Current Opinion in Colloid & Interface Science 17 (2012) 306313

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Current Opinion in Colloid & Interface Science

journal homepage: www.elsevier.com/locate/cocis

Microemulsions as delivery systems

Monzer Fanun
Colloids and Surfaces Research Center, Al-Quds University, East Jerusalem, Palestine

a r t i c l e

i n f o

Article history:
Received 3 February 2012
Accepted 15 June 2012
Available online 30 June 2012

a b s t r a c t
Solubilization capacity, dissolution efciency, rate and extent of solute delivery are dependent on the microemulsion microstructure.
2012 Elsevier Ltd. All rights reserved.

Keywords:
Solubilization capacity
Dissolution rate
Generator of delivery systems
Delivery route
Delivery rate

1. Introduction
Microemulsions are transparent systems of two immiscible uids,
stabilized by an interfacial lm of surfactant or a mixture of surfactants, frequently in combination with a cosurfactant. These systems
could be classied as water-in-oil, bicontinuous or oil-in-water type
depending on their microstructure which is inuenced by their physicochemical properties and the extent of their ingredients [1,2]. Microemulsions are characterized by ultra low interfacial tension between
the immiscible phases and offer the advantage of spontaneous formation, thermodynamic stability, simplicity of manufacture, solubilization
capacity of lipophilic, hydrophilic and amphiphilic solutes, improved
solubilization and bioavailability of hydrophobic drugs, the large area
per volume ratio for mass transfer, and the potential for permeation enhancement. The development of delivery systems has had a huge impact on our ability to treat numerous diseases. To attain the highest
pharmacological effects with least side effects of drugs, drugs should
be delivered to target sites without signicant distribution to non-target
areas. Microemulsion systems have emerged as novel vehicles for drug
delivery which allow sustained or controlled release for transdermal, topical, oral, nasal, intravenous, ocular, parenteral and other administration
routes of drugs. Microemulsion drug delivery is a practical delivery platform for improving target specicity, therapeutic activity, and reducing
toxicity of drugs. Owing to the existence of different domains of variable
polarity in the microemulsion systems, they show an enormous potential
to be used as delivery vehicles for a diversity of drugs [1,2]. In this review
article, we have attempted to present a broad view over the past ve
years on microemulsions as solubilization and dissolution enhancers of

E-mail address: fanunm@gmail.com.

1359-0294/$ see front matter 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.cocis.2012.06.001

poorly soluble drugs, as a medium for generating new drug delivery systems and as delivery systems themselves.
2. Microemulsions as solubilization capacity enhancer and dissolution rate improver
In recent years microemulsions continued to be used as solubilization capacity enhancers and dissolution rate improvers for poorly soluble drugs. The works in this area focus on two aspects: rst, the
effect of different microemulsion structures on drug solubilization capacity and dissolution efciency and secondly, on the physicochemical characterization of drug loaded microemulsions compared to drug
free systems. Biocompatible microemulsions were used to solubilize
cephalexin. The drug solubilization capacity depends on the aqueous
phase content. Characterization of the volumetric and transport properties of the microemulsions revealed that the rigidity of the interface
was affected by the presence of the drug [3]. The microstructure of
microemulsion loaded with meloxicam was characterized. It was
found that the solubilization capability of microemulsion is strongly
interrelated with its microstructure [4]. Solubilization capacity and
dissolution efciency of glyburide (a very poorly-water-soluble hypoglycemic agent) were enhanced by the formulation of microemulsions
which consisted of a mixture of tween 20 and transcutol, 1:1, v/v, oil
(labrafac hydro) and water [5]. Monodisperse microemulsions solubilizing nadioxacin show promising results against Propionibacterium
acnes bacteria. Optimized formulations were characterized for surface
morphology by transmission electron microscopy and refractive index.
Flux of the optimized formulation was 2.24 times that of the control
[6]. Azithromycin loaded microemulsions were investigated at room
temperature by small-angle X-ray scattering (SAXS) technique. It was
found that the values of the effective interaction radius of the microemulsions are higher for the drug free compared to the drug loaded

M. Fanun / Current Opinion in Colloid & Interface Science 17 (2012) 306313

aggregates [7]. Microemulsions were used for the solubilization of ganoderma lucidum polysaccharides and triterpenes against transplant
tumor growth. The formulated systems signicantly inhibit the tumor
growth in Heps mice [8]. U-type microemulsions formulated with
water, mixed nonionic surfactants, and peppermint oil were used to solubilize celecoxib. Celecoxib solubilization capacity decreases with the increase in the water content. Microemulsion dilution and interfacial
factors contributing to the celecoxib solubilization were evaluated. Structural transitions occurring in the microemulsion region were elucidated
by electrical conductivity, dynamic viscosity, and small angle X-ray scattering measurements [9]. Celecoxib solubility enhancement of formulated microemulsions was apparent from a higher release rate as compared
to commercial product [10]. Enhanced diclofenac solubilization capacity
was observed in biocompatible microemulsions based on mixed nonionic surfactants and R(+)-limonene or isopropylmyristate. Solubilization
capacity of the drug was dependent on the oil type and microstructure
of the microemulsion [11]. Solubilized drug affected the points of structural transitions as revealed by small angle X-ray scattering measurements [12]. Diclofenac diethylamine (DDA) was also solubilized in
microemulsions and an analytical method was developed and validated
to evaluate its content [13]. Solubilization capacity of carbamazepine, an
antiepileptic drug, in U-type nonionic microemulsions was studied. Solubilization capacity of the drug was reliant on the microstructure of the
microemulsion and on the surfactant-to-oil phase weight ratio. The solubilization capacity in the concentrate (reversed micelles) was 15 folds
higher than its solubility in the oil. Being solubilized, carbamazepine
acts as a cosurfactant consequently it inuences the curvatures of the microstructures and as a result the boundaries of the structural regions and
the transition points between the different phases [14]. Self microemulsifying drug delivery system containing carbamazepine was also
formulated and evaluated as a possible alternative to traditional oral formulation. The study conrmed that these formulations improve carbamazepine solubility and dissolution rate [15]. Anionic microemulsions
containing antitumor drug doxorubicin were formulated and characterized. The results conrmed a correlation between the composition, the
structural features and drug delivery [16]. Self-microemulsifying drug
delivery system formulation has been developed for the solubilization
of poorly soluble drug nilvadipine [17]. Solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and microemulsions were
used solubilize querecetin. Microemulsions exhibited the highest capacity to load the drug, reaching a concentration around 1300 times higher
than its aqueous solubility. The release rate of querecetin was affected by
the properties of the microemulsions [18]. Microemulsions were
prepared and examined as a probable drug delivery system for an
antitubercular drug rifampicin. The microemulsion remained stable
following the inclusion of rifampicin. Dissolution studies conclude that
a controlled release of rifampicin is expected from oil-in-water droplet
[19]. New oil-in-water microemulsion was used for enhancing the loading capacity of an anti-inammatory drug piroxicam. It was found that
the piroxicam was contained in the interfacial lm of microemulsion systems more deeply in the palisade layer with ethanol as the cosurfactant
[20]. Numerous isoavone-enriched red clover extracts (RCE) were encapsulated into a phospholipid-based microemulsion system. The
results indicated that the encapsulated quantities of isoavones
in RCE-encapsulated microemulsions were increased by over 10-fold
when compared with that of the raw red clover extracts [21]. Solid
microemulsions were formulated for improved delivery of simvastatin.
Dissolution studies have shown remarkable increase in the dissolution
of the drug as compared to plain drug. All the formulations provided
signicant reduction in the total cholesterol levels in hyperlipidemic
rats with reference to rats of control group [22]. Micronization is for
the most part an efcient method to increase the dissolution rate of
poorly water-soluble drugs and bioavailability in human body. Microemulsion systems were applied to micronize mitotane and warfarin
by cooling method and solvent diffusion process. The particle size of
mitotane and warfarin re-crystallized from microemulsion systems

