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922
Review Article
Wagh et al. WORLD JOURNAL OF PHARMACEUTICAL
World Journal of Pharmaceutical and Medical Research
AND MEDICAL RESEARCH ISSN 2455-3301
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A REVIEW ON MICROEMULSION FOR DRUG DELIVERY SYSTEM

Sagar R. Wagh, Mayur B. Patil, Aparna S. Musale, Harshal D. Mahajan, Rajendra D. Wagh

DCS’s A.R.A. College of Pharmacy, Dhule, Maharashtra 424005.

*Corresponding Author: Sagar R. Wagh

DCS’s A.R.A. College of Pharmacy, Dhule, Maharashtra 424005.

Article Received on 02/05/2023 Article Revised on 22/05/2023 Article Accepted on 12/06/2023

ABSTRACT
Microemulsion are clear, thermodynamically stable, isotropic liquid mixtures of oil, water and surfactant,
frequently in combination with a cosurfactant. The aqueous phase may contain salt(s) and/or other ingredients, and
the "oil" may actually be a complex mixture of different hydrocarbons and olefins. In contrast to ordinary
emulsions, microemulsions form upon simple mixing of the components and do not require the high shear
conditions generally used in the formation of ordinary emulsions.In addition, the size of the droplets in such
microemulsions remains constant and ranges from 100-1000 A0(10-100 nm), and has very low oil/water interfacial
tension. Because the droplet size is less than 25% of the wavelength of visible light,microemulsions are
transparent.[1,2]

KEYWORDS: Microemulsion, Surfactants, Co-surfactants, oils, Bioavailability.

Three distinct microemulsion solubilization systems that 2) Water in oil microemulsions where in water droplets
can be used for drugs are as follows: are dispersed in the continuous oil phase,
1) Oil in water Microemulsion where in oil droplets 3) Bi-continuous microemulsions where in
aredispersed in the continuous aqueous phase, microdomains of oil and water are interspersed
within the systems.

(A) (B) (C)

Fig. 1: (A) oil-in-water microemulsion (B) water-in-oil microemulsion (C) Bi-continuous microemulsions.[4]

All three types of microemulsions, the intebilized by an the components and do not require the high shear
appropriate combination of surfactants and/or co- conditions generally used in the formation of ordinary
surfactants.[3] emulsions. The two basic types of microemulsions are
direct (oil dispersed in water, o/w) and reversed (water
Definition of Micro-Emulsion dispersed in oil, w/o).[5-6] The microemulsion concept
“A micro emulsion is a system of water, oil and an was introduced in 1940s by Hoar and Schulman who
amphiphile which is a single optically isotropic and generated a clear single-phase solution by triturating a
thermodynamically stable liquid solution”. milky emulsion with hexanol [7]. They prepared the first
microemulsion by dispersing oil in an aqueous
INTRODUCTION surfactants solution and adding an alcohol as a co-
surfactant, leading to transparent stable formulation.
Microemulsions are clear, stable, isotropic liquid
Microemulsion is defined as microemulsion are clear,
mixtures of oil, water and surfactant, frequently in
transparent, thermodynamically stable dispersions of oil
combination with a co-surfactant. The aqueous phase
and water, stabilized by an interfacial film of surfactant
may contain salt(s) and/or other ingredients, and the "oil"
frequently in combination with a co-surfactant
may actually be a complex mixture of different [2].
Alternative names for these systems are often used,
hydrocarbons and olefins. In contrast to ordinary
such as swollen micelle, transparent emulsion,
emulsions, microemulsions form upon simple mixing of
solubilized oil and micellar solution. Microemulsions are

