Journal of Scientific and Innovative Research 2014; 3(4): 467-474

Available online at: www.jsirjournal.com

Review Article Microemulsions: As drug delivery system

ISSN 2320-4818
JSIR 2014; 3(4): 467-474 Amul Mishra*, Ridhi Panola, A.C. Rana
© 2014, All rights reserved
Received: 18-06-2014 Abstract
Accepted: 15-08-2014
Microemulsions are excellent candidates as potential drug delivery systems because of their
improved drug solubilization, long shelf life, and ease of preparation and administration. The
Dr. Amul Mishra formulation of microemulsion for pharmaceutical use requires a thorough understanding of the
Department of Pharmaceutics, B.N.
Institute of Pharmaceutical properties, uses, and limitations of microemulsion. Three distinct microemulsions – oil external,
Sciences, Udaipur-313002, water external and middle phase can be used for drug delivery, depending upon the type of drug
Rajasthan, India delivery upon the type of drug and the site of action. In this article, Since the term
Ridhi Panola ‘microemulsion’ was first coined almost fifty years ago to describe clear, isotropic,
Department of Pharmaceutics, B.N. thermodynamically stable systems composed of oil, water, surfactant and cosurfactant,
Institute of Pharmaceutical numerous and varied reports of the applications of microemulsions have appeared in the
Sciences, Udaipur-313002,
Rajasthan, India literature. Reports of the use of microemulsions in separation science began to appear in the
literature in the early 1990’s when they were first used as mobile phases for HPLC and as
Dr. A.C. Rana carrier electrolytes for CE separations, particularly for pharmaceutical applications.
Director, Institute of Pharmacy,
Krukshetra University, Krukshetra-
136119, Haryana, India Keywords: Micelle, Thermodynamics, Co-solvents, Transparent, Coarse.

Introduction
The term “microemulsion” refers to a thermodynamically stable isotropically clear
dispersion of two immiscible liquids, such as oil and water, stabilized by an interfacial
film of surfactant molecules. A microemulsion is considered to be a
thermodynamically or kinetically stable liquid dispersion of an oil phase and a water
phase, in combination with a surfactant. The dispersed phase typically comprises small
particles or droplets, with a size range of 5 nm-200 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. The microemulsion is formed readily and
sometimes spontaneously, generally without high-energy input. In many cases a
cosurfactant or cosolvent is used in addition to the surfactant, the oil phase and the
water phase.

Three types of microemulsions are most likely to be formed depending on the

composition:
Correspondence:
Dr. Amul Mishra  Oil in water microemulsions wherein oil droplets are dispersed in the continuos
Department of Pharmaceutics, B.N. aqueous phase
Institute of Pharmaceutical
Sciences, Udaipur-313002,  Water in oil microemulsions wherein water droplets are dispersed in the
Rajasthan, India continuous oil phase;
Tel: +91 9414738107  Bi-continuous microemulsions wherein microdomains of oil and water are
E-mail:
[email protected]
interdispersed within the system.

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In all three types of microemulsions, the interface is The droplet size in the dispersed phase is very small,
stabilized by an appropriate combination of surfactants usually below 140 nm in diameter, which makes the
and/or co-surfactants. microemulsions transparent liquids.3 In principle,
microemulsions can be used to deliver drugs to the patients
History via several routes, but the topical application of
The concept of microemulsion was first introduced by microemulsions has gained increasing interest.
Hoar and Schulman in 1943; they prepared the first A unique attempt was made4 to emulsify coconut oil with
microemulsions by dispersing oil in an aqueous surfactant the help of polyoxyethylene 2-cetyl ether (Brij 52) and
solution and adding an alcohol as a co-surfactant, leading isopropanol or ethanol, forming stable isotropic dispersion
to a transparent, stable formulation.1 thus paving way for use of plant and vegetable oil to be
The existence of this theoretical structure was later used as oil phase in microemulsion.
confirmed by use of various technologies, and we can The surfactants used to stabilise such systems may be:
today adopt the definition given by Attwood: “a
microemulsion is a system of water, oil, and amphiphilic (i) Non-ionic
compounds (surfactant and co-surfactant) which is a (ii) Zwitterionic
transparent, single optically isotropic, and (iii) Cationic
thermodynamically stable liquid”. 2
(iv) Anionic surfactants

