Madhav and Gupta, IJPSR, 2011; Vol.

2(8): 1888-1899 ISSN: 0975-8232

IJPSR (2011), Vol. 2, Issue 8 (Review Article)

Received on 07 April, 2011; received in revised form 12 May, 2011; accepted 16 July, 2011

A REVIEW ON MICROEMULSION BASED SYSTEM

S. Madhav and D. Gupta

Faculty of Pharmacy, Dehradun institute of Technology, Dehradun, Uttarakhand, India

ABSTRACT

Keywords: Microemulsions are clear, stable, isotropic mixtures of oil, water and
Microemulsion, surfactant, frequently in combination with a cosurfactant. Microemulsions
Surfactants, act as potential drug carrier systems for oral, topical, and parenteral
Co-surfactants, administration. They offer the advantage of spontaneous formation, ease of
Oil manufacturing and scale-up, thermodynamic stability, and improved drug
Correspondence to Author: solubilization and bioavailability. Preparing a pharmaceutically acceptable
dosage form demands a clear understanding of the micro-emulsion
Prof. (Dr.) N. V. Satheesh Madhav
structure, phase behavior, factors leading to its thermodynamic stability and
Director, Faculty of Pharmacy, D.I.T, the potential uses and limitations of the microemulsion system. Knowledge
Makkawala green, P.O Bhagwatpur, of the various methods available to thoroughly characterize a microemulsion
Mussorie Diversion Road, Dehradun, system is essential. While microemulsion is used in several fields, in this
Uttarakhand, India
review the pharmaceutical applications are emphasized. Several references
are cited, but the list is by no means exhaustive. The review is written so that
a newcomer to the field can easily grasp the important facts pertaining to
this novel delivery system.

INTRODUCTION: Microemulsions are clear, stable, groups in the aqueous phase. As in the binary systems
isotropic liquid mixtures of oil, water and surfactant, (water/surfactant or oil/surfactant), self-assembled
frequently in combination with a cosurfactant. The structures of different types can be formed, ranging,
aqueous phase may contain salt(s) and/or other for example, from (inverted) spherical and cylindrical
ingredients, and the "oil" may actually be a complex micelles to lamellar phases and bi-continuous
mixture of different hydrocarbons and olefins. In microemulsions, which may coexist with
contrast to ordinary emulsions, microemulsions form predominantly oil or aqueous phases.
upon simple mixing of the components and do not
require the high shear conditions generally used in the
formation of ordinary emulsions. The two basic types
of microemulsions are direct (oil dispersed in water,
o/w) and reversed (water dispersed in oil, w/o) 1-3.

In ternary systems such as microemulsions, where two

immiscible phases (water and ‘oil’) are present with a
surfactant, the surfactant molecules may form a
monolayer at the interface between the oil and water,
with the hydrophobic tails of the surfactant molecules
dissolved in the oil phase and the hydrophilic head FIG. 1: MICROEMULSIONS.
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In principle, microemulsions can be used to deliver formulations in transdermal delivery of lipophilic

drugs to the patients via several routes, but the topical drugs. A unique attempt was made 18 to emulsify
application of microemulsions has gained increasing coconut oil with the help of polyoxyethylene 2-cetyl
interest. The three main factors determining the ether (Brij 52) and isopropanol or ethanol, forming
transdermal permeation of drugs are the mobility of stable isotropic dispersion thus paving way for use of
drug in the vehicle, release of drug from the vehicle, plant and vegetable oil to be used as oil phase in
and permeation of drug into the skin. These factors microemulsion.
affect either the thermodynamic activity that drives
the drug into the skin or the permeability of drug in Theory: Various theories concerning microemulsion
the skin, particularly stratum corneum. formation, stability and phase behavior have been
proposed over the years. For example, one explanation
Microemulsions improve the transdermal delivery of for their thermodynamic stability is that the oil/water
several drugs over the conventional topical dispersion is stabilized by the surfactant present and
preparations such as emulsions 4, 5 and gels 6, 7. their formation involves the elastic properties of the
Mobility of drugs in microemulsions is more facile 8, as surfactant film at the oil/water interface, which
compared to the microemulsion with gel former which involves as parameters, the curvature and the rigidity
will increase its viscosity and further decrease the of the film. These parameters may have an assumed or
permeation in the skin 9. The superior transdermal flux measured pressure and/or temperature dependence
from microemulsions has been shown to be mainly (and/or the salinity of the aqueous phase), which may
due to their high solubilization potential for lipophilic be used to infer the region of stability of the
and hydrophilic drugs. microemulsion, or to delineate the region where three
coexisting phases occur, for example. Calculations of
This generates an increased thermodynamic activity the interfacial tension of the microemulsion with a
towards the skin. Microemulsions may affect the coexisting oil or aqueous phase are also often of
permeability of drug in the skin. In this case, the special focus and may sometimes be used to guide
components of microemulsions serve as permeation their formulation.
enhancers 10-12. Several compounds used in
microemulsions have been reported to improve the Historical Background: The combination of water and
transdermal permeation by altering the structure of oil, made into a single-phase system with the aid of a
the stratum corneum 13-15. For example, short chain third component (surfactant), was patented in mid
alkanols are widely used as permeation 16 enhancers. It 1930’s 19. However, it was not until 1943 when the first
is known that oleic acid, a fatty acid with one double academic studies were performed 20. Hoar and
bond in the chain structure, perturbs the lipid barrier Schulman showed, with the help of a strong surface-
in the stratum corneum by forming separate domains active agent, it is possible to induce spontaneous
which interfere with the continuity of the emulsification. This is now attributed to microemulsion
multilamellar stratum corneum and may induce highly formation, owing to very low interfacial tensions
permeable pathways in the stratum corneum. promoted by the surfactants. Five years later, Winsor
21
studied the phase behaviour of water-oil-surfactant
Isopropyl myristate (IPM) is used as a permeation mixtures in the presence of different additives and
enhancer in transdermal formulations, but the classified four types of phase equilibria:
mechanism of its action is poorly understood. Nonionic
surfactants are widely used in topical formulations as Type I: Surfactant-rich water phase (lower phase)
solubilizing agents but some recent results indicate coexists with surfactant-poor oil phase (Winsor I).
that they may affect also the skin barrier function17. It Type II: Surfactant-rich oil phase (the upper phase)
is of interest to explore the effects of these coexists with surfactant-poor water phase (Winsor II).
components in the organized microemulsion Type III: Surfactant rich middle-phase coexists with
structures. The aim of the present study was to both water (lower) and oil (upper) surfactant-poor
investigate the potential of several microemulsion phases (Winsor III).