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Wagh et al. World Journal of Pharmaceutical and Medical Research

bi-continuous systems that are essentially composed of Oil- in- water microemulsion or winsor I
bulk phases of water and oil separated by a surfactant/co- In Oil-in-water type of microemulsions droplets of oil is
surfactant rich interfacial region.[8] The term of micro surrounded by a surfactant (and may be co-surfactant)
emulsion applies to a mixture with at least three film that forms the internal phase distributed in water,
components; an oily phase, an aqueous phase and a which is the continuous phase. This type of
surface active species, so called surfactants. Sometimes microemulsion generally has a larger interaction volume
the forth component i.e., co-surfactant can/must be than the w/o microemulsions.
present. Depending on the ratios between the
components, in the two extremes the microstructure of Water - in - oil microemulsion or winsor II
the micro emulsions vary microstructure of the micro In Water-in-oil type of microemulsions droplets of water
emulsions vary from a very tiny water droplets dispersed surrounded by a continuous oil phase. These are
in oil phase (w/o micro emulsion) to a oil droplets recognized as “reversemicelles”, where the polar
dispersed in water phase (o/w micro emulsion). headgroups of the surfactant are facing into the droplets
of water, with the fatty acid tails facing into the oil
Advantages of Microemulsion system.[9-12] phase. A w/o microemulsion used orally or parenterally
1. Microemulsions are easily prepared and require no may be destabilized by the aqueous biological system.
energy contribution during preparation this is due to
better thermodynamic stability. Bi-continuous microemulsion or winsor III
2. The formation of microemulsion is reversible. In bi-continuous microemulsion system the amount of
3. They may become unstable at low or high water and oil present are similar, In this case, both water
temperature but when the temperature returns to the and oil exist as a continuous phase. An irregular channel
stability range, the microemulsion reforms. of oil and water are combined, and looks like a “sponge-
4. Microemulsions are thermodynamically stable phase”. Transitions from o/w to w/o microemulsions
system and allows self-emulsification of the system. may pass through this bi-continuous state. Bi-continuous
5. Microemulsions have low viscosity compared to microemulsion, may show non-Newtonian flow and
emulsions. plasticity. These properties make them especially useful
6. Microemulsions act as super solvents for drug, can for topical delivery of drugs or for intravenous
solubilize both hydrophilic and lipophilic drugs administration.
including drugs that are insoluble in both aqueous
and hydrophobic solvents. Single phase homogeneous mixture or winsor IV
7. Having the ability to carry both lipophilic and In single phase homogeneous mixture or winsor IV the
hydrophilic drugs. oil, water and surfactants are homogenously mixed.
8. The dispersed phase, lipophilic or hydrophilic (O/W,
or W/O microemulsions) can act as a potential Methods of Preparation[17]
reservoir of lipophilic or hydrophilic drugs, • Dry Gum Method: Triturate mixture of emulsifier
respectively. and oil with addition of water which will form
9. The use of microemulsion as delivery systems can primary emulsion. Further add water to dilute and
improve the efficacy of a drug, allowing the total mix continuously to form emulsion.
dose to be reduced and thus minimizing side effects. • Wet Gum Method: Initially triturate oil with water
and then with emulsifier to form primary emulsion.
Disadvantages of Microemulsion Systems[9-11] Further add water, dilute and mix to form emulsion.
1. Having limited solubilizing capacity for high- • In Situ Soap Method: Take oil and lime water
melting substances. (calcium hydroxide solution). Mix with stirring to
2. Require large amount of Surfactants for stabilizing form emulsion.
droplets. • Mechanical Method: Take oil, water and emulsifier
3. Microemulsion stability is influenced by together, mix well and stir by machine to form
environmental parameters such as temperature and emulsion.
pH.

Types of Microemulsions[13-16]
Microemulsions are thermodynamically stable, but are
only found under carefully defined conditions.
According to Winsor, there are four types of
microemulsion phases exists in equilibria, these phases
are also referred as Winsor phases. They are,
1. Oil- in- water microemulsion or winsor I
2. Water – in oil microemulsion or winsor II
3. Bicontinuousmicroemulsion or winsor III
4. Single phase homogeneous mixture or winsor IV

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Wagh et al. World Journal of Pharmaceutical and Medical Research