Objectives A combinations of these, particularly ionic and non-ionic,

can be very effective at increasing the extent of the
The overall objective of this thesis was to develop stable microemulsion region.
salt-containing w/o microemulsions for possible release
applications. The specific objectives were: i. Non-ionics include polyoxyethylene surfactants such as
Brij 35 (C12E35 ) or a sugar esters such as sorbitan
1. To prepare and optimise w/o microemulsions using monooleate (Span 80). Phospholipids are a notable.
combinations of surfactants, organic and aqueous phases
and to characterise the resulting microemulsions along two ii. Zwitterionic surfactants and exhibit excellent
dilution lines within the monophasic region in ternary biocompatibility. Lecithin preparations from a variety of
phase diagrams. sources including soybean and egg are available
commercially and contain diacylphosphatidylcholine as its
2. To incorporate a model hydrophilic guest molecule major constituent.5-8
(sodium chloride) into the water domains of oil-continuous
microemulsions and to characterise these salt containing iii. Cationic surfactants: Quaternary ammonium alkyl salts
microemulsions along the two dilution lines within the form with hexadecyltrimethyl ammonium bromide
monophasic region in the developed ternary phase (CTAB), and the twin-tailed surfactant
diagrams. didodcecylammonium bromide (DDAB) are amongst the
most well known.
3. To test the efficiency of selected salt-containing
microemulsion compositions for salt-release using iv. Anionic surfactan: The most widely studied is probably
conductivity and establish the mechanism of release. sodium bis-2-ethylhexylsulphosuccinate (AOT) which is
twin-tailed and is a particularly effective stabiliser of w/o
Formulation microemulsions.9
Microemulsions are colloidal dispersions composed of an Attempts have been made to rationalise surfactant
oil phase, aqueous phase, surfactant and cosurfactant at behaviour in terms of the hydrophile–lipophile balance
appropriate ratios. (HLB) 10, as well as the critical packing parameter
Unlike coarse emulsions micronized with external energy (CPP).11,12 Both approaches are fairly empirical but can be
microemulsions are based on low interfacial tension. This a useful guide to surfactant selection. The HLB takes into
is achieved by adding a cosurfactant, which leads to account the relative contribution of hydrophilic and
hydrophobic fragments of the surfactant molecule. It is
spontaneous formation of a thermodynamically stable
microemulsion. generally accepted that low HLB (3–6) surfactants are

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favoured for the formation of w/o microemulsions whereas at slow rate with gradual stirring until the system is
surfactants with high HLBs (8–18) are preferred for the transparent. The amount of surfactant and cosurfactant to
formation of o/w microemulsion systems. Ionic surfactants be added and the percent of oil phase that can be
such as sodium dodecyl sulphate which have HLBs greater incorporated shall be determined with the help of pseudo-
than 20, often require the presence of a cosurfactant to ternary phase diagram. Ultrasonicator can finally be used
reduce their effective HLB to a value within the range so to achieve the desired size range for dispersed globules.
required for microemulsion formation. In contrast, the CPP It is then be allowed to equilibrate.
relates the ability of surfactant to form particular
aggregates to the geometry of the molecule itself. Gel may be prepared by adding a gelling agent to the
above microemulsion. Carbomers (crosslinked polyacrylic
In most cases, single-chain surfactants alone are unable to acid polymers) are the most widely used gelling agent.
reduce the oil /water interfacial tension sufficiently to
enable a microemulsion to form, a point made in a number Construction of Phase Diagram
of pertinent microemulsions reviews.13-17 Medium chain Pseudo-ternary phase diagrams of oil, water, and co-
length alcohols which are commonly added as
surfactant/surfactants mixtures are constructed at fixed
cosurfactants, have the effect of further reducing the cosurfactant/surfactant weight ratios. Phase diagrams are
interfacial tension, whilst increasing the fluidity of the obtained by mixing of the ingredients, which shall be pre-
interface thereby increasing the entropy of the system.14, 15 weighed into glass vials and titrated with water and stirred
Medium chain length alcohols also increase the mobility of well at room temperature. Formation of monophasic/
the hydrocarbon tail and also allow greater penetration of
biphasic system is confirmed by visual inspection. In case
the oil into this region. turbidity appears followed by a phase separation, the
Various pharmaceutically acceptable excipients available samples shall be considered as biphasic. In case
that can be used in microemulsion formulation are: monophasic, clear and transparent mixtures are visualized
after stirring, the samples shall be marked as points in the
Long chain or high molecular weight (>1000) surfactants phase diagram. The area covered by these points is
include: considered as the microemulsion region of existence.