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Type IV: Single phase homogeneous mixture. systems can be in equilibrium with other phases, many
systems, especially those with high volume fractions of
In 1959, Schulman et al., 22 titrated a multiphase both the two immiscible phases, can be easily
system (consisting of water, oil and surfactant) with destabilized by anything that changes this equilibrium
alcohol and obtained a transparent solution which e.g. high or low temperature or addition of surface
they termed ’a microemulsion’. At that early stage tension modifying agents.
some researchers preferred to identify these systems
with ‘swollen micelles’ 23, others used the term However, examples of relatively stable microemulsions
‘micellar emulsion’ 24. Nevertheless, the term can be found. It is believed that the mechanism for
‘microemulsion’ is a commonly used name nowadays. removing acid build up in car engine oils involves low
A detailed historical background of microemulsions water phase volume, water-in-oil (w/o)
can be found elsewhere 25. microemulsions. Theoretically, transport of the
aqueous acid droplets through the engine oil to micro-
Phase Diagrams: The microemulsion region is usually dispersed calcium carbonate particles in the oil should
characterized by constructing ternary-phase diagrams. be most efficient when the droplets are small enough
Three components are the basic requirement to form a to transport a single hydrogen ion (the smaller the
microemulsion: an oil phase, an aqueous phase and a droplets, the greater the number of droplets, the
surfactant. If a cosurfactant is used, it may sometimes faster the neutralization). Such microemulsions are
be represented at a fixed ratio to surfactant as a single probably very stable across a reasonably wide range of
component, and treated as a single "pseudo- elevated temperatures.
component". The relative amounts of these three
components can be represented in a ternary phase
diagram. Gibbs phase diagrams can be used to show
the influence of changes in the volume fractions of the
different phases on the phase behavior of the system
26
.

The three components composing the system are each

found at an apex of the triangle, where their
corresponding volume fraction is 100%. Moving away
from that corner reduces the volume fraction of that
specific component and increases the volume fraction
of one or both of the two other components. Each
point within the triangle represents a possible
composition of a mixture of the three components or
pseudo-components, which may consist (ideally, FIG. 2: SCHEMATIC REPRESENTATION OF PSEUDO TERNARY
according to the Gibbs' phase rule) of one, two or PHASE DIAGRAM SHOWING MICROEMULSION REGION 27
three phases. These points combine to form regions
Three types of microemulsions are most likely to be
with boundaries between them, which represent the
formed depending on the composition:
"phase behavior" of the system at constant
temperature and pressure.  Oil in water microemulsions wherein oil droplets
are dispersed in the continuous aqueous phase
The Gibbs phase diagram, however, is an empirical
visual observation of the state of the system and may,  Water in oil microemulsions wherein water
or may not express the true number of phases within a droplets are dispersed in the continuous oil phase;
given composition. Apparently clear single phase
formulations can still consist of multiple iso-tropic  Bi-continuous microemulsions wherein micro-
phases (e.g. the apparently clear heptane/AOT/water domains of oil and water are inter-dispersed
microemulsions consist multiple phases). Since these within the system.

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In all three types of microemulsions, the interface is emulsions are cloudy while microemulsions are clear
stabilized by an appropriate combination of the or translucent. In addition, there are distinct
surfactants and/or co-surfactants. The key difference differences in their method of preparation, since
between emulsions and microemulsions are that the emulsions require a large input of energy while
former, whilst they may exhibit excellent kinetic microemulsions do not. The latter point has obvious
stability, are fundamentally thermodynamically implications when considering the relative cost of
unstable and will eventually phase separate 1. Another commercial production of the two types of system.
important difference concerns their appearance;
TABLE 1: COMPARISON WITH EMULSIONS (MACROEMULSIONS) 28-33
Emulsions (Macroemulsions) Microemulsions

FIG. 3: EMULSIONS FIG. 4: MICROEMULSIONS

They constantly evolve between various structures ranging
Emulsions consist of roughly spherical droplets of one phase dispersed
from droplet like swollen micelles to bi-continuous
into the other.
structure.

Droplet diameter: 1 – 20 mm. 10 – 100 nm

Most emulsions are opaque (white) because bulk of their droplets is Microemulsions are transparent or translucent as their
greater than wavelength of light and most oils have higher refractive droplet diameter are less than ¼ of the wavelength of light,
indices than water. they scatter little light.

Microemulsion droplet may disappear within a fraction of a

Ordinary emulsion droplets, however small exist as individual entities
second whilst another droplet forms spontaneously
until coalescence or ostwald ripening occurs.
elsewhere in the system.