Comparison between Microemulsion & Emulsion

Sr. Emulsion Micro-emulsion
1. Emulsion is Biphasic Micro-emulsion is Monophasic
Stability is Thermodynamically unstable but Stability is Thermodynamically stable but
2.
Kinetically stable Kinetically unstable
3. Droplet size about >500 nm Droplet size about 20-200 nm
4. Structure of micro-emulsion Static in nature Structure of micro-emulsion Dynamic in nature
5. Interfacial tension is High Interfacial tension is low
6. Appearance of emulsion is cloudy Appearance of emulsion is transparent

Composition Co-surfactants
The major components of micro emulsion system are: It is studied that high concentrations of single-chain
1) Oil phase surfactants are required to reduce the O/W interfacial
2) Surfactant (Primary surfactant) tension to a level to enable a spontaneous formation of a
3) Co-surfactant (Secondary surfactant) microemulsion. However, if co-surfactants are added
4) Co-Solvent then with minimum concentration of surfactants different
curvatures of interfacial film can be formed to generate
Oil phase stable micro emulsion composition.[20-25] Co surfactants
Oil phase is second most important vehicle after water raises the fluidity of the interface due to presence of
due to its properties to solubilize lipophilic drug fluidizing groups like unsaturated bonds, then
molecules and improve absorption through lipid layer demolishes liquid crystalline or gel structure and alters
present in body[18].Oil has unique property of penetrating the HLB value in such way to cause spontaneous
cell wall and hence very useful for lipophilic active drug formation of micro emulsion.
delivery. Swelling of tail group region of the surfactant is
influence by oil phase. Such penetration is to greater Example
extent in case of short chain alkanes as compared to long Short chain alcohols like ethanol to butanol
chain alkanes.[19]. Short chain glycols like propylene glycol
Example; Medium chain alcohols like amines or acids

Saturated fatty acids: lauric, myristic and capric acid Co-solvents

Unsaturated fatty acids: oleic acid, linoleic acid and Co-solvents are organic solvents like ethanol, propylene
linolenic acid glycol (PG), and polyethylene glycol (PEG) which helps
Fatty acid esters: ethyl or methyl esters of lauric, to dissolve relatively high concentrations of surfactants
myristic and oleic acid as well as lipid soluble drugs. Hence co-solvents are also
considered as co-surfactants.
Surfactants
During the preparation of the microemulsion, surfactant Theories of Micro Emulsion Formation[26,27]
must be able to reduce the interfacial tension nearest to Historically, three approaches have been used to explain
zero to facilitate dispersion of all components. These micro emulsion formation and stability. They are as
surfactants can be: follows-
Non-ionic 1- Interfacial or mixed film theories.
Anionic 2- Solubilization theories
Cationic 3- Thermodynamic treatments
Zwitterionic,
Nature of surfactants helps in deciding stability of The free energy of micro emulsion formation can be
microemulsion. Dipole and hydrogen bond interactions considered to depend on the extent to which surfactant
stabilizes non-ionic surfactant and electrical double layer lowers the surface tension of the oil water interface and
stabilizes ionic surfactants. Ionic surfactants are also change in entropy of the system such that,
affected by salt concentration. Gf = γ a - T S

Examples of non-ionic surfactants Where,

Polyoxyl 35 castor oil (Cremophor EL) Gf = free energy of formation
Polyoxyl 40 hydrogenated castor oil (Cremophor RH 40) A = change in interfacial area of micro emulsion
Polysorbate20(Tween20) S = change in entropy of the system
Polysorbate80(Tween80) T = temperature
d-α-tocopherolpolyethylene glycol1000succinate(TPGS) γ = surface tension of oil water interphase.
SolutolHS-15
Sorbitanmonooleate(Span80) When micro emulsion is formed the change in A is very
Polyoxyl40 stearate etc. large due to the large number of very small droplets

