Methods of Preparation of Novel Emulsion

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Presented By

Manali Parab

M.Pharmacy Ist year (Sem Ist)

Pharmaceutics Department

Emulsion Emulsion can be defined as heterogeneous

system where one immiscible liquid is dispersed in another in the form of droplets and stabilized by third component called emulsifying agent

These have been described as heterogeneous systems of one immiscible liquid dispersed in another in the form of droplets, which usually have diameters greater than 1 μm .

Types of emulsion Oil in water (o/w) Water in oil (w/o)

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MULTIPLE EMULSION

MULTIPLE EMULSION Multiple emulsions are more complex systems as the drops of the

dispersed phase themselves contain even smaller dispersed droplets which normally consist of a liquid which is miscible, and in most cases, is identical with the continuous phase.

They are therefore, emulsions of emulsions. For each type of multiple emulsion, the internal and external phases are alike and an intermediate phase separates the two like phases.

The intermediate phase is immiscible with the two like phases. An emulsifier is present to stabilize the emulsion and a variety of ionic

and non-ionic surfactants are available for this purpose. Lipophilic (oil-soluble, low HLB) surfactants are used to stabilize W/O

emulsions, whereas hydrophilic (water-soluble, high HLB) surfactants are used to stabilize oil/water systems.

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The oil layer acts as a membrane separating these two aqueous phases.

Polar molecules dissolved in either the internal aqueous phase or the external continuous aqueous phase can pass through the oil layer by diffusion because of the concentration gradient.

In the case of water this is driven by osmotic pressure. Molecules are often transported via micelles of hydrophobic surfactant present in the oil phase. Water diffusion causes swelling, bursting, or shrinkage of the internal aqueous droplets, affecting the stability of the multiple droplets as well as the release profiles of the active ingredients loaded in the inner dispersed aqueous phase

For eg. Valsartan multiple emulsion

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Method of preparation

Two step emulsification

Phase inversion technique

Membrane emulsification

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Two step emulsification

Complex system

Liquid membrane system

Thermodynamically stable

Low HLB added to Oily phase

Low HLB: HydrophobicHigh HLB:

hydrophobic

Require two emulsifier

Multiple emulsion

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Multiple emulsion w/o/w contains two types of emulsifier

Low HLB surfactants ( hydrophobic in nature)

High HLB surfactants ( hydrophilic in nature)

Low HLB surfactants are used in dispersed phase

High HLB surfactants are used in continuous phase

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Two step emulsification

Phase inversion technique/ one step emulsification

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Oil +lipophilic surfactant aqueous solution +hydrophillic emulsifier

migration of the emulsifier between phases

concentration of dispersed globules in dispersion medium is quite high i.e., globules are packed

very closely in suspending fluid.

w/o/w emulsion

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Membrane emulsification technique In this method, a w/o emulsion (a

dispersed phase) is extruded into an external aqueous phase (continuous phase) with a constant pressure though a porous glass membrane.

The particle size can be controlled by controlling size of porous glass membrane.

Porous glass used is Shirasu porous glass given by SPG technology Miyazaki, Japan

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The relation between membrane pore size and particle size of emulsion exhibits good correlation as described by the

formula:Y= 5.03X + 0.19 Where, X= the pore sizeY= the mean particle size A micro porous glass membrane with narrow pore size

range was used successfully for preparing stable simple (o/w) and water-oil-water (w/o/w) type emulsion

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Cross-Flow Membrane Emulsification

To prepare monodisperse emulsion using a particular glass

membrane called Shirasu Porous Glass (SPG) membrane (SPG Technology, Miyazaki, Japan)

In cross-flow membrane emulsification, the dispersed phase is pressed through a microporous membrane (micropore diameter is dp) while the continuous phase flows along the membrane surface. Droplets grow at micropores and detach at a certain size (dd), which is determined by the balance between the forces acting on the droplet.

Emulsifiers in the continuous phase stabilize the newly formed inter-face, to prevent droplet coalescence immediately after formation.