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were signicantly reduced (to 1 m) compared with that of the commercial ones. As a result, the dissolution rate coefcients of re-crystallized
mitotane and warfarin were considerably enhanced by, respectively, 7.5
and 13.3 times larger than those of the commercial ones [23]. Water-inoil microemulsion was formulated and used in the preparation of
cetirizine hydrochloride. Quality studies on these microemulsions show
that these systems could be a promising new carrier for hydrosoluble
drugs [24].
3. Microemulsions as generators of drug delivery systems
In recent years microemulsions were used to generate, formulate
and synthesize new drug delivery systems that include new tablets
type, microspheres, lipid nanocapsules, microparticles, silica coated
nanoparticles, gel nanoparticles, solid lipid nanoparticles, magnetic
nanoparticles and quantum dots. The inuence of hydroxyapatite
[Ca5(PO4)3OH, HAP] tablets generated via microemulsion after sintering
at 700 C on ibuprofen release proles revealed that controlling microemulsion concentration in tablets before sintering affects the drug release from the HAP tablets [25]. Coreshell structure adriamycin lipiodol
microemulsions (ADM-CSLMs) were prepared through the emulsication method and evaluated for their in vivo antitumor effects in
combination with diethyldithiocarbamate (DDC). Two types of
ADM-CSLMs, adriamycin liposome-lipiodol microemulsion (ADM-LLM)
and adriamycin microsphere lipiodol microemulsion (ADM-MLM) were
prepared. The drug loading and encapsulation efciency of ADM-CSLMs
were measured by the high-performance liquid chromatography
(HPLC). It was found that ADM-CSLMs are useful carriers for the
treatment of carcinoma and their anti-tumor effect can be enhanced
by DDC in a suitable concentration [26]. A new type of triangular
pyramid-shaped microparticles of puerarin and aspirin were prepared
on copper substrate by using oil-in-oil microemulsion method [27].
Radiolabelled and uorescent lipid nanocapsules (LNCs) were synthesized by using a phase inversion process that follows the formation of
an oil/water microemulsion. They are important to be considered toward the development of nanomedicines that use drugs sensitive to lysosomal degradation or that need to reach extra endo-lysosomal targets
[28]. Hyaluronic acid (HA) particles with positive and negative charges
on their surfaces were synthesized using an aqueous solution of linear
HA in a sodium bis (2-ethylhexyl) sulfosuccinate (AOT)-isooctane
microemulsion system. The prepared HA particles were post modied
and were found to be used as drug delivery vehicles for trimethoprim
and naproxen as model drugs [29]. Hydrophobic drug nanoparticles,
in a form of water dispersible powder were formulated by rapid conversion of nanodroplets into nanoparticles, by evaporation of all volatile
solvents from microemulsions containing a dissolved drug in the dispersed oil phase. Powders composed of either amorphous or crystalline
particles at the size range of 10100 nm were obtained [30]. A fully
water-dilutable biocompatible microemulsion system was used as a
template for the preparation of celecoxib nanoparticles obtained as
amorphous dry powder. As a result of the nanometric size and amorphous state, about 10-fold increase in dissolution of the powder was
obtained, compared to that for particulate celecoxib in the presence of
surfactants [31]. Celecoxib nanoparticles in powder were obtained by
immediate conversion of microemulsion droplets into nanoparticles
by spray drying [32]. Stable nanoparticles with inner spherical solid
spheres and an outer hydrogel matrix were prepared using a hot
oil-in-water hydrogel-thickened microemulsion. The in vitro skin permeation studies showed that the nanoparticles could considerably decrease the penetration of model drugs through skin and resulted in
their dermal uptakes in skin [33]. Oil-in-water microemulsions were
used for the preparation of nanoparticles of a poorly water-soluble
drug, simvastatin by solvent evaporation method. It was found that tablets containing the akes of simvastatin nanoparticles showed great enhancement in dissolution prole compared with conventional tablets
[34]. The entrapment of insulin in poly(alkylcyanoacrylate) nanoparticles

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M. Fanun / Current Opinion in Colloid & Interface Science 17 (2012) 306313

