Of Preparing Emulsion

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.

Phase Inversion Method

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

Continental And 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. Continental and dry gum methods differ in the proportion of constituents.

Wet Gum Method

In this method, the proportion of the constituents is the 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.

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 directly 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.

Breakdown Processes In Emulsion (Instability)

Emulsion stability refers to the ability of an emulsion to resist change in its properties over time. There are four types of instability in emulsions: flocculation, creaming/sedimentation, coalescence, and Ostwald ripening. And there are two other processes of breakdown of emulsion: phase inversion and breaking.

1. Flocculation

Flocculation occurs when there is an attractive force between the droplets, so they form flocs, like bunches of grapes. This process refers to aggregation of the droplets (without any change in primary droplet size) into larger units. It is the result of the van der Waals attraction that is universal with all dispersed systems. Flocculation occurs when there is not sufficient repulsion to keep the droplets apart to distances where the van der Waals attraction is weak. Flocculation may be ‘‘strong’’ or ‘‘weak,’’ depending on the magnitude of the attractive energy involved. This process can be desired, if controlled to its extent, to tune physical properties of emulsions such as their flow behaviour. It is redispersible upon shaking. It is a reversible process in which the droplets remain intact. Flocculation is considered as the precursor of coalescence.

2. Coalescence

Coalescence occurs when droplets bump into each other and combine to form a larger droplet, so the average droplet size increases over time. This refers to the process of thinning and disruption of the liquid film between the droplets with the result of fusion of two or more droplets into larger ones. The limiting case for coalescence is the complete separation of the emulsion into two distinct liquid phases. The driving force for coalescence is the surface or film fluctuations which results in close approach of the droplets whereby the van der Waals forces are strong thus preventing their separation.

3. a. Creaming

Emulsions can also undergo creaming, where the droplets rise to the top of the emulsion under the influence of buoyancy, or under the influence of the centripetal force induced when a centrifuge is used. 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 and does not change the droplet size so that it can be redispersed on shaking. Creaming can be minimized if the viscosity of the continuous phase is increase

3. b. Sedimentation

Sedimentation is the opposite phenomenon of creaming and normally observed in water-in-oil emulsions. Sedimentation happens when the dispersed phase is denser than the continuous phase and the gravitational forces pull the denser globules towards the bottom of the emulsion. Similar to creaming, sedimentation follows Stokes' law.

4. Ostwald Ripening (Disproportionation)

This results from the finite solubility of the liquid phases. Liquids that are referred to as being immiscible often have mutual solubilities that are not negligible. With emulsions, which are usually polydisperse, the smaller droplets will have larger solubility when compared with the larger ones (due to curvature effects). With time, the smaller droplets disappear and their molecules diffuse to the bulk and become deposited on the larger droplets. With time, the droplet size distribution shifts to larger values.

Phase Inversion

This refers to the process whereby there will be an exchange between the dispersed phase and the medium. For example, an O/W emulsion may with time or change of conditions invert to a W/O emulsion. In many cases, phase inversion passes through a transition state whereby multiple emulsions are produced.

Breaking

Complete separation of aqueous and oil phases. This is irreversible.