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DISADVANTAGES

Direct membrane emulsification (DME). There are some

potential disadvantages

with this technique

(i) the relatively low maximum dispersed phase flux (typically

0.01–0.1m3/(m2h)) that leads to low productivity;

(ii) it is difficult to prepare uniform emulsion droplets when

the dispersed phase has high viscosity

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(iii) Uniform emulsion can only be prepared using a microporous membrane with very uniform pores. Because of these restricted conditions, there have been some limitations in choosing the dispersed phase, the continuous phase, and the membrane to obtain the desired emulsification products

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MARKETED PRODUCTS

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Microemulsion

Microemulsion

ultra low interfacial tension

Mixture ofSurfactants & cosurfactant

transparent or nearly

transparent

Microemulsion

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Three types of microemulsion are likely to be formed

O/W microemulsionW/O microemulsionBicontinuous microemulsion

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Microemulsion Vs Macroemulsion

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Microemulsion Vs Macroemulsion

Formulation Microemulsion formulation is specific to the nature

of oil/surfactant pair, surfactant concentration and the oil/surfactant ratio, the concentration and nature of co-surfactant and surfactant/co-surfactant ratio and the temperature.

Hence main components of microemulsion system are as follows

Oil phase Primary surfactant Secondary surfactant (co-surfactnt) Co-solvent

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MICRO EMULSIFICATION

Methods of formulation of microemulsion

Phase titration method (water titration method) Microemulsion are prepared by spontaneous

emulsification method (phase titration method) and can be depicted using phase diagrams.

Microemulsion formed with several association structures (emulsion, micelles, various gels and oily dispersions) depending on chemical composition and concentration of various substances

As quaternary phase diagram is difficult to interpret, pseudo ternary diagrams are constructed to find out different zones, in each corner of the diagram represents 100% of each component

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Ternary phase diagramsNumber of intermediate structural phases, including

bicontinuous, lamellar, hexagonal and multiple phases, when a mixture of surfactant and oil at certain ratios is mixed gradually with water.

Bicontinuous structure may exist in systems where the amount of water and oil are similar and both oil and water exist as a continuous phase

Multiple phases may exist where there is insufficient surfactant to form a single microemulsion phase, particularly for compositions close to the oil-water binary axis

The transitions between the various phases mapped out in the phase diagram can be driven by changing the temperature or addition of a component

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Preparation of samples for analysis and construction of phase diagrams1. One is titration of a mixture of two components

with the third component, for example, using water to titrate the mixture of surfactant and oil.

2. The other is preparation of a large number of samples with different compositions (i.e. different ratios of three components)

In order to speed up the process, heat and sonication are often employed in the experimentation

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TERNARY PHASE DIAGRAMS

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Emulsion titration/dilution method This method involves a two step process in which a premade nonionic

surfactant stabilized (e.g. Tween 80) o/w conventional emulsion is diluted into an aqueous surfactant micellar solution (e.g. 1% Tween 80)

This method can thus be called ‘emulsion titration or dilution method’, however, this method involves both high energy and low energy methods

Formation of microemulsions by the emulsion dilution method was shown to be highly dependent on the concentration of oil in the final mixture.

This means that the level of oil concentration required to be diluted into the surfactant solution to enable to form microemulsions (e.g., oil droplet size smaller than 50 or 100 microm) is limited and determined by the amount of titrated conventional emulsion into a surfactant solution

This method has also been called “oil exchange”, “swelling of o/w emulsion”, “oil solubilisation” or “molecular transport”

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It was shown that the size of oil droplets smaller than 100 nm could be formed by this approach only when a oil concentration added was lower than 1.5 wt% oil in the final mixture

When the volume of emulsion added has a relatively low concentration of oil droplets, all of the oil molecules in the emulsion move out of the droplets and are incorporated into the surfactant micelles.

several possible mechanisms (1) oil molecules are directly solubilized in water, and

then they are accommodated by micelles in the aqueous phase;

(2) oil molecules are incorporated into micelles due to the collision of micelles with the surface of emulsion droplets;

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DISADVANTAGES

Certain types of emulsifiers can be used which are limited to mostly nonionic small molecule surfactants

Certain types of low viscosity and non triglyceride oils, and the level of oil concentration should be low

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Nanoemulsion Nanoemulsion can be defined as oil in water emulsion

with mean droplets diameters ranging from 50 to 100nm. It is also called as sub micron emulsion or mini emulsion These are group of dispersed particles used for

pharmaceutical and biomedical aids and vehicles that show great promise for cosmetics, diagnosis, drug therapies and bio technologies.