More thermodynamically stable than macroemulsions and

They may remain stable for long periods of time, will ultimately
can have essentially infinite lifetime assuming no change in
undergo phase separation on standing to attain a minimum in free
composition, temperature and pressure, and do not tend to
energy. They are kinetically stable thermodynamically unstable.
separate.

They are on the borderline between lyophobic and lipophilic

They are lyophobic.
colloids.

Require intense agitation for their formation. Generally obtained by gentle mixing of ingredients.

Theory of microemulsion formulation: Microemulsion the surface tension of the oil–water interface and the
formation and stability can be explained on the basis change in entropy of the system such that 34,
of a simplified thermodynamic rationalization. The free
energy of microemulsion formation can be considered DG f = γDA - T DS
to depend on the extent to which surfactant lowers
Where, DG f =free energy of formation, γ = Surface
tension of the oil–water interface, DA =Change in

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 Madhav and Gupta, IJPSR, 2011; Vol. 2(8): 1888-1899 ISSN: 0975-8232

interfacial area on microemulsification, DS = Change in account the relative contribution of hydrophilic and
entropy of the system which is effectively the hydrophobic fragments of the surfactant molecule. It is
dispersion entropy, and T = Temperature. generally accepted that low HLB (3-6) surfactants are
favored for the formation of w/o microemulsions
It should be noted that when a microemulsion is whereas surfactants with high HLBs (8-18) are
formed, the change in DA is very large due to the large preferred for the formation of o/w microemulsion
number of nanodroplets are formed. It is seen that systems. Ionic surfactants such as sodium dodecyl
while the value of γ is positive at all times, it is very sulphate which have HLBs greater than 20, often
small (of the order of fractions of mN/m), and is offset require the presence of a co-surfactant to reduce their
by the entropic component. The dominant favorable effective HLB to a value within the range required for
entropic contribution is the very large dispersion microemulsion formation. In contrast, the CPP relates
entropy arising from the mixing of one phase in the the ability of surfactant to form particular aggregates
other in the form of large numbers of nanodroplets. to the geometry of the molecule itself.
However, favorable entropic contributions also arise
from other dynamic processes such as surfactant A combination of these, particularly ionic and non-
diffusion in the interfacial layer and monomer-micelle ionic, can be very effective at increasing the extent of
surfactant exchange. the microemulsion region. Examples of non-Ionics
include polyoxyethylene surfactants such as Brij
Thus, a negative free energy of formation is achieved 35(C12E35) or sugar esters such as sorbitan monooleate
when large reductions in surface tension are (Span 80). Phospholipids are a notable example of
accompanied by significant favorable entropic change. zwitter ionic surfactants and exhibit excellent
In such cases, microemulsification is spontaneous and biocompatibility. Lecithin preparations from a variety
the resulting dispersion is thermodynamically stable. of sources including soybean and egg are available
Though, it has been know that several factors commercially and contain diacylphosphatidylcholine as
determine whether a w/o or o/w microemulsion its major constituent 38-41.
system will be formed but in general it could be Quaternary ammonium alkyl salts form one of the best
summarized that the most likely microemulsion would known classes of cationic surfactants, with
be that in which the phase with the smaller volume hexadecyltrimethyl ammonium bromide (CTAB) (Rees
fraction forms. et al., 1995), and the twin-tailed surfactant
Surfactants, co-surfactants and oil used in didodcecylammonium bromide (DDAB) are amongst
microemulsion formulation: the most well known (Olla et al., 1999). The most
widely studied anionic surfactant is probably sodium
 Surfactants- used to stabilize the system; -non- bis-2-ethylhexylsulphosuccinate (AOT) which is twin-
ionic, zwitter ion, cationic or anionic. tailed and is a particularly effective stabiliser of w/o
microemulsions 42.
 Co-surfactant- decrease the interfacial tension;
-and increase the microemulsion region; - In most cases, single-chain surfactants alone are
alcohols, amines, and cholesterol unable to reduce the oil /water interfacial tension
sufficiently to enable a microemulsion to form, a point
 Oils- hydrocarbon oils such as heptane or - made in a number of pertinent microemulsions
cyclic oils like cyclohexane the droplets i.e., reviews43-47. Medium chain length alcohols which are
internal phase. commonly added as co-surfactants have the effect of
further reducing the interfacial tension, whilst
Attempts have been made to rationalize surfactant
increasing the fluidity of the interface thereby
behavior in terms of the hydrophilic- lipophilic balance
increasing the entropy of the system. Medium chain
(HLB) 35, as well as the critical packing parameter (CPP)
36, 37 length alcohols also increase the mobility of the
. Both approaches are fairly empirical but can be a
hydrocarbon tail and also allow greater 44, 45.
useful guide to surfactant selection. The HLB takes into

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TABLE 2: COMMON EXCIPIENTS USED TO FORMULATE 8. The formation of microemulsion is reversible.

