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Review Article
Pranjal Kumar Singh1*, Mohd. Kashif Iqubal2, Vikesh Kumar Shukla3, Mohd. Shuaib4
1, 2, 4
Department of Pharmacy, Kalka Institute for Research and Advanced Studies, Meerut, Uttar Pradesh,
India
3
Department of Pharmacy, IIMT College of Medical Sciences, Meerut, Uttar Pradesh, India
ABSTRACT
Microemulsions are one of the best candidates as novel drug delivery system because of their long shelf life,
improved drug solubilization with ease of preparation and administration. Microemulsions are
thermodynamically stable and optically isotropic liquid solutions of oil, water and amphiphile. They have
emerged as novel vehicles for drug delivery which allow controlled or sustained release for ocular,
percutaneous, topical, transdermal, and parenteral administration of medicaments. Microemulsions can be
easily distinguished from normal emulsions by their low viscosity, transparency and more accurately their
thermodynamic stability. Microemulsions have great range of applications and uses such as in
pharmaceuticals, agrochemicals, cutting oils, biotechnology, food, cosmetics, analytical applications,
environmental detoxification etc. The main objective of this review paper is to discuss microemulsions as
drug carrier system with other possible applications.
The formulation and development of novel drug 1. Microemulsions are easily prepared and
delivery system with the nature of enhancing the require no energy contribution during
effectiveness of existing of drug is an ongoing preparation this is due to better
process in pharmaceutical research. Since there thermodynamic stability.
are many types of drug delivery systems that have 2. The formation of microemulsion is reversible.
been developed. The microemulsion concept was They may become unstable at low or high
introduced in 1940s by Hoar and Schulman who temperature but when the temperature
generated a clear single-phase solution by returns to the stability range, the
triturating a milky emulsion with hexanol [1]. They microemulsionreforms.
prepared the first microemulsion by dispersing oil 3. Microemulsions are thermodynamically stable
in an aqueous surfactants solution and adding an system and allows self-emulsification of the
alcohol as a co-surfactant, leading to transparent system.
stable formulation. Microemulsion is defined as 4. Microemulsions have low viscosity compared
microemulsion are clear, transparent, to emulsions.
thermodynamically stable dispersions of oil and 5. Microemulsions act as supersolvents for drug,
water, stabilized by an interfacial film of surfactant can solubilise both hydrophilic and lipophilic
frequently in combination with a co-surfactant drugs including drugs that are insoluble in both
[2].Alternative names for these systems are often aqueous and hydrophobic solvents.
used, such as swollen micelle, 6. Having the ability to carry both lipophilic and
transparentemulsion, solubilized oil and micellar hydrophilic drugs.
solution. Microemulsions are bicontinuous 7. The dispersed phase, lipophilic or hydrophilic
systems that are essentially composed of bulk (O/W, or W/O microemulsions) can act as a
phases of water and oil separated by a potential reservoir of lipophilic or hydrophilic
surfactant/cosurfactant rich interfacial region [3]. drugs, respectively.
These systems have advantages over conventional 8. The use of microemulsion as delivery systems
emulsions in that they are thermodynamically can improve the efficacy of a drug, allowing the
stable liquid systems and are spontaneously total dose to be reduced and thus minimizing
formed [4]. Microemulsions are currently the side effects.
subject of many investigations because of their
Disadvantages of Microemulsion Systems [6-8]
wide range of potential and actual utilizations. The
high capacity of microemulsions for drugs makes
1. Having limited solubilizing capacity for high-
them attractive formulations for pharmaceuticals.
melting substances.
These systems also offer several benefits for oral
2. Require large amount of Surfactants for
administration, including increased absorption,
stabilizing droplets.
improved clinical potency and decreased toxicity
3. Microemulsion stability is influenced by
[5].
environmental parameters such as
temperature and pH.
1. They are lyophobic in nature. They are the border between lyophilic and
lyophobic.
2. Droplet diameter 1 to 20 mm. Droplet diameter 10 to 100 mm.
3. Macroemulsion droplets exist as individual Microemulsion droplets disappear within
entities. fraction of seconds.
4. Emulsion droplets are roughly spherical Microemulsions are the structures of various
droplets of one phase dispersed into the other droplets like bi-continous to swollen micelles.
phase.
5. Macroemulsions requires quick agitation for Microemulsions are obtained by gentle
their formation. mixing of ingredients.
6. Most of the emulsions are opaque (white) in Microemulsions are transparent or
appearance. translucent in nature.