prepared from microemulsions with different microstructures was optimized. The study demonstrated a strategy of delivering insulin orally
[35]. Poly(ethylcyanoacrylate) nanoparticles to be used as drug delivery
systems were prepared by interfacial polymerization on the basis of
microemulsions [36]. Microemulsion method was used to prepare Rhodamine B isothiocyanate doped silica-coated (RBITC-SiO2) nanoparticles
that were conjugated with Fe(III) complex of di(picolyl)amine to produce
nal nanosphere (RBITC-SiO2@dpa-Fe). The conjugate proves to be a
novel multi-functional nanoparticles that combine the advantages of active cancer-targeting through Fe(III) complex mediated intracellular
drug delivery and compatibility with uorescence imaging [37]. Hypocrellin A (HA), a hydrophobic photosensitive anti-cancer drug was delivered to cancer cells in vitro using silica nano-carrier (SNDS) prepared
using microemulsion method. Comparative studies have demonstrated
that the in vitro efcacy of encapsulated HA-SNDS is obvious superior
to free HA [38,39]. Biodegradable amphiphilic poly(ether-anhydride)
gel nanoparticles (GNPs) with a hydrophobic crosslinked core and a hydrophilic PEG shell have been found to be potentially useful to control
the release of hydrophobic drugs. These GNPs were prepared from amphiphilic photo-crosslinkable ether-anhydride macromers via microemulsion photo-polymerization [40]. Sodium uoride catalyzed
hydrolysis of tetraethyl orthosilicate in a water-in-oil microemulsion
was used as a one-pot synthesis of doxorubicin-doped silica nanoparticles
(Dox/SiNPs). It was suggested that Dox/SiNPs modied with the aptamer
sgc8c (sgc8c-Dox/SiNPs) possibly will be a useful new tumor therapy system [41]. Hyaluronic acid hydrogel particles were synthesized in a single
step employing water-in-oil microemulsion system. The particles were
chemically modied to induce desired functional groups on the particle
surface and utilized for potential drug delivery vehicles. Trimethoprim, a
bacteriostatic antibiotic drug, was used as a model drug for the release studies in phosphate buffer solution [42]. Idebenone solid
lipid nanoparticles generated in oil-in-water microemulsions by
the phase-inversion temperature method are regarded as interesting drug delivery. Idebenone release was dependent both on the
type of primary surfactant used and the amount of loaded drug.
The tested solid lipid nanoparticles could be regarded as interesting carriers to overcome the blood brain barrier and increase the efcacy of the
loaded drug [43]. Resveratrol, an anti-cancer, anti-inammatory and
blood sugar-lowering drug, was contained in solid lipid nanoparticles
prepared in microemulsions by hot solvent diffusion method [44].
Solid lipid nanoparticles containing the anti-inammatory drug, aceclofenac, were produced using the Gasco microemulsion method with
three different lipids, namely glyceryl behenate, glyceryl palmitostearate
and cetyl alcohol. It was found that as the drug lipid molar concentration
was raised, particles with a smaller size were obtained irrespective of the
nature of the lipid. The study recommends glyceryl behenate as a suitable candidate for the production of solid lipid nanoparticles [45]. Glyceryl
monostearate solid lipid nanoparticles were generated in a biocompatible
microemulsion as a template. Tretinoin, a lipophilic anti-acne agent was
successfully incorporated into the generated solid lipid nanoparticles as
a model drug [46]. Extracts of Kaempferia parviora were formulated in
solid lipid nanoparticles using oil-in-water microemulsions in order to
improve their transdermal permeability [47]. Solid lipid nanoparticles of
two anthracyclines, idarubicin and doxorubicin were developed from
warm microemulsion precursors comprising emulsifying wax as the oil
phase, and polyoxyl 20-stearyl ether (Brij 78) and D-alpha-tocopheryl
polyethylene glycol succinate (Vitamin E TPGS) as the surfactants. The
present study suggests that the developed solid lipid nanoparticles may
offer potential to deliver anticancer drugs [48]. Solid lipid nanoparticles
have been prepared from oil-in-water microemulsion, using various
monoglycerides as solid matrix, polyethylene glycol sorbitan monooleate
as emulsier, and chloramphenicol as target drug. Effects of types and
concentration of lipids, and surface modiers on drug release behavior
were studied [49]. Ibuprofen loaded magnetic solid lipid nanoparticles
(Ib-MSLNs) were successfully fabricated using a warm oil-in-water
microemulsion [50]. Oil-in-water microemulsions were used to develop

magnetic magnetite (Fe3O4) nanoparticles with zero-valent Fe cores

and magnetite shells. The superior magnetic properties of zero-valent Fe
give these particles the potential for improved specic absorption rate
over pure magnetite particles. This magnetic nanoparticle hyperthermia is believed to opening new doors in cancer therapy [51].
Thermo, pH and magnetic eld responsive coreshell particles of
poly(acrylonitrile-co-N-isopropylacrylamide), a potentially guided drug delivery vehicles, were synthesized by microemulsion polymerization [52]. The chitosan-coated magnetic nanoparticles were
prepared as carriers of 5-uorouracil through a reverse microemulsion
method [53]. Carboxymethyl cellulose (CMC) particles synthesized in
microemulsions and demonstrated as the delivery system of acyclovir
as the model drug. The synthesized CMC particles were made magnetically responsive by encasing independently prepared magnetic ferrite
particles (Fe3O4) in CMC polymeric particles during the synthesis as
magnetic-CMC. It was determined that these particles obtained from
the natural CMC polymers have a potential range of application as drug
delivery systems [54]. Thermosensitive and magnetic nanoparticles
were synthesized by reverse microemulsion and radical polymerization.
Combined thermosensitive and magnetic properties, nanoparticles could
be utilized in controlled drugtargeting delivery [55]. Microemulsions
were also used to synthesize quantum dot-ligand systems that can be effectively used as imaging/contrast agents in live-cell confocal microscopy. The microemulsion technique proved to be highly reproducible,
cheap and controllable, for synthesizing novel transducers for biosensing
[56].
4. Microemulsions as delivery systems
Microemulsions were formulated to be used themselves as carriers
of drugs. Different routes of delivery that include transdermal, dermal,
topical, oral, nasal, ocular, parenteral, and others continued to be investigated in the past ve years.
4.1. Transdermal
Transdermal drug delivery presents both unique opportunities
and obstacles due to skin structure, physiology, and barrier properties. The skin, the biggest organ of the body, may be viewed either
as a natural protective barrier against penetration of toxic exogenous
compounds, excessive loss of water and other essential compounds,
or as a promising portal of entry for drugs for local and/or systemic
action. Particular accumulation of drugs in certain skin layers or in the
blood circulation is the endeavor of (trans-)dermal targeting. The use
of microemulsions has been widely implemented as a strategy to improve the percutaneous transport into and across the skin barrier [1,2].
The determination of the major pathway of penetration and the mechanisms by which these formulations work remain crucial.
Microemulsions based on the commercial surfactants tween 80
and span 80 were formulated and used to solubilize and deliver capsaicin
transdermaly. Capsaicin has a variety of pharmacological actions on the
cardiovascular, respiratory and nervous systems [57]. Microemulsions
containing 10% (w/w) naproxen were investigated as effective alternative
transdermal drug delivery systems. The permeation rates of naproxen
from microemulsions were found to be higher than those from the commercially available gel formulations [58]. Transdermal delivery of hydrophilic drugs (for example, caffeine) was studied in oil-in-water,
water-in-oil, and bicontinuous microemulsions. It was found that caffeine skin absorption is microstructure dependent. The oil-in-water
microstructure allows faster transport of hydrophilic drugs [59].
Waterin-oil microemulsions composed of brine/aerosol-OT/tween 85/
isopropylmyristate were loaded with uorouracil for transdermal delivery. The penetration ux of uorouracil across excised mice skin was determined in vitro using Franz diffusion cells. It was found that the
cumulative amount of uorouracil permeated in 12 h was 20 folds and
10 folds more than 0.7% uorouracil aqueous solution and 2.5% (w/w)