MICROEMULSIONS They may become unstable at low or high
Oils Surfactant Co-surfactant
temperature but when the temperature returns to
Oleic acid polysorbate20 ethanol the stability range, the microemulsion reforms.
Castor oil polysorbate 80 Glycerine
Corn oil polyoxyl 35 castor oil PEG 300 Disadvantages of Microemulsion Based Systems 48:
Peanut oil polyoxyl 60 castor oil poloxamer 407
Sesame oil PEG 300 caprylic propylene glycol 1. Use of a large concentration of surfactant and co-
surfactant is necessary for stabilizing the droplets
Advantages of Microemulsion Based Systems 33: of microemulsion.
Microemulsions exhibits several advantages as a drug 2. Limited solubilizing capacity for high-melting
delivery system: substances used in the system.
3. The surfactant should be nontoxic for use in
1. Microemulsions are thermodynamically stable pharmaceutical applications.
system and the stability allows self-emulsification 4. Microemulsion stability is influenced by
of the system. environmental parameters such as temperature
2. Microemulsions act as supersolvents for drug.
and pH. These parameters change as
They can solubilize both hydrophilic and lipophilic microemulsion delivered to patients.
drugs including drugs that are relatively insoluble
in both aqueous and hydrophobic solvents. Limitations: Some factors limit the use of
3. The dispersed phase, lipophilic or hydrophilic (oil- microemulsion in pharmaceutical applications.
in-water, O/W, or water-in-oil, W/O
microemulsions) can act as a potential reservoir of 1. The need of pharmaceutically acceptable
lipophilic or hydrophilic drugs, respectively. Drug ingredients limits the choice of microemulsion
release with pseudo-zero-order kinetics can be components (e.g., oil, surfactant and
obtained, depending on the volume of the cosurfactants) leading to difficulties in
dispersed phase, the partition of the drug and the formulation.
transport rate of the drug. 2. The concentration of surfactants and co-
4. The mean diameter of droplets in microemulsion surfactants used must be kept low for toxicological
is below 0.22 mm. The small size of droplet in reasons.
microemulsions e.g. below 100 nm, yields very 3. Microemulsion also suffers from limitations of
large interfacial area, from which the drug is phase separation.
released rapidly into external phase when 4. For intravenous use, the demand of toxicity on the
absorption (in vitro or in vivo) takes place, formulation is rigorous and very few studies have
maintaining the concentration in the external been reported so far.
phase close to initial levels. 5. The major limitation is the toxicity of excipients
5. Same microemulsions have the ability to carry i.e. surfactant/ co-surfactants. Exploration of safe
both lipophilic and hydrophilic drugs. excipients and evaluation of the toxicity
6. Because of thermodynamic stability of parameters of available excipients may help in
microemulsions, they are easy to prepare and further expansion of research in this field.
require no significant energy contribution during
Preparation of Microemulsion system: The drug is be
preparation. Microemulsions have low viscosity
dissolved in the lipophilic part of the microemulsion
compared to primary and multiple emulsions.
i.e. oil and the water phases can be combined with
7. The use of microemulsion as delivery systems can
surfactant and then cosurfactant is added at slow rate
improve the efficacy of a drug, allowing the total
with constant stirring until the system is transparent.
dose to be reduced and thus minimizing side
The amount of surfactant and cosurfactant to be
effects.
added and the percent of oil phase that can be
incorporated is determined with the help of pseudo-

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ternary phase diagram. Ultrasonicator can finally be microemulsion region was considerably large since 1-
used so to achieve the desired size range for dispersed butanol acted as a cosurfactant and interacted with
globules. It is then allowed to equilibrate. Gel may be the surfactant monolayer to increase the flexibility of
prepared by adding a gelling agent to the above the interfacial film.
microemulsion. Carbomers (crosslinked polyacrylic
acid polymers) are the most widely used gelling agent. Characterization of Microemulsion: The droplet size,
viscosity, density, turbidity, refractive index, phase
Construction of Phase Diagram: Pseudo-ternary phase separation and pH measurements shall be performed
diagrams of oil, water, and co-surfactant/surfactants to characterize the microemulsion.
mixtures are constructed at fixed cosurfactant/
surfactant weight ratios. Phase diagrams are obtained 1. Droplet size: The droplet size distribution of
by mixing of the ingredients, which are pre-weighed microemulsion can be determined by either light
into glass vials and titrated with water and stirred well scattering technique or electron microscopy. This
at room temperature. Formation of technique has been suggested as the best method
Monophasic/Biphasic system is confirmed by visual for predicting microemulsion stability.
inspection. In case turbidity appears followed by a  Dynamic Light-Scattering Measurements: The
phase separation, the samples are considered as
DLS measurements are taken at 90° in a
biphasic system. Monophasic, clear and transparent dynamic light-scattering spectrophotometer
mixtures are visualized after stirring and the samples using a neon laser of wavelength 632 nm. The
are marked as points in the phase diagram. The area data is processed by the built-in computer with
covered by these points is considered as the the instrument.
microemulsion region of existence.
 Polydispersity: Polydispersity is studied using
Abbe refractometer.

 Phase analysis: The type of microemulsion

forming the phase system (o/w or w/o) is
determined by measuring the electrical
conductivity using a conductometer.

2. Viscosity Measurement: The viscosity of

microemulsions of several compositions is
measured at different shear rates at different
temperatures using Brookfield type rotary
viscometer. The sample room of the instrument
must be maintained at 37 ± 0.2°C by a
thermobath, and the samples for the
measurement are to be immersed in it before
testing.

