Topical drug delivery system is the dosage form which is administered on the skin and other routes of drug delivery get failed or for skin disorders. The topical drug delivery system has the advantage of negotiating the first pass metabolism. It also helps to avoid the risk and inconvenience of i.v route therapy. Topical formulations are prepared in different consistency such as solid, semisolid, and liquid. The topical delivery system is failed in the administration of hydrophobic drug. In each formulation with the active ingredients many excipients are used. Sometimes more than one formulation can be combined to enhance the drug delivery; emulgel is such type of combination. It is the combination of emulsion and gel. Emulgel is prepared both in oil- in- water and water- in- oil type emulsion mixed with gel. Oil- in- water type is used for lipophilic drugs and water- in- oil type is used for hydrophobic drugs' delivery Emulgel have many advantages like thixotropic, greaseless, easily spreadable, easily removable, emollient, non-staining, bio-friendly, pleasing appearance, transparent and cosmetically acceptable, which also have a good skin The emulsion and gel preparations have their own properties. But the gels show some limitations as hydrophobic drug delivery. This limitation is overcoming by emulgel. By the use of gelling agent classical emulsion can be converted in to emulgel.

       
           
       
Fig.1 Emulgel Structure

Two types of topical delivery products are available. They are external and internal products. As their name indicates, the external products are applied by spreadingor spraying, and the internal products are applied orally, vaginally or rectally. The topical preparation can be classified by their consistencies, which are solid preparation, liquid preparation, semi-solid preparation and miscellaneous preparation. factors will affect the absorption of drug through every route. Some factors like skin thickness, skin pH, hydration, inflammation, partition coefficient, molecular weight and other factors affect topical route.

The topical delivery system has many advantages and also disadvantages. The main advantage is avoidance of first pass metabolism and gastrointestinal incompatibility. Nearly all topical preparations are applied on the skin. They penetrate through the skin and give the action in right site.

The skin is the largest sense organ in our body, which consist of approximately 2 m2 of surface area and pH of skin is 4.0 to 5.6. The skin contains four layers; non- viable epidermis, viable epidermis, viable dermis and subcutaneous connective tissue.

Non- viable epidermis [stratum corneum]: It is the outer layer of skin, which is 10-20 cell thick. The cells are 34-44 µm long, 25-36 µm wide, 0.5- 0.20 µmthick with surface area of 750-1200 µm.

Viable epidermis thickness. It lies between stratum corneum and dermis with 1050 µm

The tonofibrils help for joining the cells.

Dermis: It is seen under the viable epidermis, and it is a structural fibrin. Thickness of the dermis ranges from 2000-3000 µm and contains loose connective tissue.

Mechanism of Skin Penetration

Skin penetration enhancers are the molecules which reversible to remove the barrier resistance of the stratum corneum. They allow drugs to penetrate more readily to the viable tissues and hence enter the systemic circulation.

The intercellular routes accelerants may interact at the polar head groups of the lipids, within aqueous region between lipid head group and between the hydrophobic tails of the barrier.

The common mechanism is to protect the body for unwanted particles from the environment. The main barrier of the skin is located in the outermost layer of skin that is epidermis.

Since the lipid regions in the stratum corneum forms the only continuous structure, substance applied on to the skin always have to pass these region.

The major obstacle for topical drug delivery is the low diffusion rate of drug across the stratum corneum. Several methods have been assessed to increase the permeation rate of drugs temporarily.

Defination:

Emulgel is oil in water or water in oil emulsion carrying drug to be incorporated in gel base to obtain gellified emulsion. Emulgel shows the controlled and better release effect of drug by virtue of combined effect of gel and emulsion with increased stability.Normally the emulgels are used as anti-inflammatory drugs. In the coming years, topical drugs delivery will be used extensively to impart better patient compliance.

Examples of Emulgel: Miconz-H-emulgel, Isofen emulgel, Diclon emulgel,etc.

ADVANTAGES

• Incorporation of hydrophobic drugs

• Better loading capacity

• Better stability

• Controlled release

• No intensive sonication

• Avoiding first pass metabolism

• Avoiding gastrointestinal incompatibility

• More selective for a specific site

• Improved patient compliance

• Convenient and easy to apply

• Improve bioavailability and even the low doses can be effective in comparison with other conventional semi solid preparation.

DISADVANTAGES

• Skin irritation on contact dermatitis

• The possibility of allergenic reactions

• The poor permeability of some drugs through the skin

• Drugs of large particle size are not easy to absorb through the skin

• The occurrence of the bubble during formulation of emulgel

Can be used only for drugs which require very small plasma concentration for action. 6.

Enzyme in epidermis may denature the drugs

Emulsions are of different types depending on the size of droplets or nature of distribution

1) Macroemulsion gel

2) Nanoemulsion gel

3) Microemulsion gel

1) Macroemulsions gel

These are most common type of emulgels where the particle size of droplets of emulsion is more than 400nm. They are visually opaque but the individual droplets can be easily observed under microscope. Macroemulsion are thermodynamically unstable, but can be stabilized using surface active agents. E.g. Khullar R. et al, mefenamic acid emulgel was prepared using Carbopol 940 as gelling agent. Liquid paraffin was used as oil phase. Mentha oil and clove oil was used as penetration enhancer. Then it was evaluated for rheological studies, spreading coefficient studies, skin irritation test, in-vitro release, etc.

