SPECIALIZED SPECIALIZED PHARMACEUTICAL PHARMACEUTICAL EMULSIONEMULSION

By

MARIA HANIF

(Mphil Pharmaceutics)

(2014-2016)

INTRODUCTION

An emulsion is thermodynamically unstable system in which one phase is uniformally distributed as globules in other phase and is stabilized by the addition of emulsifying agents.

The emulsions can be divided up into:1. Oil in water (O/W) emulsions and2. Water in Oil (W/O) emulsions.

1. O/W Emulsion:By dispersion of oil into water the oil drops

are the inner, dispersed phase. Water is the outer, continuous phase.

2. W/O Emulsion:By dispersion of water into oil the

water drops are theInner, dispersed phase. Oil is the outer,

continuous phase.Oil phase

Aq phase

Oil phase

Methods of Preparation of Emulsions

1) Continental or Dry Gum Method:1) Continental or Dry Gum Method:

"4:2:1" Method

4 parts (volumes) of oil

2 parts of water

1 part of gumDry gum method is used to prepare

the initial or primary emulsion from oil, water, and a hydrocolloid or "gum" type emulsifier.

2) Bottle or Forbes Bottle Method:

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

powdered acacia

+ Dry bottle

2 parts of oil

This method is not suitable for viscous oils (i.e. high viscosity oil).

3) English or wet Gum Method:

4 parts (volumes) of oil

2 parts of water

1 part of gum

4) Auxiliary 4) Auxiliary method

An emulsion prepared by other methods can also be improved by passing it through a hand homogenizer, which forces the emulsion through a very small orifice, reducing the dispersed droplet size to about 5 microns or less.

In situ soap methodIn situ soap method

wCalcium Soap : w/o emulsions contain oils such as

oleic acid , in combination with lime water ( calcium hydroxide solution, USP).

Prepared by mixing equal volumes of oil and lime water.

/o emulsions contain oils such as

Stability Issues:Emulsions are, by nature, physically

unstable; that is, they tend to separate into two distinct phases or layers over time.

Creaming occurs when dispersed oil droplets merge and rise to the top of an o/w emulsion or settle to the bottom in w/o emulsions. In both cases, the emulsion can be easily redispersed by shaking.

Coalescence (breaking or cracking) is the complete and irreversible separation and fusion of the dispersed phase.

Phase inversion or a change from w/o to o/w (or vice versa) may occur.

Emulsion Type and Means of Detection:

1) Dilution Test:

- o/w emulsion can be diluted with water.

- w/o emulsion can be diluted with oil.

2) Conductivity Test:

Continuous phase water > Continuous phase oil.

3) Dye-Solubility Test:

- water soluble dye will dissolve in the aqueous phase.

- oil soluble dye will dissolve in the oil phase.

4)Cobalt Chloride test:

Cobalt Chloride solution is used for identification of Emulsion. It is water soluble so it changes colour when encountered by O/W emulsion.

5:Fluorescence test:

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

MULTIPLE EMULSIONS:Multiple emulsion are complex system

which consist of both w/o and o/w at the same time.

There are potential matrices for the encapsulation of biactive compounds and for the controlled release compounds

w/o/w multiple emulsion are system where small water droplets are entrapped within larger oil droplets and they are disperse continuous water phase.

Because of presence of reservoir phase that can be use to prolong release of active ingredients.

This is made possible by double emulsification hence the systems are also called as “Double emulsions”.

These are also called as “Liquid membrane systems” as the liquid film which separates the liquid phases acts as a thin semipermeable film through which solute must diffuse in order to transverse from one phase to another.

Multiple emulsions are thermodynamically unstable.

They are often stabilized by using a combination of hydrophilic & hydrophobic surfactants.

The ratio of these surfactants is important in achieving stable multiple emulsions.