Single phase homogeneous mixture or winsor IV molecules that contain a polar head group and a
polar tail. Surfactant molecules self-associate due
In single phase homogeneous mixture or winsor IV to various inter- and intra-molecular forces as well
the oil, water and surfactants are homogenously as entropy considerations. For example, when
mixed. surfactant is mixed with oil and water, they
accumulate at the oil/water interface, because it is
INGREDIENTS OF MICROEMULSION [18-20]
thermodynamically favorable. The surfactant
Various ingredients are used in the formulation molecules can arrange themselves in a variety of
and development of microemulsions. Mainly oil shapes. They can form spherical micelles, a
and surfactants are used in microemulsion they hexagonal phase, lamellar (sheet) phases,
should be biocompatible, non-toxic and clinically rodshaped micelles, reverse micelles, or hexagonal
acceptable. Main components of microemulsion reverse micelles. At low concentrations of
are dispersed (internal) phase, spherical, isolated
droplets are present in the microemulsions. The
1. Oil phase various types of surfactants that help in the
2. Aqueous phase progressive development of microemulsion
3. Surfactant system are
4. cosolvent
1. Cationic
Oil phase [21] 2. Anionic
Oil is one of the most important components of 3. Non-ionic
microemulsion because it can solubilise the 4. Zwitterionic surfactants.
required dose of the lipophilic drug and it
increases the fraction of lipophilic drug Cationic surfactant
transported via the intestinal lymphatic system. Cationic Surfactants when come in contact with
Oil is defined as any liquid having low polarity and water they come into amphiphiliccation and anion
low miscibility with water. The examples of such form, most often of halogen type. A very large
phase are cyclohexane, mineral oil, toulene, & quantity of this class corresponds to nitrogen
vegetable oil etc. compounds such as quaternary ammoniums and
fatty amine salts, with one or several long chain of
Aqueous phase the alkyl type, often coming from natural fatty
Generally the aqueous phase contains hydrophilic acids. The most well-known examples from the
active ingredients and preservatives. Sometimes cationic surfactant class are hexadecyl trimethyl-
Buffer solutions are used as aqueous phase. ammonium bromide and didodcecyl ammonium
bromide. These surfactants are in general more
Surfactant [22] expensive than anionics.
The term surfactant (surface-active-agent)
denotes a substance which exhibits some Anionic surfactant
superficial or interfacial activity & used to lower When anionic Surfactants are dissociated in water
the surface or interface tension. It has affinity for in an amphiphilic anion, and a cation, which is in
polar & nonpolar solvents. Surfactants are the general an alkaline metal (Na, K) or a quaternary
ammonium. These are the most commonly used flexible to take up different curvatures required to
surfactants. The anionic charge in these form microemulsion over a wide range of
surfactants comes from the ionized carboxyl excipients. If a single surfactant film is desired, the
group. Anionic surfactants account for about 50 % lipophilic chains of the surfactant should be
of the world production. Alkalialkanoates, also sufficiently short, or contain fluidizing groups (e.g.
known as soaps, are the most common anionic unsaturated bonds). Basic co-surfactants are short
surfactants. This is the most well-known type of chain alcohols (ethanol to butanol), glycols such as
surfactant when it comes to their shape and propylene glycol, medium chain alcohols, amines
function. The three most important anionic or acids. The use of co-surfactant is to destroy
groups in all of these surfactants are carboxylate, liquid crystalline or gel structures that come in
sulfonate and sulfate groups. place of a microemulsion phase.
cellophane membrane, containing the reasons, one of which is the avoidance of hepatic
microemulsion formulation and the plain drug first-pass metabolism, salivary and degradation of
solution, separately. At predetermined time the drug in stomach and related toxicity effects.
intervals samples were withdrawn from the Another is the direct delivery and targetability of
receptor compartment and analyzed for drug the drug to affected areas of the skin or eyes.
content, using a UV spectrophotometer at specific Now a day, there have been a number of studies
wavelength. in the area of drug penetration into the skin. They
are able to incorporate both hydrophilic (5-
APPLICATION OF MICROEMULSION SYSTEM flurouracil, apomorphine hydrochloride etc) and
lipophilic drugs (estradiol, finasteride,
Microemulsion in Pharmaceutical
ketoprofenetc) and enhance their permeation.
From last two decades there has been a revolution Since formation of microemulsion formation
in the utilization of microemulsion systems in a requires high surfactant concentration, the skin
variety of pharmaceuticals. irritation aspect must be considered especially
when they are intended to be applied for a longer
• Parenteral Delivery [45] period.
Parenteral administration (especially via the • Ocular and Pulmonary Delivery[48]
intravenous route) of drugs with limited solubility
is a major problem in industry because of the For the treatment of eye diseases, drugs are
extremely low amount of drug actually delivered essentially delivered topically. O/W
to a targeted site. Microemulsion formulations microemulsions have been investigated for ocular
have distinct advantages over macroemulsion administration, to dissolve poorly soluble drugs, to
systems when delivered parenterally because of increase absorption and to attain prolong release
the fine particle microemulsion is cleared more profile.
slowly than the coarse particle emulsion and,
Other pharmaceutical applications [49,50,51,52]
therefore, have a longer residence time in the
body. • Nasal delivery
• Oral Delivery [46] • Drug targeting
• Cellular targeting
Microemulsion formulations offer the several • Brain targeting
benefits over conventional oral formulation • Periodontal delivery
including increased absorption, improved clinical • Tumor targeting
potency, and decreased drug toxicity. Therefore,
microemulsions have been reported to be ideal Other application
delivery of drugs such as steroids, hormones,
• Microemulsions in analytical applications[53]
diuretic and antibiotics.
Microemulsions are widely used in the field of
• Topical delivery [47] analytical techniques such as chromatography etc.
In microemulsion electrokinetic chromatography
Topical administration of drugs can have (MEEKC), characterization of solute hydro -
advantages over other methods for several phobicity was carried out, which provides a quick
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