2) Nanoemulsion gel

When nanoemulsion is incorporated into gel it is called as nanoemulgel. Nanoemulsion are thermodynamically stable transparent (translucent) dispersions of oil and water stabilized by an interfacial film of surfactant and co surfactant molecules having a droplet size of less than 100nm. Nanoemulsion formulations possess improved Transdermal and dermal delivery properties in vitro as well as in vivo. This has improved transdermal permeation of many drugs over the conventional topical formulations such as emulsions and gels.

E.g. Singh B. P et al, prepared Carvedilol nanoemulgel using oleic acid and isopropyl myristate (3:1) as oil phase. Tween 20 and Carvedilol were used as surfactant and co surfactant respectively. Carbopol 934 was used as gelling agent.

3)Microemulsion gel:

Microemulsions are transparent and thermodynamically stable as their droplet size range from 10 to 100nm and they do not coalesce. Microemulsions are composed of oil, co-surfactant, and water in specific proportions.

The ingredients of Microemulsion could facilitate the permeation rate of the drug by reducing the diffusion barrier of the stratum corneum. However, due to low viscosity of Microemulsion, their less retention capacity in the skin restrains its application in the pharmaceutical industry To overcome this disadvantage, gelling agents such as

Carbopol 940, xanthan gum and carrageenan have been added into the Microemulsion for forming Microemulsion based gel in order to increase its viscosity which could be suitable for topical application.

Moreover, Microemulsion based gel prevents the absorption of drug in the blood stream and provide higher drug accumulation in the skin for efficient action.

E.g. Bachhav Y. G et al, prepared clotrimazole Microemulsion based vaginal using Carbapol 90 as oil phase and Cremophor EL as surfactant. Carbopol ETD 2020 is used as gelling agent.

FORMULATION OF EMULGEL

For the preparation of emulgel some constituents are used including drug, which are:

1. Vehicle

Properties of vehicles is that

Deliver the drug to target site.

Sustain a therapeutic drug level in the target tissue for a sufficient duration to

provide a pharmacological effect.

Release the drug so it can migrate freely to the site of action.

a) Aqueous material

This forms the aqueous phase of the emulsion. Commonly used agents e.g. water, alcohols.

b) Oils

These agents from the oily phase. For externally applied emulsions, mineral oils, either alone or combined with soft or hard paraffin's are widely used. In oral preparations nonbiodegradable mineral and castor oils that provide a local laxative effect and fish liver oils or various fixed oils of vegetable origin (e.g.: arachis, cottonseed, and maize oils) as nutritional supplements.

Gelling agents

These are used to increase consistency of dosage form and provide gelled behavior. Gelling agent are of 2 types natural and synthetic. Incorporation of gelling agent to a system makes it thixotropic. It is observed that there exist an inverse relationship between concentration of gelling agent and extent of drug released. Then get hydrated and swell. Besides its hydrophilic nature, its cross-linked structure and its insolubility in water makes carbopol a potential candidate for use in controlled release drug delivery system. HPMC emulgel shows better drug release than carbopol. Ex: carbopol-934(1%), HPMC-2910(2.5%).

Penetration enhancers

These are agents that partition into and interact with skin constituents to induce a temporary and reversible increase in skin permeability. E.g: Oleic acid, lecithin, isopropyl myristate, urea, eucalyptus oil, chenopodium oil, pyrrolidone, laurocapran, dimethyl sulphoxide, linoelic acid, menthol.

Properties of penetration enhancer

• They should be non-toxic, non-irritating and non-allergenic.
• They would ideally work rapidly and the activity and duration of effect should be both predictable and reproducible.
• They should have no pharmacological activity within the body i.e. should not bind to receptor sites.
• The penetration enhancers should work unidirectional i.e. should allow therapeutic agents into the body while preventing the loss of endogenous material from the body.
• The penetration enhancers should be appropriate for formulation into diverse topical preparations, thus should be compatable with both excipients and drugs.
• They should be cosmetically suitable with an appropriate skin 'feel'.

Mechanism of penetration enhancer Penetration enhancers may act by one or more of three main mechanisms

1. Disruption of the highly ordered structure of stratum corneum lipid.

2. Interaction with intercellular protein.

3. Improved partition of the drug, co-enhancer or solvent into the stratum corneum.

4. Most of the hydrophobic drugs cannot be incorporated directly into gel base because solubility act as a barrier and problem arises during the release of the drug.

5. Emulgel helps in the incorporation of hydrophobic drugs into the oil phase and then oily globules are dispersed in aqueous phase resulting in o/w emulsion and this emulsion can be mixed into gel base. This may be proving better stability and release of drug than simply incorporating drugs into gel base.

• IDEAL PROPERTIES OF ADDITIVES
• They should be nontoxic.
• They should be easily available.
• They should be cheap.
• They do not be contraindicated.
• They should chemically and physically be stable.

PREPARATION OF EMULGEL

Emulgel are prepared by incorporating gel and emulsion. The emulsion and gel are prepared separately and mixed together. with gentle stirring. The chemicals are used as oil phase are castor oil, clove oil, iquid paraffin, etc. For preparing emulsion, aqueous phase and oil phase are taken separately and mixed together.

Then the gel is prepared by using gelling agent. After preparing gel and emulsion, they are mixed Water and alcohol are used as aqueous phase.

METHOD OF FORMULATION OF EMULGEL