TYPES:

With optical microscopy method, multiple emulsions are classified as,

1. coarse (>3 micrometer in diameter) 2. Fine (1-3 micrometer in

diameter) 3. Micro-multiple emulsions (<1 micrometer in diameter)

W/O/W Type of emulsionW/O/W Type of emulsion

O/W/O type of emulsionO/W/O type of emulsion

Multiple emulsions can also be formulated by using either Multiple emulsions can also be formulated by using either oo11/o/o22/o/o11 systems or o systems or o11/o/o22/w formulations are possible. /w formulations are possible.

Examples of both are shown in FigureExamples of both are shown in Figure

Multiple emulsion w/o/w contain two emulsifiers:

1 Low HLB surfactant (Hydrophobic in nature)

2 High HLB surfactant (Hydrophilic in nature)

Low HLB surfactant use in disperse phase

High HLB surfactant use in continuous phase.

EMULSIFYING AGENTS

Emulsifier or surface active agent [SAA] is molecule which has two parts, one is hydrophilic and the other is hydrophobic. Upon the addition of SAA, it tends to form monolayer film at the oil/ water interface.

SURFACTANTS

Anionic Sodium oleate Pottasium oleateGlyceryl monostearate

Cationic Benzalkonium chloride

Non ionicspan 80span20Tween 20Tween 60Tween 80

Mechanism of release of drug:

1. Primary interface lying between the inner w/o phase contains the low

HLB surfactant. 2.Secondary interface lying between

droplets and continuous aqueous phase. Low and high HLB surfactant present in it. When hydrophilic surfactant in the continuous aqueous phase exceed its critical micelle concentration the resultant micelles may solubilize the hydrophobic surfactant present in oil phase.

METHOD OF PREPARATION

1) Solvent evaporation method

2) Two step emulsification.

3) Phase inversion technique.

SOLVENT EVAPORATION TECHNIQUE

TWO STEP EMULSIFICATION/ DOUBLE EMULSIFICATION

APPLICATONS

Multiple emulsions finds wide range

of applications in controlled or

sustained drug delivery, targeted

delivery, taste masking,

bioavailability enhancement, enzyme

immobilization, etc.

It will be able to provide a novel

carrier system for drugs, cosmetics

and pharmaceutical agents.

1. Hemoglobin multiple emulsion having specified properties is suitable for provision of oxygen as a blood substitute and other oxygen transfer processes.

2. W/O/W multiple emulsions are systems of potential interest in the oral administration of insulin. Although it has been shown that a single oral administration of insulin-loaded W/O/W multiple emulsion to diabetic rats led to the significant decrease of blood glucose.

3. (w/o/w) multiple emulsions and polymeric nanoparticle formulations containing influenza virus surface antigen hemagglutinin (HA) are thought to be suitable carriers for a vaccine delivery system.

4. Using a water-in-oil-in-water multiple emulsion system developed for pulmonary drug targeting, the effectiveness of tetrandrine as an antifibrotic agent.

5. To develop a prolonged and sustained release preparation , an albumin micro-sphere-in-oil-in-water emulsion was prepared. Tegafur was used as a model drug.

6. Vitamin c has been widely used in formulations of skin care products.

7. Multiple emulsions are also used in topical application ex… a w/o/w emulsion of Metronidazole.

REFERENCESREFERENCES1) Pharmaceutical Emulsions and Suspensions, edited by Francoise

Nielloud Gilberte Marti-Mestres.

2) Pharmaceutical Dosage Forms: Disperse systems, vol.3, second edition, Edited by Herbert A.Liberman, Martin M. Rieger and Gilbert S. Banker.

3) some studies on Multiple Emulsions by G.Vishwanadham, (Ph.D thesis, KU)

4) Advances in Controlled and Novel Drug Delivery Systems, Edited by N.K. Jain.

5) Targeted and controlled Drug Delivery Novel Carrier Systems

by -S.P. Vyas and R.K. Khar. http://www.aapsj.org/view.asp http://www.blackwell-synergy.com http://www.rsc.org/delivery/_ArticleLinking http://cat.inist.fr http://iufost.edpsciences.org