M. Fanun / Current Opinion in Colloid & Interface Science 17 (2012) 306313

uorouracil cream, respectively [60]. The intradermal delivery of a hydrophilic polyphenol chlorogenic acid solubilized in microemulsions
was examined by in vitro study using excised guinea pig dorsal skin
and Yucatan micropig skin. It was found that the enhancement effect of
oil-in-water microemulsion was greater than that of a water-in-oil
microemulsion possibly due to the greater increase in solubility. These
ndings signify the potential use of hydrophilic chlorogenic acid with
oil-in-water microemulsion as a vehicle to protect the skin against
UV-induced oxidative damage [61]. The use of curcumin for treating various skin diseases such as scleroderma, psoriasis, and skin cancer was
extensively reported [62,63]. Microemulsion systems composed of eucalyptol, polysorbate 80, ethanol, and water were developed as transdermal delivery vehicles for curcumin. The curcumin permeation rate
of the developed microemulsion was 15.7-fold higher than that of the
control (eucalyptol only). Developed microemulsions are a promising
tool for the percutaneous delivery of curcumin [62]. Microemulsion
systems composed of three terpenes (limonene, 1,8-cineole, and
-terpineol), polysorbate 80, cosurfactants, and water were also investigated as transdermal delivery vehicles for curcumin. It was
shown that limonene microemulsion system is a promising tool for
the percutaneous delivery of curcumin [63]. The transdermal administration of nicardipine microemulsions was developed. The permeation
rate and extent of nicardipine microemulsion transport across rat skin
were affected by the ingredients for microemulsion [64]. Microemulsions
were considered as potentially useful vehicles for the transdermal delivery of testosterone. The characterization of the drug loaded microemulsions demonstrated that the drug was mainly located in the oily
domains of the microemulsions. Testosterone was delivered across the
skin from the microemulsions studied, with the highest ux achieved
(4.60.6 g cm2 h1) [65]. The microstructures of meloxicam loaded
microemulsion had accounted for the solubilization potential and transdermal permeation. It was found that water-in-oil microemulsions had
the best solubilization potential, followed by the bicontinuous and the
oil-in-water system, and that oil-in-water microemulsions had the best
permeation rate, followed by the bicontinuous and the water-in-oil
type [66]. Novel oil-in-water microemulsions of ketoprofen for improving transdermal absorption were formulated. The diffusion rate of
ketoprofen from formulation was fast and rapid than the marketed sample [67]. Microemulsions based on a vegetable protein surfactant
and 1,2-alkanediols as co-surfactant and loaded with model drug
dihydroavenanthramide D were developed for transdermal delivery. The formulation demonstrated adequate penetration into viable skin layers and predominantly high permeation rates [68]. A
water-in-oil microemulsion containing dihydroquercetin (DHQ)
(2%) was prepared. Physicochemical parameters and the in vitro
release of DHQ were studied. The proposed microemulsion ensures
uniform prolonged release of the active substance [69]. Microemulsions containing medium-chain glycerides as penetration enhancers were formulated to enhance the transdermal delivery of
lipophilic (progesterone) and hydrophilic (adenosine) model drugs
[70]. An aerosol-OT included microemulsion loaded with uorouracil
was formulated by using appropriate proportion of oil, co-surfactant
and water for increasing the drug transdermal delivery ability [71].
Linker-based lecithin microemulsions were reported as effective transdermal delivery vehicles for lidocaine [72]. Microemulsions were found
to be a promising vehicle for temozolomide acid hexyl ester transdermal delivery [73]. Microemulsion-based hydrogel (MBH) that was considered as promising vehicle transdermal delivery of sinomenium was
developed and evaluated. The transdermal capability of different microemulsion formulations were evaluated in vitro using Franz diffusion
cells tted with rat skins and sinomenium was analyzed by HPLC. Pharmacokinetic study in vivo was performed using rabbits, and the area
under curve of plasma concentration-time (AUC0) of MBH was 1.27
times greater than that of the hydrogel [74]. A microemulsion-based hydrogel formulation was constructed for the transdermal delivery of dexamethasone. Almond oil, olive oil, linseed oil, and nutmeg oil were