Gelatin, casein, lecithin (phosphatides), gum acacia,

cholesterol, tragacanth, polyoxyethylene alkyl ethers, e.g.,
macrogol ethers such as cetomacrogol 1000,
polyoxyethylene castor oil derivatives, polyoxyethylene
sorbitan fatty acid esters, e.g., the commercially available
Tweens, polyethylene glycols, polyoxyethylene stearates,
colloidal silicon dioxide, phosphates, sodium
dodecylsulfate, carboxymethylcellulose calcium,
carboxymethylcellulose sodium, methylcellulose,
hydroxyethylcellulose, hydroxypropylcellulose,
hydroxypropylmethylcellulose phthalate, microcrystalline
cellulose, magnesium aluminum silicate, triethanolamine,
polyvinyl alcohol, and polyvinylpyrrolidene (PVP).
Figure 1: Hypothetical phase regions of microemulsion system
The low molecular weight (<1000) surfactants include of oil (O), water (W), and surfactant + cosurfactant (S)
Stearic acid, benzalkonium chloride, calcium stearate,
glycerol monostearate, cetostearyl alcohol, cetomacrogol
emulsifying wax, and sorbitan esters. Characterization of Microemulsion

Preparation of Microemulsion The droplet size, viscosity, density, turbidity, refractive

index, phase separation and pH measurements shall be
The drug is be dissolved in the lipophilic part of the performed to characterize the microemulsion.
microemulsion i.e. Oil and the water phases can be
combined with surfactant and a cosurfactant is then added

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The droplet size distribution of microemulsion vesicles can  Various routes like tropical, oral and intravenous
be determined by either light scattering technique or can be used to deliver the product
electron microscopy. This technique has been advocated as  Rapid and efficient penetration of the drug moiety
the best method for predicting microemulsion stability.  Helpful in taste masking
 Provides protection from hydrolysis and oxidation
Advantages of Microemulsion over other dosage forms: as drug in oil phase in O/W microemulsion is not
 Increase the rate of absorption exposed to attack by water and air.
 Eliminates variability in absorption  Liquid dosage form increases patient compliance.
 Helps solublize lipophilic drug  Less amount of energy requirement.
 Provides a aqueous dosage form for water The key difference between emulsions and
insoluble drugs microemulsions18
 Increases bioavailability

Table 1: Key difference between emulsions and microemulsions

1. Emulsions consist of roughly spherical droplets of 1. They constantly evolve between various structures
one phase dispersed into the other. ranging from droplet like swollen micelles to
bicontinuous structure.

2.Droplet diameter: 1 – 20 mm. 2.10 – 100 nm.

3. Most emulsions are opaque (white) because bulk of 3. Microemulsions are transparent or translucent as
their droplets is greater than wavelength of light and their droplet diameter are less than ¼ of the
most oils have higher refractive indices than water. wavelength of light, they scatter little light.

4 .Ordinary emulsion droplets, however small exist 4. Microemulsion droplet may disappear within a
as individual entities until coalesance or Ostwald fraction of a second whilst another droplet forms
ripening occurs. spontaneously elsewhere in the system.

5. They may remain stable for long periods of time, 5. More thermodynamically stable than macro
will ultimately undergo phase separation on standing emulsions and can have essentially infinite lifetime
to attain a minimum in free energy. They are assuming no change in composition, temperature and
kinetically stable thermodynamically unstable. pressure, and do not tend to separate.
6. They are lyophobic. 6. They are on the borderline between lyophobic and
lyophilic colloids.
7. Require intense agitation for their formation. 7. Generally obtained by gentle mixing of
ingredients.