3. In-vitro Drug Permeation Studies

FIGURE 5: THE PSEUDOTERNARY PHASE DIAGRAM OF
IPP/WATER/BRIJ 97:1-BUTANOL (2:1) AND THE DILUTION LINE
 Determination of permeability coefficient and
FOR INVESTIGATION AT 45% WT/WT SURFACTANT SYSTEM 49
flux: Excised human cadaver skin from the
Figure 5 shows the pseudoternary phase diagram with abdomen is used for permeation study. The
the area inside the frame assigned on the phase skin is stored at 4oC and the epidermis
diagram showing the microemulsion region. The area separated. The skin is first immersed in purified
outside the frame indicates a turbid region with water at 60oC for 2 min and the epidermis then
multiphase systems. It could be noted that the area of peeled off. Dried skin samples can be kept at -

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200C for later use. Alternatively the full Pharmacological Studies: Therapeutic effectiveness is
thickness dorsal skin of male hairless mice may evaluated for the specific pharmacological action that
be used. The skin shall be excised, washed with the drug purports to show as per stated guidelines.
normal saline and then used. The passive
permeability of lipophilic drug through the skin Estimation of Skin Irritancy: As the formulation is
is investigated using Franz diffusion cells with intended for dermal application skin irritancy should
known effective diffusional area. The hydrated be tested. The dorsal area of the trunk is shaved with
skin samples are used for the study. The clippers 24 hours before the experiment. The skin shall
receiver compartment contains a complexing be scarred with a lancet. 0.5 ml of product is applied
agent like cyclodextrin in the receiver phase, and then covered with gauze and a polyethylene film
which increases the solubility and allows the and fixed with hypoallergenic adhesive bandage. The
maintenance of sink conditions in the test be removed after 24 hours and the exposed skin is
experiments. Samples are withdrawn at regular graded for formation of edema and erythema. Scoring
interval and analyzed for amount of drug is repeated 72 hours later. Based on the scoring the
released. formulation shall be graded as ‘non-irritant’, ‘irritant’
and ‘highly irritant’.
4. In- vivo Studies:
Stability Studies: The physical stability of the
 Bioavailability studies: Skin bioavailability of microemulsion shall be determined under different
topical applied microemulsion on rats: Male storage conditions (4, 25 and 40°C) for 12 months.
Sprague–Dawley rats (400–500 g) are needed
to be anesthetized (15 mg/kg pentobarbital Fresh preparations as well as those that have been
sodium i.p.) and placed on their back. The hair kept under various stress conditions for extended
on abdominal skin is trimmed off and then period of time are subjected to droplet size
bathed gently with distilled water. Anesthesia distribution analysis. Effect of surfactant and their
should be maintained with 0.1-ml concentration on size of droplet are also studied.
pentobarbital (15 mg/ml) along the Applications of Microemulsions:
experiment. Microemulsions is applied on the
skin surface (1.8 cm2) and glued to the skin by a  Pharmaceutical Applications
silicon rubber. After 10, 30 and 60 min of invivo
study, the rats are killed by aspiration of ethyl 1. Parenteral delivery.
ether. The drug exposed skin areas is swabbed 2. Oral drug delivery.
three to four times with three layers of gauze
pads, then bathed for 30 s with running water, 3. Topical drug delivery.
wiped carefully, tape-stripped (X10 strips) and
harvested from the animals. 4. Ocular and pulmonary delivery.

 Determination of residual drug remaining in 5. Microemulsions in biotechnology.

the skin on tropical administration: The skin in
Parenteral Delivery: Parenteral administration
the above permeation studies can be used to
(especially via the intravenous route) of drugs with
determine the amount of drug in the skin. The
limited solubility is a major problem in industry
skin cleaned with gauze soaked in 0.05%
because of the extremely low amount of drug actually
solution of sodium lauryl sulfate and is bathed
delivered to a targeted site. Microemulsion
with distilled water. The permeation area is cut
formulations have distinct advantages over
and weighed and drug content is determined in
macroemulsion systems when delivered parenterally
the clear solution obtained after extracting
because of the fine particle microemulsion is cleared
with a suitable solvent and centrifuging.
more slowly than the coarse particle emulsion and,
therefore, have a longer residence time in the body.

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Both o/w and w/o microemulsion are used for of the drug to affected area of the skin or eyes. Both
parenteral delivery. The literature contains the details O/W and W/O microemulsions have been evaluated in
of the many microemulsion systems, few of these can a hairless mouse model for the delivery of
be used for the parenteral delivery because the prostaglandin E1 53.The microemulsions were based on
toxicity of the surfactant and parenteral use. An oleic acid or Gelucire 44/14 as the oil phase and were
alternative approach was taken by Von Corsewant and stabilized by a mixture of Labrasol (C8 and C10
Thoren 50 in which C3-C4 alcohols were replaced with polyglycolysed glycerides) and Plurol Oleique CC 497 as
parenterally acceptable co-surfactants, polyethylene surfactant.
glycol (400) / polyethylene glycol (660) 12-
hydroxystearate / ethanol, while maintaining a flexible Although enhanced delivery rates were observed in
surfactant film and spontaneous curvature near zero the case of the o/w microemulsion, the authors
to obtain and almost balanced middle phase concluded that the penetration rates were inadequate
microemulsion. The middle phase structure was for practical use from either system. The use of
preferred in this application, because it has been able lecithin/IPP/water microemulsion for the transdermal
to incorporate large volumes of oil and water with a transport of indomethacin and diclofenac has also
minimal concentration of surfactant. been reported. Fourier transform infra red (FTIR)
spectroscopy and differential scanning calorimetry
Oral Delivery: Microemulsion formulations offer the (DSC) showed the IPP organogel had disrupted the
several benefits over conventional oral formulation for lipid organisation in human stratum corneum after a 1
oral administration including increased absorption, day incubation 54.
improved clinical potency and decreased drug toxicity
51
. Therefore, microemulsion has been reported to be The transdermal delivery of the hydrophilic drug
ideal delivery of drugs such as steroids, hormones, diphenhydramine hydrochloride from a w/o
diuretic and antibiotics. microemulsion through the excised human skin has
also been investigated. The formulation was based on
Pharmaceutical drugs of peptides and proteins are combinations of Tween 80 and Span 20 (surfactants)
highly potent and specific in their physiological with IPM. However two additional formulations were
functions. However, most are difficult to administer tested containing cholesterol and oleic acid,
orally. With on oral bioavailability in conventional (i.e. respectively. Cholesterol increased drug penetration
non-microemulsion based) formulation of less than whereas oleic acid had no measurable effect, but the
10%, they are usually not therapeutically active by oral authors clearly demonstrated that penetration
administration. Because of their low oral characteristics can be modulated by compositional
bioavailability, most protein drugs are only available as selection 55.
parenteral formulations. However, peptide drugs have
an extremely short biological half life when Ocular and Pulmonary Delivery: For the treatment of
administered parenterally, so require multiple dosing. eye diseases, drugs are essentially delivered topically.
O/W microemulsions have been investigated for ocular
A microemulsion formulation of cyclosporine, named administration, to dissolve poorly soluble drugs, to
Neoral® has been introduced to replace Sandimmune®, increase absorption and to attain prolong release
a crude oil-in-water emulsion of cyclosporine profile.
formulation. Neoral® is formulated with a finer
dispersion, giving it a more rapid and predictable The microemulsions containing pilocarpine were
absorption and less inter and intra patient variability 52. formulated using lecithin, propylene glycol and PEG
200 as co-surfactant and IPM as the oil phase. The
Topical Delivery: Topical administration of drugs can formulations were of low viscosity with a refractive
have advantages over other methods for several index lending to ophthalmologic applications 56. The
reasons, one of which is the avoidance of hepatic first formation of a water-in-HFA propellant microemulsion
pass metabolism of the drug and related toxicity stabilized by fluorocarbon non-ionic surfactant and
effects. Second is the direct delivery and targetability intended for pulmonary delivery has been described.