309

screened as the oil phase. The capability of various microemulsion formulations to deliver dexamethasone through the rat skin was assessed
in vitro using Keshary Chien diffusion cells. It was demonstrated that
microemulsion-based transdermal systems are a promising formulation
for dermal delivery of dexamethasone [75]. A hydrogel-thickened microemulsion (HTM) was explored for delivering an extremely low concentration of triptolide as a model drug. The powerful permeation
enhancing capability of HTM with an appropriate viscosity makes it
a promising alternative transporter for the transdermal administration of drug molecule at a very low concentration [76]. Microemulsions
formulated using components that are normally present in the skin
were considered as a promising strategy for enhancing skin protection
from oxidative stress by delivering antioxidants such as vitamins C
and E into the skin simultaneously [77]. The composition of microemulsions affected the permeability of buspirone hydrochloride through
rat skin. This study demonstrated that microemulsions could be a
promising drug carrier for transdermal delivery systems [78]. Several anti-inammatory drugs applied in the treatment of skin diseases
have been incorporated into skin delivery cyclodextrin-based microemulsions [79]. The feasibility of using microemulsion for transdermal
delivery of tolterodine tartrate was investigated. Drug pharmacokinetics was studied after transdermal application to human volunteers
and a sustained activity due to the controlled release of drug was observed [80]. A skin permeation study for testing the penetration effect
of various curcumin loadings in oil-in-water biocompatible microemulsion with different particle diameters was performed [81]. In vitro
skin permeation of microemulsion drug delivery system containing uconazole (FLZ) was investigated. The efciency of microemulsion formulation in the topical delivery of FLZ was dependent upon its composition.
Candida albicans was used as a model fungus to assess the antifungal action of the best prescription attained, which demonstrated the widest region of inhibition as compared to FLZ cnce [82]. The permeating ability of
penciclovir was signicantly increased from the microemulsion formulation compared with commercial cream [83].
4.2. Topical
Low-surfactant microemulsion gels were formulated and characterized to enhance topical delivery of poorly soluble drugs. It was found
that the choice of viscosity imparting agent (Xanthan gum or Carbopol
934) played an important role in governing drug release from microemulsion gels [84]. Ketoconazole loaded microemulsion for percutaneous absorption showed a good stability for a period of three months. It
was found that the percutaneous absorption of ketoconazole depends
on microemulsion composition. Histopathological investigation of rat
skin revealed the safety of microemulsion formulations for topical use
[85]. A novel dithranol-containing phospholipid microemulsion system
was developed and characterized for enhanced skin permeation and retention. The results propose that the developed microemulsion systems
have a promising potential to improve topical delivery of dithranol [86].
Oxymatrine (OMT), a water-soluble drug, has a very low oral bioavailability. Formulated oxymatrinephospholipid complex (OMTPLC) can
improve the lipid solubility and effectiveness of OMT. A combination of
a microemulsion and an OMTPLC represents an effective vehicle for
topical delivery of OMT [87]. Due to its poor oral bioavailability, a topical
drug delivery system of griseofulvin (GF) is needed. A griseofulvin loaded into solid lipid nanoparticles was prepared using a simple microemulsion technique. The GF release was to be a prolong release of
63.53% within 12 h [88]. Microemulsions incorporated into l% carbopol
974P gel base containing terbinane hydrochloride were formulated
and evaluated for topical delivery. The release controlling ability of
microemulsion containing gel formulations was signicantly improved
in comparison to commercial cream [89]. A topical preparation containing aceclofenac was developed using an oil-in-water microemulsion
system. In vitro permeability of aceclofenac from the microemulsions
was evaluated. The results indicate that the microemulsion system

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M. Fanun / Current Opinion in Colloid & Interface Science 17 (2012) 306313

studied is a promising tool for percutaneous delivery of aceclofenac [90].

Lecithinsed microemulsions were prepared and evaluated as topical delivery vehicles of tretinoin [91]. The addition of colloidal silica in microemulsions simultaneously loaded with vitamins C and E enhanced skin
bioavailability of vitamins by its dual inuence on delivery characteristics of microemulsions as well as on skin properties [92]. A
three-compartment (donor, skin, and receiver) mass balance model was
introduced to describe the effect of surfactant content on lecithin-linker
microemulsion-mediated topical transport. The model was used to t
the permeation prole of lidocaine formulated in different microemulsion
types. It was demonstrated that surfactant concentration has a fairly small
effect on the mass transfer coefcients, suggesting that permeation enhancement via disruption of the structure of the skin is not a relevant
mechanism in these microemulsions [93]. Microemulsions containing
5-aminolevulinic acid (5-ALA) were formulated and characterized for
topical photodynamic therapy. The microemulsion developed carried
5-ALA to the deeper skin layers [94]. Microemulsion formulation was
designed for hesperetin topical dosage form. In vivo study revealed that
the hesperetin-loaded microemulsion showed considerable topical whitening effect and reduced skin irritation when compared
with the non-treatment group [95]. Microemulsions containing
mono-diglycerides were found to be an efcient and safe system
to increase lycopene delivery to the skin and the antioxidant activity in the tissue [96]. The in vitro release of valdecoxib incorporated in microemulsion based emulgel formulations was increased as
the proportion of the surfactant (tween-80) increased. Maximum
amount of valdecoxib gets partitioned in stratum corneum with
the highest amount of tween-80 [97]. Dexamethasone microemulsion
systems were investigated as potential drug delivery vehicles. The permeation data demonstrated that microemulsion formulations enhanced
dexamethasone ux 200400 fold over the control, but permeability coefcients were reduced by 4 times. The superior transdermal ux of
dexamethasone was due to 1000-fold improvement in the solubilization
of dexamethasone by microemulsions using lecithin [98]. Water-in-oil
microemulsion as a carrier signicantly increased the intradermal delivery of quercetin where it exerts antioxidative effects [99]. Microemulsions were formulated using 1-decanol, oleic acid or oleyl alcohol
as oils to verify the effect of the oils on pig-skin permeation and accumulation of acyclovir (ACV). The presence of oleyl alcohol or oleic acid increased the ux but not the drug skin accumulation compared to a
control suspension. A two-fold increase in ACV accumulation was found
using the microemulsions containing 1-decanol, maintaining intact the
structure of the stratum contemn [100,101]. Microemulsions incorporating both lipophilic (vitamin E) and hydrophilic (vitamin C) antioxidants
were formulated for skin protection against free radical damage. The absorption of vitamins C and E in reconstructed human epidermis (RHE)
layers was in general enhanced by microemulsions compared to solutions. By varying the composition of microemulsions, RHE absorption of
the two vitamins can be considerably adjusted [102]. Microemulsion systems were examined as possible carriers for enhanced skin bioavailability
of cyclosporin A (CysA). In rat dermal applied with the bicontinuous
microemulsion containing CysA, the deposition of the drug into the skin
and subcutaneous fat was respectively almost 30 and 15-fold higher
than the concentrations compared with oral administration. Systemic distribution in the blood, liver and kidney was much lower following topical
administration than that following oral administration Topical delivery of
CysA is of immense concern for the cure of autoimmune skin disorders.
With elevated local concentrations and least distribution to other organs
via the distribution, topical microemulsion vehicle loaded with CysA
might deliver maximal therapeutic effect to the local tissue while
avoiding side effects seen with systemic therapy [103]. Topical microemulsion of capsaicin without surfactant was developed. In the system
composed of water, benzyl alcohol and propylene glycol, the permeation rate increased with the enhancement of benzyl alcohol and
water. But water content had little effect on the permeation rate in
the microemulsions with ethanol as cosurfactant [104].

