microemulsion by atul mangukiya

04/10/2023 1

MICROEMULSIONBASIC PRINCIPLES, FORMULATION &

EVALUATION

• Guided by:– Dr. Akshay koli– Assistant professor

• Prepared by:– Atul mangukiya– 201204100410028– M.Pharm.3rd sem

Pharmaceutics Department

uka tarsadia university

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CONTENT

• Introduction

• Basic principles (theories)

• Types of micro emulsion

• Formulation

• Evaluation

• References


INTRODUCTION

Surfactant

Oil Phase

Water Phase

Co-Surfactant

What is Micro Emulsion?


Microemulsion• Microemulsions are thermodynamically stable dispersions of oil and

water stabilized by a surfactant and, in many cases, also a

cosurfactant.

• Microemulsions can have characteristic properties such as ultralow

interfacial tension, large interfacial area and capacity to solubilize

both aqueous and oil-soluble compounds.

Theories of Microemulsion Formation1. Interfacial or mixed film theories.

2. Solubilization theories.

3. Thermodynamic treatments.


Interfacial/Mixed Film Theories:

• They considered that the spontaneous formation of microemulsion

droplets was due to the formation of a complex film at the oil-water

interface by the surfactant and co-surfactant.

• This caused a reduction in oil-water interfacial tension to very low values

(from close to zero to negative)

• equation. γ i = γo/w -πi

Where,

γ o/w = Oil-water interfacial tension without the film present

πi = Spreading pressure

γi =Interfacial tension


Mechanism of curvature of a duplex film:

• The interfacial film should be curved to form small droplets to explain

both the stability of the system and bending of the interface.

• A flat duplex film would be under stress because of the difference in

tension and spreading of pressure on either side of it.

• Reduction of this tension gradient by equalizing the two surface tensions

is the driving force for the film curvature.

• It is generally easier to expand the oil side of an interface than the water

side and hence W/O microemulsion can be formed easily than O/W

microemulsion.


Solubilization Theories:-

• Illustrated the relationship between reverse micelles and W/O

microemulsion with the help of phase diagrams.

• The inverse micelle region of ternary system i.e. water, pentanol and

sodium dodecyl sulphate (SDS) is composed of water solubilized reverse

micelles of SDS in pentanol.

• Addition of O-xylene up to 50% gives rise to transparent W/O region

containing a maximum of 28% water with 5 % pentanol and 6% surfactant

(i.e. microemulsions).

• These four component systems could be prepared by adding hydrocarbon

directly to the inverse micellar phase by titration.


Thermodynamic theory • The process of formation of oil droplets from a bulk oil phase is

accompanied by an increase in the interfacial area ∆A, and hence an

interfacial energy ∆G .

• The entropy of dispersion of the droplets is equal to T ∆ S and hence the

free energy of formation of the system is given by the expression.

∆Gf = γ ∆a - T ∆S

Where,

∆Gf = free energy of formation

∆A = change in interfacial area of microemulsion

∆ S = change in entropy of the system

T = temperature

γ = surface tension of oil water interphase


• When the interfacial tension is made sufficiently low that the interfacial

energy becomes comparable to or even lower than the entropy of

dispersion.

• The dominant favorable entropic contribution is very large dispersion

entropy arising from the mixing of one phase in the other in the form of

large number of small droplets.

• The free energy of formation of the system becomes zero or negative.

• This explains the thermodynamic stability of micro emulsions.

• The co-surfactant along with surfactant lower the interfacial tension to a

very small even transient negative value .


Main three components

1. Oil phase

2. Surfactant

3. Cosurfactant


Constituents of Microemulsion

Oil phase :-Isopropyl Myristate

Oleic acid Olive oil

Mineral oil Medium chain

triglyceride Soybean oil Captex 355

Isopropyl palmitate Sunflower OilSafflower Oil

Surfactants :- Tween 80 Tween 40

Labrafil M1944CSPolyoxyethylene-35-

ricinoleate Brij 58 Span 80

Cremophor EL Labrasol

Cremophor RH Lecithin

Cosurfactant/Stabilizer :-

Propylene glycolEthylene glycol

Ethanol1-butanol

Isopropyl alcohol PEG 600Glycerol

PEG 400


Oil Component

• As compare to long chain alkanes, short chain oil penetrate the tail group region to a greater extent and resulting in increased negative curvature (and reduced effective HLB).

• Following are the different oil are mainly used for the formulation of microemulsion:

1. Saturated fatty acid-lauric acid, myristic acid,capric acid

2. Unsaturated fatty acid-oleic acid, linoleic acid,linolenic acid

3. Fatty acid ester-ethyl or methyl esters of lauric, myristic and oleic acid.

• The main criterion for the selection of oil is that the drug should have high solubility in it.

• This will minimize the volume of the formulation to deliver the therapeutic dose of the drug in an encapsulated form.


Surfactants

• It is to lower the interfacial tension which will ultimately facilitates

dispersion process and provide a flexible around the droplets.

• Generally, low HLB (3-6) surfactants are suitable for w/o

microemulsion, whereas high HLB (8-18) are suitable for o/w

microemulsion.


Co surfactants

• They allow the interfacial film sufficient flexible to take up different

curvatures required to form microemulsion over a wide range of

composition.

1. Short to medium chain length alcohols (C3-C8) reduce the

interfacial tension and increase the fluidity of the interface.