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 Madhav and Gupta, IJPSR, 2011; Vol. 2(8): 1888-1899 ISSN: 0975-8232

Microemulsions in Biotechnology: Many enzymatic CONCLUSION: Till date, microemulsions have been
and bio-catalytic reactions are conducted in pure shown to be able to protect labile drug, control drug
organic or aqua-organic media. Biphasic media are release, increase drug solubility, increase
also used for these types of reactions. The use of pure bioavailability and reduce patient variability.
apolar media causes the denaturation of biocatalysts. Furthermore, it has proven possible to formulate
The use of water-proof media is relatively preparations suitable for most routes of
advantageous. Enzymes in low water content display administration. There is still however a considerable
and have; amount of fundamental work characterizing the
physico-chemical behavior of microemulsions that
1. Increased solubility in non-polar reactants needs to be performed before they can live up to their
2. Possibility of shifting thermodynamic potential as multipurpose drug delivery vehicles.
equilibrium in favor of condensations
3. Improvement of thermal stability of the Recently, several research papers have been published
enzymes, enabling reactions to be carried out for the improvement of drug delivery, but still there is
at higher temperatures. a need to put an emphasis on its characterization part
including in vitro evaluation. Besides this, research
Many enzymes, including lipases, esterases, papers shows higher percentage of surfactant (much
dehydrogenases and oxidases often function in the higher than CMC level) used for the formation of
cells in microenvironments that are hydrophobic in microemulsion, irrespective of different routes of
nature. In biological systems many enzymes operate administration, but there is a lack of toxicological
at the interface between hydrophobic and hydrophilic evaluation of the prepared microemulsion, which can
domains and these usually interfaces are stabilized by be a broad research area in future.
polar lipids and other natural amphiphiles. Enzymatic
catalysis in microemulsions has been used for a variety ACKNOWLEDGEMENTS: Authors thank the Director,
of reactions, such as synthesis of esters, peptides and Dehradun Institute of Technology, Dehradun, for
sugar acetals transesterification; various hydrolysis providing me with the necessary guidance for this
reactions and steroid transformation. The most widely work.
used class of enzymes in microemulsion-based
reactions is of lipases 57. Declaration of Interest section: None

Other Applications: REFERENCES:

1. Danielsson I, Lindman B: The definition of microemulsion. Colloid
1. Microemulsions can improve skin penetration of Surf 1981; 3: 391-392.
lycopene. 2. Narang AS, Delmarre D, Gao D: Stable drug encapsulation in
2. Microemulsion as a vehicle for transdermal micelles and microemulsions. Int J Pharm 2007; 345: 9-25.
3. Yuan Y, Li S-M, Mo F-K, D-F Zhong: Investigation of microemulsion
permeation of nimesulide system for transdermal delivery of meloxicam. Int J Pharm 2006;
3. Microemulsion in enhanced oil recovery, 321: 117-123.
detergency, cosmetics, agrochemicals, food. 4. Ktistis, G., Niopas, I., 1998: A study on the in-vitro percutaneous
absorption of propranolol from disperse systems. J. Pharm.
Microemulsions in environmental remediation and Pharmacol. 50, 413–418.
detoxification. 5. Kreilgaard, M., Pedersen, E.J., Jaroszewski, J.W: NMR
4. Microemulsions as fuels, as lubricants, cutting oils characterization and transdermal drug delivery potential of
microemulsion systems. J. Control. Release 69, 421–433.
and corrosion inhibitors, coatings and textile 6. Gasco, M.R., Gallarate, M., Pattarino, F., 1991: In vitro
finishing. permeation of azelaic acid from viscosized microemulsions. Int. J.
5. Microemulsions in microporous media synthesis Pharm. 69, 193–196.
7. Kriwet, K., Müller-Goymann, C.C: Diclofenac release from
(microemulsion gel technique) Microemulsions in phospholipid drug systems and permeation through excised
analytical applications. human stratum corneum. Int. J. Pharm. 125, 231–242.
6. Microemulsions as liquid/membranes Novel 8. Trotta, M: Influence of phase transformation on indomethacin
release from microemulsions. J. Control. Release 60, 399–405.
crystalline colloidal arrays as chemical sensor
materials 58.