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Microemulsion as drug carrier system and method of Topical drug delivery Microemulsions may enhance
drug delivery system transdermal drug delivery primarily by the following
effects: Micro emulsions can exhibit a high solubilization
Microemulsion as drug carrier system capacity for both lipophilic and hydrophilic drugs, thus
Some of the important properties of microemulsions are more drug can be loaded into the microemulsion, which
that they improve therapeutic efficacy of the drug and increases the concentration gradient across the skin
allow reduction in the volume of the drug delivery vehicle, without depletion. The reservoir effect of the internal
thus minimizing toxic side effects. The presence of phase maintains a constant driving force of drug from the
surfactant raises the permeability of the cell membrane, external phase to the skin and prolongs absorption. Since
which allows for easier absorption. In some cases, the the diffusion of the drug into the skin only occurs from the
capacity of the cell membrane to solubilize large amounts external phase of the micro emulsion, the internal phase
of lipophilic drugs at the same time can be advantages as continually supplies drug to the external phase so that it
well. remains saturated with the drug.21

In addition to these advantages, microemulsions are Applications of Topical Microemulsions

expected to be administering to children and adults who Microemulsions are promising delivery systems that allow
have difficulty swallowing solid doses forms. They also sustained or controlled drug release for percutaneous,
offer several benefits for oral administration, including peroral, topical, and transdermal, administration. Enhanced
increased absorption, improved clinical potency, and absorption of drugs, modulation of the kinetics of the drug
decreased toxicity. Therefore, microemulsions have been release and decreased toxicity are several advantages in the
reported to be ideal for oral delivery of drugs such as delivery process.
steroids, hormones, diuretics, and antibiotics.
The following is a application of topical micro emulsions.-
Some factors limit the use of microemulsion in
pharmaceutical applications. The need for Antifungal
pharmaceutically acceptable ingredients limits the choice
of microemulsion components (e.g., oil, surfactant, and Superficial mycoses usually respond to topical therapy. In
cosurfactant), leading to difficulties in formation.19 the Settling of eczema, topical antifungal agents such as
ketoconazole are used to reduce the fungal infection
Method of drug delivery system caused by Pityrosporum ovale or Malassezia furfur.
The use of microemulsions as drug delivery vehicle has
been an exciting and attractive area of research because of Antifungal agents e.g miconazole, ketoconazole, and
its many potential and extraordinary benefits. itraconazole being lipophilic in nature have been
Microemulsions offer an interesting and potentially quite formulated as microemulsions to impart to them the
powerful alternative carrier system for drug delivery advantages like ease of preparation due to spontaneous
because of their high solubilization capacity, transparency, formation, thermodynamic stability, transparent and
thermodynamic stability, ease of preparation, and high elegant appearance, increased drug loading, enhanced
diffusion and absorption rates when compared to solvent penetration through the biological membranes, increased
without the surfactant system. The oral efficacy of bioavailability compared between conventional dosage
microemulsion has already been proved by cyclosporine forms. .
formulation (Neoral), but apart from oral route, Antiviral
microemulsions for other routes like dermal, transdermal,
ocular, vaginal, rectal, buccal, periodontal, parenteral, and A study was done to investigate and evaluate
nasal delivery routes have also been developed. The microemulsion and microemulsion-based hydrogel as a
present review focuses on various applications of topical delivery system for penciclovir in comparison with
microemulsions through different above mentioned routes a commercial cream.
and also gives idea about new application of micro
emulsion as oral solid dosage form, as microreactors and Acyclovir containing microemulsion-based formulations
as blood substitute.20 for topical delivery were developed using isopropyl
myristate/Captex 355/Labrafac as an oil phase, Tween 20
Topical drug delivery