4.3. Oral
More than forty percent of new chemical entities exhibit poor
aqueous solubility, resulting in unsatisfactory oral drug delivery.
Microemulsion can signicantly improve the oral bioavailability of
hydrophobic drugs [1,2]. Double microemulsions (O/W/O) were
prepared to enhance the bioavailability of erythromycin base
when administered orally in rainbow trout. The results proved that
the feeds containing microemulsied erythromycin provided largely
superior oral bioavailability and the advantage of obtaining the
same efcacy against bacterial infections with a much lower dose
of drug compared to oral administration of feed with erythromycin
powder [105]. Therapeutic peptides are highly effective and specic
in their functions, but difculties in their oral intake require parallel
development of practical delivery systems. In order to improve the
oral bioavailability of salmon calcitonin it was encapsulated in
water-in-oil microemulsions prepared from medium chain triglyceride, tween 80 and span 80 or soybean phosphatidylcholine,
propylene glycol and phosphate saline with the addition of the polymers such as hydroxypropylmethylcellulose and carbomer into the
aqueous phase. The optimized microemulsions were shown to
cause up to a 4-fold enhancement of relative pharmacological activity of salmon calcitonin with regard to the control solution of the
drug [106]. Oral bioavailability of sirolimus was improved using
self-microemulsifying drug delivery systems. The effect of the
amount of oil and surfactant on the transport of sirolimus was investigated and it was found that more oil content presented higher
lymphatic transport, while more surfactant content increased the
intestinal absorption of the drug [107]. Curcumin was solubilized
in ne oil-in-water microemulsions that were rapidly formulated
via self-microemulsifying drug delivery systems in liquid and pellet
forms. These systems result in improved solubility, dissolution, and
in vivo oral absorption of the poorly water-soluble compound.
These studies revealed that the new self-microemulsifying systems
in liquid and pellet forms are promising strategies for the formulation of poorly soluble lipophilic compounds with low oral bioavailability [108]. Insulin loaded microemulsions were developed
adopting a low shear reverse micellar approach as a potential carrier for oral delivery [109]. A microemulsion system of docetaxel
was formulated and assessed for its solubilization capacity and
oral bioavailability enhancement [110]. Cremophor-free oral microemulsions of paclitaxel (PAC) were developed to enhance its
permeability and oral absorption. The developed microemulsion
systems increased both the permeability and area under the curve
of PAC as compared to cremophor [111]. A novel water-in-oil (W/
O) microemulsion was formulated for the oral delivery of hydrophilic protein drug using the earthworm brinolytic enzyme
(EFE-d, Mw 24177) as a model protein drug. This study shows
that the W/O microemulsion may represent an effective oral delivery system for hydrophilic bioactive macromolecules [112]. The
oral bioavailability of earthworm brinolytic enzyme (EFE-d)
used for the management of cardiovascular diseases from microemulsions was 208-fold higher than that of control solution and
the absolute bioavailability was 17.55%. No tissue damage of the
intestinal mucosa found after oral multiple-dose administration
of the EFE-d microemulsion to rats [113]. Self-microemulsifying
drug delivery system was formulated for improving oral absorption of poorly water-soluble drug, silymarin [114], and daidzein
[115]. The dissolution rate of daidzein from the formulated systems was considerably higher than the conventional tablet. Relative bioavailability of the drug loaded system was increased to
about 2.5-fold compared with that of the control group [115]. Another
self-microemulsifying drug delivery system was suggested as a promising drug delivery system to increase the oral bioavailability and antitumor effects of 9-Nitrocamptothecin and represents a novel therapy
for cancer patients [116].

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4.4. Nasal
Topical microemulsions can be a useful option to reduce nasal mucosal exposure to allergen in perennial allergic rhinitis [117]. The bioavailability of insulin lispro via the nasal route using a water-in-oil
microemulsion was found to reach 21.5% relative to subcutaneous administration, whereas the use of an inverse microemulsion as well as
a plain solution yielded less than 1% bioavailability in rabbits. It has
been concluded that the speeding up in the intramucosal transport
process is the result of encapsulating insulin within the nano-droplet
clusters of a water-in-oil microemulsion, while the microemulsion components seem to have no direct role. [118]. Intranasal oilin-water microemulsion of zonisamide with labrasol as surfactant and transcutol as
cosurfactant was developed for direct brain drug delivery. In vitro drug
diffusion studies of developed microemulsions based formulation were
carried out through sheep nasal mucosa using Franz diffusion cell. The effects of mucoadhesive agent and different penetration enhancers were
also evaluated in the diffusion studies. In vitro drug diffusion study revealed that the microemulsions have signicantly increased the drug
diffusion across the nasal mucosa [119]. Fexofenadine loaded microemulsion system was developed for intranasal delivery. These systems were suggested as an effective intranasal dosage form for
the rapid-onset delivery of fexofenadine [120]. Sertraline hydrochloride (STH) was solubilized in microemulsions by titration method
and assessed. In vitro studies for nasal absorption were carried out on
goat nasal mucosa. The results show that intranasal microemulsion of
STH could be useful for the treatment of depression [121]. A microemulsion system for intranasal delivery of lorazepam was developed.
In vivo absorption studies showed that intranasal absorption of lorazepam from microemulsions was enhanced as compared to the intramuscular injection [122].
4.5. Ocular
The most common approach for administering ophthalmic drugs
is the ocular drug delivery. Microemulsions are particularly attractive
for delivering hydrophobic drugs to the cornea because of the possibility of loading the drugs in the oil particle [123]. Prednisolone solutions were prepared in self-microemulsifying drug delivery systems.
The physical properties of the formulations were observed and the
chemical potency of the drug was determined using a stability indicating HPLC method. It was found that water-in-oil microemulsions
can protect prednisolone from degradation by gamma ionizing radiation
[124]. Nanostructured poly(2-hydroxyethyl methacrylate) (p-HEMA)
hydrogels containing microemulsions or micelles of Brij 97 were developed for extended delivery of Cyclosporine A (CyA), an immunosuppressant drug that is used for treating a variety of ocular diseases and
disorders. Results show that the surfactant and microemulsion-laden
gels can deliver CyA at therapeutic dosages for a period of about
20 days [125].
4.6. Parenteral
Microemulsions have evolved as a novel vehicle for parenteral delivery of the hydrophobic drugs [126]. Phospholipid-based microemulsions were formulated and examined for parenteral delivery of
anticancer drug, etoposide. To evaluate the safety of the formulations
for parenteral delivery, it was subjected to compatibility studies with
various intravenous infusions and in vitro erythrocyte toxicity study.
The developed formulation was found to be robust and safe [127].
Lorazepam (LZM) microemulsions were developed as a substitute to
the conventional cosolvent based formulation. The LZM microemulsions
were assessed for compatibility with parenteral uids, globule size, in
vitro hemolysis and stability of LZM. The LZM microemulsions containing
amino acids exhibited good physical and chemical stability when subjected to refrigeration for 6 months [128]. Blank and -elemene-loaded