Available online on www.ijpsr.com 1897

 Madhav and Gupta, IJPSR, 2011; Vol. 2(8): 1888-1899 ISSN: 0975-8232

9. Alvarez-Figueroa, M.J., Blanco-Méndez, J: Transdermal delivery of 32. Betageri, G., Prabhu, S: Semisolid preparations In Encyclopaedia
methotrexate: iontophoretic delivery from hydrogels and passive of Pharmaceutical Technology, Second Edition; Ed: Swarbrick, J.,
delivery from microemulsions. Int. J. Pharm. 215, 57–65. Boylan, J.C.; Marcel Dekker, Inc., New York, 2002, Vol-3; 2441 –
10. Pershing, L.K., Lambert, L.D., Knutson, K: Mechanism of ethanol- 2442.
enhanced estradiol permeation across human skin in vivo. Pharm. 33. Ghosh, P.K., Murthy, R.S.R: Microemulsions: A Potential Drug
Res. 7, 170–175. Delivery System, C. Drug. Del., 2006, 3; 167-180.
11. Liu, P., Kurihara-Bergstrom, T., Good, W.R: Cotransport of 34. Hoar, T.P., Schulman, J.H: Transparent water-in-oil dispersions:
estradiol and ethanol through human skin in vitro: understanding the oleopathic hydro-micelle, Nature, 1943, 152; 102-103.
the permeant/enhancer flux relationship. Pharm. Res. 8, 938– 35. Carlfors, J.,Blute, I. , Schmidt, V: Lidocaine in microemulsion — a
944. dermal delivery system, J. Disp. Sci. Technol. 12, 467–482.
12. Kim, Y.-H., Ghanem, A.-H., Mahmoud, H., Higuchi, W.I: Short 36. Israelachvilli, J.N., Mitchell, D.J., Ninham, B.W: Theory of self
chain alkanols as transport enhancers for lipophilic and assembly of hydrocarbon amphiphiles into micelles and bilayers,
polar/ionic permeants in hairless mouse skin: mechanism(s) of J. Chem. Soc. Faraday Trans. II 72, 1525–1567.
action. Int. J. Pharm. 80, 17–31. 37. Mitchell, D.J., Ninham, B.W: Micelles, vesicles and
13. Pershing, L.K., Parry, G.E., Lambert, L.D: Disparity of in vitro and microemulsions, J. Chem. Soc. Faraday. Trans. II 77, 601–629.
in vivo oleic acid-enhanced b-estradiol percutaneous absorption 38. Attwood, D., Mallon, C., Taylor, C.J: Phase studies of oil-in water
across human skin. Pharm. Res. 10, 1745– 1750. phospholipid microemulsions, Int. J. Pharm. 84, R5–R8.
14. Tanojo, H., Junginger, H.E., Boddé, H.E: In vivo human skin 39. Aboofazeli, R., Lawrence, C.B., Wicks, S.R., Lawrence, M.J:
permeability enhancement by oleic acid: transepidermal water Investigations into the formation and characterisation of
loss and Fourier-transform infrared spectroscopy studies. J. phospholipid microemulsions. III. Pseudo-ternary phase diagrams
Control. Release 47, 31–39. of systems containing water–lecithin–isopropyl myristate and
15. Hadgraft, J: Skin, the final frontier. Int. J. Pharm. 224, 1–18. either an alkanoic acid, amine, alkanediol, polyethylene glycol
16. Goldberg-Cettina, M., Liu, P., Nightingale, J., Kurihara-Bergstrom, alkyl ether or alcohol as cosurfactant, Int. J. Pharm. 111, 63–72.
T: Enhanced transdermal delivery of estradiol in vitro using binary 40. Aboofazeli, R., Lawrence, M. J: Investigations into the formation
vehicles of isopropyl myristate and short-chain alkanols. Int. J. and characterization of phospholipid microemulsions: I Pseudo-
Pharm. 114, 237–245. ternary phase diagrams of systems containing water–lecithin–
17. Fang, J.-Y., Yu, S.-Y., Wu, P.-C., Huang, Y.-B., Tsai, Y.-H: In vitro alcohol–isopropyl myristate, Int. J. Pharm. 93, 161–175.
skin permeation of estradiol from various proniosome 41. Shinoda, K., Araki, M., Sadaghiani, A., Khan, A., Lindman, B:
formulations. Int. J. Pharm. 215, 91–99. Lecithin-Based Microemulsions: Phase Behaviour and Micro-
18. Acharya, S. P., Moulik, S. K. Sanyal, Mishra, B. K. and Puri, P. M: Structure, J. Phys. Chem. 95, 989–93.
Physicochemical Investigations of Microemulsification of Coconut 42. Angelo, M.D., Fioretto, D., Onori, G., Palmieri, L., Santucvelocity,
Oil and Water Using Polyoxyethylene 2-Cetyl Ether (Brij 52) and A: Dynamics of water-containing sodium bis(2-ethylhex-
Isopropanol or Ethanol, Journal of Colloid and Interface Science yl)sulfosuccinate (AOT) reverse micelles: a high-frequency
245 , 163–170. dielectric study, Phys. Rev. E 54, 993–996.
19. Winsor, P. A. Trans. Faraday Soc. 1948, 44, 376. 43. Bhargava, H.N., Narurkar, A., Lieb, L. M: Using microemulsions for
20. Schulman, J. H.; Stoeckenius, W.; Prince, M. J. Phys. Chem. 1959, drug delivery, Pharm. Tech. 11, 46–52.
63, 1677. 44. Attwood: Microemulsions, in: J. Kreuter (Ed.), Colloidal Drug
21. Friberg, S. E.; Mandell, L.; Larsson, M. J: Colloid Interface Sci. Delivery Systems, Dekker , New York , 31–71.
1969, 29, 155. 45. Eccleston: Microemulsions, in: J. Swarbrick, J.C. Boylan (Eds.),
22. Adamson, A. W. J: Colloid Interface Sci. 1969, 29, 261. Encyclopedia of Pharmaceutical Technology, Vol. 9, Marcel
23. Prince, L. M: Microemulsions, Theory and Practice; Prince, L. M., Dekker, New York, 375–421.
Ed.; Academic Press: New York, 1977. 46. Lawrence, M.J: Surfactant systems: microemulsions and vesicles
24. Tadros, Th. F.; Vincent, B: Encyclopaedia of Emulsion Technology; as vehicles for drug delivery, Eur. J. Drug Metab. Pharmacokinet.
Becher, P., Ed.; Vol 1; Marcel Dekker: New York, 1980. 3, 257-269.
25. Hunter, R. J: Introduction to Modern Colloid Science; 1st ed.; 47. Lawrence, M.J: Microemulsions as drug delivery vehicles, Curr.
Oxford University Press: Oxford, 1994. Opin. Colloid Interface Sci. 1, 826–832.
26. Martin, A: Coarse Dispersions In Physical Pharmacy, Fourth 48. Vyas, S.P., Khar, R.K: Submicron emulsions in targeted and
Edition; B.I. Waverly Pvt. Ltd., New Delhi, 1994; 495 – 496. controlled drug delivery, Novel Carrier Systems; CBS Publishers
27. Shaji, J., Reddy, M.S: Microemulsions as drug delivery systems, and Distributors, New Delhi, 2002; 282 – 302.
Pharma Times, 2004, 36 (7); 17 – 24. 49. Prapaporn Boonme et al., Mahidol University, Bangkok:
28. Kayes, F.B: Disperse systems In Pharmaceutics: The Science of Characterization of Microemulsion Structures in the
Dosage Form Design, International Student Edition; Ed: Aulton, Pseudoternary Phase Diagram of Isopropyl Palmitate/Water/Brij
M.E.; Churchill Livingstone, 1999; 110. 97:1-Butanol. Published: May 12, 2006
29. Rieger, M.M: Emulsions In Theory and Practice of Industrial 50. Corswant, V.C., Thoren, P., Engstrom, S: Triglyceride – based
Pharmacy, Third Edition; Ed: Lachman, L., Lieberman, H.A., Kanig, microemulsion by Intravenous administration of sparingly soluble
J.L.; Varghese Publishing House, Bombay, 1987; 507 – 519. substances, J .Pharm. Sci., 1998, 87 (2); 200.
30. Emsap, W.J., Siepmann, J., Paeratakul, O: Disperse Systems In 51. Ho, H.O., Hsiao, C.C., Sheu, M.T: Preparation of Microemulsions
Modern Pharmaceutics, Fourth Edition; Ed: Banker, G.S., Rhodes, Using Polyglyceryl Fatty acid Esters as Surfactant for the Delivery
C.T.; Marcel Dekker, Inc., New York, 2002, Vol-121; 260 – 261. of Protein Drugs, J.Pharm Sci, 1996, 85 (2) ; 138.
31. Eccleston, G.M: Emulsion and Microemulsions In Encyclopedia of 52. Kovarik, J.M., Muller, E.A., Van Bree, J.B., Tetzioff, W., Kutz, K:
Pharmaceutical Technology, Second Edition; Ed: Swarbrick, J., Reduced Inter and Intra Individual Variability in Cyclosporin
Boylan, J.C.; Marcel Dekker, Inc., New York, 2002, Vol-2; 1080 – Pharmacokinetics From Microemulsion Formulation, J. Pharm.
1085. Sci., 1994, 83 (3); 444.