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as surfactant , Span 20 as cosurfactant , and water Blinking, baseline and reflex lachrymation, and drainage
dimethylsulfoxide (1:3) as an aqueous phase. remove rapidly foreign substances, including drugs, from
the surface of the eye. Newer pharmaceutical ophthalmic
Anti acne formulation such as in-situ gel, nanoparticle, liposome,
Novel drug delivery strategies like microemulsions can nanosuspension, microemulsion, intophoresis and ocular
play a pivotal role in improving the topical delivery of inserts have been developed in last three decades increase
antiacne agents by enhancing their dermal localization the bioavailability of the drug as a sustained and controlled
with a 25 concomitant reduction in their side effects .Micro manner.23
emulsions of azelaic acid, a bioactive molecule used in Self emulsifying drug delivery system
many skin disorders, prepared using the monosodium salt
(AZA-Na) have been evaluated as delivery vehicles. Self emulsifying system has gained exposure of their
ability to increase solubility and bio availability of poorly
Antioxidants soluble drug. SEDDS are isotropic mixture of oil,
Antioxidants have been used in dermatological and surfactant and co-solvent. SEDDS produce fine oil in
cosmetic products because of their property of scavenging water emulsion when introduced in aqueous media under
and destroying aggressive oxidizing agents and free gentle agitation.
radicals that are involved in various skin conditions. There are two type of SELF system:
In animals, topical application of alpha-tocopherol has Self emulsifying drug delivery system [SEDDS]
shown to exert photoprotective effects by reducing the
number of sunburn cells; UV B induced damage and Self micro-emulsifying drug delivery system [SMEDDS]24
inhibiting photocarcinogenesis. An o/w or w/o
microemulsion of vitamin E delivered the vitamin Parenteral drug delivery
predominantly to the epidermis avoiding accumulation in
Parenteral Drug Delivery Parenteral administration
organs other than the skin. The cream or lotion (especially via the intravenous route) of drugs with limited
preparations of the same amount of vitamin results in solubility is a major problem extremely low amount of
excessive accumulation in the organs.22 drug actually delivered to a targeted site. Microemulsion
Ocular drug delivery formulations have distinct advantages over macro
emulsion systems when delivered parenterally because of
“Ophthalmic drug delivery is one of the most interesting the fine particle micro emulsion is cleared more slowly
and challenging endeavours facing the pharmaceutical than the coarse particle emulsion and, therefore, have a
scientist. The anatomy, physiology and biochemistry of the longer residence time in the body. Both O/W and W/O
eye render this organ exquisitely impervious to foreign micro emulsion can be used for Parenteral delivery.
substances. The challenge to the formulator is to
circumvent the protective barriers of the eye without O/W as the carrier for lipophilic drug -IV, IM and SC. o/w
causing permanent tissue damage. The primitive emulsion as a vector for FC, Ca antagonist, steroids. The
ophthalmic solutions, suspensions and ointment dosage targeting potential of O/W ME containing lipophilic drug
forms are clearly no longer sufficient to combat some to RE system. Higher PC better will target of drug. W/O
present virulent diseases.” Eye is a unique and very ME –hydrophilic drug prolong the release of drug by SC
valuable organ. This is considered a window hinge. We and IM.25
can enjoy it and look at the world body. There are many Research work on microemulsions
eye diseases that can affect the body and loss of vision as
well. Therefore, many eyes in drug delivery systems are During the last one decay much research work has been
available. They are classified as traditional and new drug done on microemulsions for various routes of drug
development system. Topical application of drugs to the administration. Due to their unique properties namely,
eye is the most popular and well-accepted route of ultraflow interfacial tension, large interfacial area,
administration for the treatment of various eye disorders. thermodynamic stability and the ability to solubilize
The bioavailability of ophthalmic drugs is, however, very otherwise immiscible liquids. Research work on
poor due to efficient protective mechanisms of the eye. microemulsions is summarized in Table 2.26

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Table 2: Research Work carried out on Microemulsions

Drug Name Route Purpose/Result

Flurbiprofen Parenteral Increased the solubility
Apormorphine HCL Transdermal Increased the permeability
Ketoprofen Transdermal Enhancement of permeability
Prilocainne-HCL Transdermal Increased the solubility
Estradiol Transdermal Improvement in solubilization
Aceclofenac Dermatological Increased the solubility
Piroxicam Oral Increased the solubility
Diclofenac Transdermal Permeability enhancement
Dexamethasone Topical Ocular Enhanced the Bioavailability
Chloramphenicol Ocular Increased the solubility
Ibuprofen Parenteral Increased the solubility
Sumatriptan Intranasal Enhanced the Bioavailability
Ibuprofen Topical Increasing the solubility
Doxorubicin - Increasing the Stability
Itraconazole Parenteral For better absorption
Timolol Ophthalmic For better absorption
Terbinafine Transdermal Permeability enhancement
Fenofibrate Self-Micro emulsifying Increasing the solubility
Progesterone Dermal Increased the chemical Stability

Conclusion to get onto the market than the first liposomal drug
delivery system.
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