2. Surfactant having HLB greater than 20 often require the presence of

cosurfactant to reduce their effective HLB to a value within the

range required for microemulsion formulation.


• a) by reducing the interfacial tension

• b) By increasing the flexibility and fluidity of the interface by positioning

itself between the surfactant tails which alters the solvent properties of both

the dispersed and continuous microemulsion phases;

• c) by lowering overall viscosity.

• d) by being often soluble in both organic and aqueous phases, co-

surfactants help solubilise poorlysoluble compounds (e.g., peptides, vitames


Types of micro emulsion

• O/W Microemulsion

• W/O Microemulsion

• Bi continuous Microemulsion

04/10/2023 uka tarsadia university

Phase Behaviour

• For four or more components

pseudo ternary phase diagrams are

used to study the phase behaviour.

• In this diagram a corner represent a

binary mixture of two components

such as water/drug, oil/drug or

surfactant/co-surfactant.

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• With high oil concentration surfactant forms reverse micelles capable of

solubilizing water molecules in their hydrophilic interior.

• Continued addition of water in this system may result in the formation of

W/O micro emulsion in which water exists as droplets surrounded and

stabilized by interfacial layer of the surfactant / co-surfactant mixture.

• Finally, as amount of water increases, this lamellar structure will break

down and water will form a continuous phase containing droplets of oil

stabilized by a surfactant / co-surfactant (O/W microemulsions)


Preparation of Microemulsion

• Following are the different methods are used for the

preparation of microemulsion:

1. Phase titration method

2. Phase inversion 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 all components at once. In some systems, the order of

ingredient addition may determine whether a microemulsion forms or not.

•e.g.(w/o)

soybean oil, ethoxylated mono- and di-glycerides as surfactants and a

mixture of sucrose and ethanol as the aqueous phase.

Transparent microemulsions resulted from dilution of the oil-surfactant

mixtures with water along several regions in the pseudo-ternary phase

diagram.

Phase titration method


Phase inversion method :

Phase Inversion Temperature (PIT), i.e., the temperature range in which an o/w microemulsion inverts to a w/o type or vice versa.

• using non-ionic surfactants, polyoxyethylene are very susceptible to temperature since surfactant solubility (in oil or water) strongly depends on temperature.

With increasing temperature, the polyoxyethylene group becomes dehydrated, altering the critical packing parameter which results in phase inversion.

• For ionic surfactants, increasing temperatures increase the electrostatic repulsion between the surfactant headgroups thus causing reversal of film curvature.

Hence the effect of temperature is opposite to the effect seen with non-ionic surfactants.

Parameters Studied Techniques Used

Phase Behaviour Phase contrast microscopy and freeze fracture TEM

Size and Shape Transmission Electron Microscopy (TEM), SEM,DLS

Rheology Brookfield Viscometer

Conductivity Conductivity Meter

Zeta Potential Zetasizer

pH pH Meter

Drug Release Studies

Franz Diffusion Cells

Physical Stability Study

Ultracentrifuge

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EVALUATION


In Vitro Drug Permeation Studies • Determination of permeability coefficient and flux

– Excised human cadaver skin from the abdomen can be obtained

from dead who have undergone postmortem not more than 5

days ago in the hospital. The skin is stored at 4C and the

epidermis separated.

– The skin is first immersed in purified water at 60C for 2 min and

the epidermis then peeled off.

– Dried skin samples can be kept at -20C for later use.

– Alternatively the full thickness dorsal skin of male hairless mice

may be used.

– The skin shall be excised, washed with normal saline and used.


– The passive permeability of lipophilic drug through the skin is investigated using Franz diffusion cells with known effective diffusional area.

– The hydrated skin samples are used. The receiver compartment may contain a complexing agent like cyclodextrin in the receiver phase, which shall increase the solubility and allows the maintenance of sink conditions in the experiments.

– Samples are withdrawn at regular interval and analyzed for amount of drug released.

Fig. Franz diffusion cell


• Stability Studies– The physical stability of the microemulsion must be determined

under different storage conditions (4, 25 and 40 °C) during 12

months.

– Depending on different regulatory agency requirement it’ll vary

according to them.

– Effect of surfactant and their concentration on size of droplet is

also be studied.

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References:• Berry, natasha, "development and stability of microemulsions as carriers

for nutraceuticals" (2011). Theses and dissertations. Paper 679.• P. J. Sinko, Martin’s Physical Pharmacy & Pharmaceutical Science, 5th Ed.,

Wolters Kluwer Press, 2009, Chapter 16.• Lachman , the theory and practice of industrial pharmacy, 3rd ed.,Varghese

publishing house, 2008, chapter 17.• The science and practice of pharmacy 21st edition vol-1 remington 2005

pg.No.-315,316,763 published by wolters kluwer health(india) pvt.Ltd., New delhi.

• Microemulsion-based media as novel drug delivery systems www.Elsevier.Com/ locate / drugdeliv advanced drug delivery reviews 45 (2000) 89–121

• “Emerging trend of microemulsion in formulation and research” international bulletin of drug research., 1(1): 54-83 54

• Michael e aulton, “the design and manufacture of medicines”, elsevier publisher,third edition(2007)

uka tarsadia university

microemulsion by atul mangukiya

Technology

oilwater interfacial

oil droplets

oil component

oilwater interface

selection of oil

different oil

uka tarsadia university

interfacial film