311

microemulsions were prepared and characterized using transmission

electron microscopy, conductivity and viscosity. The loading capacity
test, dilutability test, and the inuence of antioxidants were conducted
for further optimization of -elemene-loaded microemulsion. The in
vitro release study showed that -elemene was progressively released
until 12 h, which most tted the rst order [129]. Microemulsion formulations were formulated as alternative carrier for intravenous delivery of
docetaxel. The solubility of the drug docetaxel was enhanced and the
loaded microemulsions were methodically assessed in vitro and in vivo
[130].
4.7. Others
Microemulsions were compared with other adjuvants evaluated and
were found to be the best candidate for rabies immunization as they
presented good potency against the virus and did not appear to cause
any local reaction [131]. Microemulsions were discussed with their
merits and demerits as non vesicular form of delivery systems of articial
blood substitutes [132]. Bee propolis ethanolic extract was incorporated
in microemulsions to be applied as a pressurized aerosol [133].
5. Conclusions
The following important points could be summarized from the
reviewed studies:
a. Microemulsions enhance the solubilization capacity and dissolution efciency of poorly soluble drugs.
b. Drug solubilization capacity and dissolution efciency are reliant
on the microstructure of the microemulsions.
c. Solubilized drugs may inuence the boundaries of structural regions and the transition point between different microemulsion
microstructures.
d. Drug extent and route of delivery could be inuenced by the microstructure of the microemulsions.
e. Drug delivery systems generated in microemulsions improved
drug release and compatibility.
f. The extent and rate of drug delivery are dependent on the generated system preparation method in microemulsions.
g. The generated system could inuence the selection of a delivery
route.
h. In all routes of delivery, the microemulsion type and microstructure affects the extent and rate of drug delivery.
References
[1] Fanun M. Microemulsions properties and applications. New York: Taylor and
Francis; 2009.
[2] Fanun M. Colloids in drug delivery. New York: Taylor and Francis; 2010.
[3] Fanun M, Papadimitriou V, Xenakis A. Characterization of cephalexin loaded
nonionic microemulsions. J Colloid Interface Sci 2011;361:11521.
[4] Dong X, Ke X, Liao Z. The microstructure characterization of meloxicam microemulsion and its inuence on the solubilization capacity. Drug Dev Ind Pharm
2011;37:894900.
[5] Furlanetto S, Cirri M, Piepel G, Mennini N, Mura P. Mixture experiment methods
in the development and optimization of microemulsion formulations. J Pharm
Biomed Anal 2011;55:6107.
[6] Kumar A, Agarwal SP, Ahuja A, Ali J, Choudhry R, Baboota S. Preparation, characterization, and in vitro antimicrobial assessment of nanocarrier based formulation of nadioxacin for acne treatment. Pharmazie 2011;66:1114.
[7] Fanun M, Glatter O. SAXS study on azithromycin loaded nonionic microemulsions.
Tenside Surfactants Deterg 2011;48:349.
[8] Chen Y, Lu H, Song S, Jia X. Preparation of Ganoderma lucidum polysaccharides
and triterpenes microemulsion and its anticancer effect in mice with transplant
Heps tumors. Zhongguo Zhongyao Zazhi 2010;35:267983.
[9] Fanun M. Solubilization of celecoxib in microemulsions based on mixed nonionic
surfactants and peppermint oil. J Dispers Sci Technol 2010;31:11409.
[10] Kamila MM, Mondal N, Gupta BK, Ghosh LK. Preparation, characterization and
in-vitro evaluation of sunower oil-tween 80-glycerol-based microemulsion
formulation of a BCS class-II drug. Lat Am J Pharm 2009;28:6227.
[11] Fanun M. Oil type effect on diclofenac solubilization in mixed nonionic surfactants microemulsions. Colloids Surf A Physicochem Eng Asp 2009;343:7582.

312

M. Fanun / Current Opinion in Colloid & Interface Science 17 (2012) 306313

[12] Fanun M. Diclofenac solubilization in microemulsions based on mixed nonionic