Due to their small droplet size Nanoemulsions possesses stability against sedimentation or creaming with Ostwald forming main mechanism Nanoemulsions breakdown.

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Methods of formulation of nanoemulsion

High pressure homogenization In high pressure homogenizer, the dispersion of

two liquids (oily phase and aqueous phase) is achieved by forcing their mixture through small inlet orifice at very high pressure (500 to 20000psi), which sublet the product to intense turbulence and hydraulic shear resulting in extremely fine particles of emulsion.

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Aqueous phase+ oleaginous phase (heated and pH adjustment) heated and filtration 41

Add emulsifying agent

Rapid cooling

High pressure homogenizer (500 to 20000psi)

Formation of droplets of very small size

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High pressure homogenizer

Microfluidization Microfluidic technologies are indicated to manipulate

small quantities of liquids or fluids usually through channels with at least one dimension smaller than 1 mm, for emulsion formation, mixing and dispersion.

Microfluidizer high shear fluid processors are unique in their ability to achieve uniform particle size reduction, bottom-up crystallization and efficient cell disruption.

Product enters the system via the inlet reservoir and is powered by a high-pressure pump into the interaction chamber at speeds up to 400 m/s.

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An interaction chamber where two channels of fluid flow at high velocity and collide with each other

When the fluids from the two channels collide, it generates intense, disruptive forces that result in very small emulsion droplets.

It is then effectively cooled, if required, and collected in the output reservoir.

The exclusive fixed-geometry interaction chambers combines with a constant pressure pumping system to produce unparalleled results

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Microfluidizer

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Ultrasound emulsification In this method, a probe emits ultrasonic waves (20kHz)

to disintegrate microemulsion by means of cavitation forces.

In the dispersing zone, imploding cavitation bubbles cause intensive shock waves in the surrounding liquid and result in the formation of liquid jets of high liquid velocity.

n order to stabilize the newly formed droplets of the disperse phase against coalescence, emulsifiers (surface active substances, surfactants) and stabilizers are added to the emulsion. 

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As coalescence of the droplets after disruption influences the final droplet size distribution, efficiently stabilizing emulsifiers are used to maintain the final droplet size distribution at a level that is equal to the distribution immediately after the droplet disruption in the ultrasonic dispersing zone.

By varying ultrasound energy input and time, the nanoemulsion of desired properties can be obtained.

Undesirable for thermolabile drugs and macromolecues (retinoids, proteins, enzymes and nucleic acids)

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49Ultrasonic emulsification

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PROPOPOL INJECTION

By “troikaa”

Referencehttps://www.ncbi.nlm.nih.gov/pubmed/17076645http://www.slideshare.net/bharathpharmacist/multiple

-emulsionshttp://innovareacademics.in/journals/index.php/ijhs/article/view/219/167http://www.google.com/patents/US5322704http://sphinxsai.com/2013/janmar/pharmpdf/

PT=18(132-146)JM12.pdfhttp://jpharmsci.org/article/S0022-3549(15)32351-0/pdfhttp://mro.massey.ac.nz/bitstream/handle/

10179/5594/02_whole.pdf?sequence=2&isAllowed=y

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http://www.ijddr.in/drug-development/preparation-and-optimization-of-nanoemulsions-for-targeting-drugdelivery.php?aid=5740

http://www.slideshare.net/MUHEEM_007/nanoemulsion

Vesicular and Particulate Drug Delivery System by Prof. R.S.R. Murthy

Controlled and Novel Drug Delivery N.K. Jain CBS Publishers & Distributors

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THANK YOU

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