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Wagh et al. World Journal of Pharmaceutical and Medical Research

formed. In order for a micro emulsion to be formed assessing flocculation since electrical charges on
(transient) negative value was required, it is recognized particles influence the rate of flocculation.
that while value of A is positive at all times, it is very
small and it is offset by the entropic component. The 5) Poly dispersity
dominant favorable entropic contribution is very large This property is characterized by Abbes refractometer.
dispersion entropy arising from the mixing of one phase
in the other in the form of large number of small Factors Affecting Microemulsions[28,29,30]
droplets. However there are also expected to be favorable Factor affecting the micro-emulsion are as follows
entropic contributions arising from other dynamic a) Packing ratio
processes such as surfactant diffusion in the interfacial b) Property of surfactant
layer and monomer-micelle surfactant exchange. Thus a c) Property of oil phase
negative free energy of formation is achieved when large d) Temperature
reductions in surface tension are accompanied by e) Chain length
significant favorable entropic change. In such cases, f) Nature of co-surfactant
micro emulsion is spontaneous and the resulting
dispersion is thermodynamically stable. Applications of Micro Emulsion
1) Pharmaceutical Applications
Limitations During the last two decades, microemulsions have been
Some factors limit the use of microemulsion in promisingly used as drug delivery system for its
pharmaceutical applications. advantages include their thermodynamic stability, optical
1. The need of pharmaceutically acceptable ingredients clarity and ease of penetration. The role of
limits the choice of microemulsion components microemulsion as drug delivery system shall be
(e.g., oil, surfactant and co-surfactants) leading to discussed here in.
difficulties in formulation.
2. The concentration of surfactants and co-surfactants 2) Oral delivery
used must be kept low for toxicological reasons. The development of effective oral delivery systems has
3. Microemulsion also suffers from limitations of always been challenging to researchers because drug
phase separation. efficacy can be restricted by instability or poor solubility
4. For intravenous use, the demand of toxicity on the in the gastrointestinal fluid. Microemulsions have the
formulation is rigorous and very few studies have potential to enhance the solubilization of poorly soluble
been reported so far. drugs (particularly BCS class II or class IV) and
5. The major limitation is the toxicity of excipients i.e. overcome the dissolution related bioavailability
surfactant/ co-surfactants. Exploration of safe problems. Due to the presence of polar, non-polar and
excipients and evaluation of the toxicity parameters interfacial domains, hydrophilic drugs including
of available excipients may help in further macromolecules can be encapsulated with varying
expansion of research in this field. solubility. These systems have been protecting the
incorporated drugs against oxidation, enzymatic
Identification Tests for Microemulsion degradation and enhance membrane permeability.
1) Dilution test Presently, Sand immune Neoral(R) (Cyclosporine A),
If the continuous phase is added in micro emulsions, it Fortovase(R) (Saquinavir), Norvir(R) (Ritonavir) etc. are
will not crack or separate into phases. If water is added the commercially available microemulsion formulations.
in o/w type of micro emulsions it will remain stable. Microemulsion formulation can be potentially useful to
improve the oral bioavailability of poorly water soluble
2) Staining test drugs by enhancing their solubility in gastrointestinal
Water soluble dye such as methylene blue or amaranth is fluid.
added in water and micro emulsion is prepared with oil
and surfactant. A drop of Microemulsions is observed 3) Parenteral delivery
under microscope. Background is found to be blue / red The formulation of Parenteral dosage form of lipophilic
and globule will appear colourless respectively. and hydrophilic drugs has proven to be difficult. O/w
microemulsions are beneficial in the Parenteral delivery
3) Dilute ability test of sparingly soluble drugs where the administration of
The Micro emulsions formed is diluted in 1:10, and suspension is not required. They provide a means of
1:100, ratios with double distilled water to check if the obtaining relatively high concentration of these drugs
system shows any signs of separation. which usually requires frequent administration. Other
advantages are that they exhibit a higher physical
4) Zeta potential measurement stability in plasma than liposome’s or other vehicles and
It must be negative or neutral, which indicate that the internal oil phase is more resistant against drug
droplets of micro emulsion having no charge and hence leaching. Several sparingly soluble drugs have been
the system is stable. Zeta potential is determined by formulated into o/w microemulsion for parenteral
using Zetasizer. Zeta potential is essentially useful for delivery. An alternative approach was taken by Von

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Wagh et al. World Journal of Pharmaceutical and Medical Research

Corse want and Thoren in which C3-C4 alcohols were 4. Lawrencea JM and Gareth RD. Microemulsion-
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