Available online on www.ijpsr.com 1898

 Madhav and Gupta, IJPSR, 2011; Vol. 2(8): 1888-1899 ISSN: 0975-8232

53. Ho, H.O., Huang, M.C., Chen, L.C., Hsia, A., Chen, K.T., Chiang, 56. Hasse, A., Keipert, S: Development and characterisation of
H.S., Spur, B.W., Wong, P.Y.K., Sheu, M.Y: The percutaneous microemulsions for ocular application, Eur. J. Pharm. Biopharm.,
delivery of prostaglandin E1 and its alkyl esters by 1997, 43; - 179–183.
microemulsions, Chin. Pharm. J., 1998, 50; 257–266. 57. Malmsten, M: Microemulsions in pharmaceuticals In Handbook
54. Schmalfun,U., Neubert, R., Wohlrab, W: Modification of drug of Microemulsion, Science and Technology; Ed : Kumar, P., Mittal,
penetration into human skin using microemulsions, J. Control. K.L.; Marcel Dekker, Inc., New York, 1999; 755 – 771.
Rel., 1997, 46; 279–285. 58. Paul, B.K., Moulik, S.P: Uses and Applications of Microemulsions,
55. Dreher, F., Walde, P., Walther, P., Wehrli, E: Interaction of a Current Science, 2001, 80 (8); 990 – 1001.
lecithin microemulsion gel with human stratum corneum and its
effect on transdermal transport, J. Control. Rel., 1997, 45; 131–
140.

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