surfactants and R (+)-limonene. J Dispers Sci Technol 2010;31:93644.
[13] Chen H, Xiao L, Du D, Mou D, Xu H, Yang X. A facile construction strategy of stable lipid nanoparticles for drug delivery using a hydrogel-thickened microemulsion system. Nanotechnology 2010;21:015101.
[14] Kogan A, Aserin A, Garti N. Improved solubilization of carbamazepine and structural
transitions in nonionic microemulsions upon aqueous phase dilution. J Colloid Interface Sci 2007;315:63747.
[15] Nisha GS, Vaishali P, Geeta R, Prabhakar P, Harish NM, Marina K, et al. Formulation and evaluation of self microemulsifying drug delivery system of carbamazepine. Int J Res Pharm Sci 2011;2:1629.
[16] Formariz TP, Chiavacci LA, Sarmento VHV, Santilli CV, Tabosa do Egito ES,
Oliveira AG. Relationship between structural features and in vitro release of
doxorubicin from biocompatible anionic microemulsion. Colloids Surf B Biointerfaces 2007;60:2835.
[17] Sakai K, Yoshimori T, Obata K, Maeda H. Design of self-microemulsifying drug
delivery systems using a high-throughput formulation screening system. Drug
Dev Ind Pharm 2010;36:124552.
[18] Dora CL, Silva LFC, Tagliari MP, Silva MAS, Lemos-Senna E. Formulation study of
quercetin-loaded lipid-based nanocarriers obtained by hot solvent diffusion
method. Lat Am J Pharm 2011;30:289.
[19] Mehta SK, Kaur G, Bhasin KK. Analysis of tween based microemulsion in the
presence of TB drug rifampicin. Colloids Surf B Biointerfaces 2007;60:95104.
[20] Nazar MF, Khan AM, Shah SS. Microemulsion system with improved loading of
piroxicam: a study of microstructure. AAPS PharmSciTech 2009;10:128694.
[21] Lee MH, Yu MW, Kao L, Lin CC. Enhancement of the encapsulation and transmembrane permeation of isoavone-containing red clover extracts in
phospholipid-based microemulsions using different extraction processes. J Agric
Food Chem 2009;57:948995.
[22] Dixit RP, Nagarsenker MS. Optimized microemulsions and solid microemulsion
systems of simvastatin: characterization and in vivo evaluation. J Pharm Sci
2010;99:4892902.
[23] Lin YH, Chen YS, Wu TC, Chen LJ. Enhancement of dissolution rate of mitotane and
warfarin prepared by using microemulsion systems. Colloids Surf B Biointerfaces
2011;85:36672.
[24] Sun Y, Jiang Y, An K. Preparation and the inuencing factors of cetirizine hydrochloride microemulsion. Artif Cells Blood Substit Biotechnol 2011;39:1746.
[25] ner M, Yetiz E, Ay E, Uysal U. Ibuprofen release from porous hydroxyapatite
tablets. Ceram Int 2011;37:211725.
[26] Wang Z, Cai Z, Guo Q. Tunable amphiphilic poly(ether-anhydride) gel nanoparticles
for the delivery of hydrophobic drugs. Macromol Symp 2010;297:16778.
[27] Lu CH, Zhang QW, Jia Y. Preparation and characterisation of triangular
pyramid-shaped puerarin and aspirin microparticles with nanostructures. J
Exp Nanosci 2011;6:16.
[28] Paillard A, Hindr F, Vignes-Colombeix C, Benoit JP, Garcion E. The importance of
endo-lysosomal escape with lipid nanocapsules for drug subcellular bioavailability. Biomaterials 2010;31:754254.
[29] Ekici S, Ilgin P, Butun S, Sahiner N. Hyaluronic acid hydrogel particles with tunable charges as potential drug delivery devices. Carbohydr Polym 2011;84:
130613.
[30] Moniruzzaman M, Tamura M, Tahara Y, Kamiya N, Goto M. Ionic liquid-in-oil
microemulsion as a potential carrier of sparingly soluble drug: characterization
and cytotoxicity evaluation. Int J Pharm 2010;400:24350.
[31] Margulis-Goshen K, Kesselman E, Danino D, Magdassi S. Formation of celecoxib
nanoparticles from volatile microemulsions. Int J Pharm 2010;393:2307.
[32] Margulis-Goshen K, Weitman M, Major DT, Magdassi S. Inhibition of crystallization and growth of celecoxib nanoparticles formed from volatile microemulsions. J Pharm Sci 2011;100:4390400.
[33] Chen H, Xiao L, Du D, Mou D, Xu H, Yang X. A facile construction strategy of stable lipid nanoparticles for drug delivery using a hydrogel-thickened microemulsion system. Nanotechnology 2010;21 [art. no. 015101].
[34] Margulis-Goshen K, Magdassi S. Formation of simvastatin nanoparticles from
microemulsion. Nanomedicine 2009;5:27481.
[35] Graf A, Rades T, Hook SM. Oral insulin delivery using nanoparticles based on
microemulsions with different structure-types: optimisation and in vivo evaluation. Eur J Pharm Sci 2009;37:5361.
[36] Krauel K, Girvan L, Hook S, Rades T. Characterisation of colloidal drug delivery
systems from the naked eye to cryo-FESEM. Micron 2007;38:796803.
[37] Tao GP, Chen QY, Yang X, Zhao KD, Gao J. Targeting cancer cells through iron(III)
complexes of di(picolyl)amine modied silica coreshell nanospheres. Colloids
Surf B Biointerfaces 2011;86:10610.
[38] Zhou L, Wang W, Wei SH, Feng YY, Zhou JH, Liu JH, et al. Encapsulation of hydrophobic
anticancer drug in nano-scale porous ceramic materials for photodynamic therapy.
J Porous Mater 2011;18:51722.
[39] Zhou L, Ning YW, Wei SH, Feng YY, Zhou JH, Yu BY, et al. A nanoencapsulated
hypocrellin A prepared by an improved microemulsion method for photodynamic treatment. J Mater Sci Mater Med 2010;21:2095101.
[40] Wang Z, Zhou B, Liu D, Fan XP. Thermosensitive Poly(N-isopropylacrylamide)-g
-Polyamidoamine Dendrimer Derivatives: Preparation and the Drug Release
Behaviors. Macromolecular Symposia 2010;297:15866.
[41] He X, Hai L, Su J, Wang K, Wu X. One-pot synthesis of sustained-released doxorubicin silica nanoparticles for aptamer targeted delivery to tumor cells. Nanoscale 2011;3:293642.
[42] Ilgin P, Avci G, Silan C, Ekici S, Aktas N, Ayyala RS, et al. Colloidal drug carries
from (sub)micron hyaluronic acid hydrogel particles with tunable properties
for biomedical applications. Carbohydr Polym 2010;82:9971003.

[43] Montenegro L, Campisi A, Sarpietro MG, Carbone C, Acquaviva R, Raciti G, et al. In

vitro evaluation of idebenone-loaded solid lipid nanoparticles for drug delivery
to the brain. Drug Dev Ind Pharm 2011;37:73746.
[44] Nemen D, Lemos-Senna E. Preparation and characterization of resveratrol-loaded
lipid-based nanocarriers for cutaneous administration. Quimica Nova 2011;34:
40813.
[45] Chawla V, Saraf SA. Glyceryl behenate and its suitability for production of aceclofenac solid lipid nanoparticles. J Am Oil Chem Soc 2011;88:11926.
[46] Shah KA, Joshi MD, Patravale VB. Biocompatible microemulsions for fabrication
of glyceryl monostearate solid lipid nanoparticles (SLN) of tretinoin. J Biomed
Nanotechnol 2009;5:396400.
[47] Sutthanut K, Lu X, Jay M, Sripanidkulchai B. Solid lipid nanoparticles for topical administration of Kaempferia parviora extracts. J Biomed Nanotechnol 2009;5:22432.
[48] Ma P, Dong X, Swadley CL, Gupte A, Leggas M, Ledebur HC, et al. Development of
idarubicin and doxorubicin solid lipid nanoparticles to overcome Pgp-mediated
multiple drug resistance in leukemia. J Biomed Nanotechnol 2009;5:15161.
[49] Li XW, Lin XH, Zheng LQ, Yu L, Mao HZ. Preparation, characterization, and in
vitro release of chloramphenicol loaded solid lipid nanoparticles. J Dispers Sci
Technol 2008;29:121421.
[50] Pang XJ, Zhou J, Chen JJ, Yu MH, Cui FD, Zhou WL. Synthesis of ibuprofen loaded
magnetic solid lipid nanoparticles. IEEE Trans Magn 2007;43:24157.
[51] Cassim SM, Giustini AJ, Baker I, Hoopes PJ. Development of novel magnetic
nanoparticles for hyperthermia cancer therapy. Prog Biomed Opt Imaging Proc
SPIE 2011;7901 [art. no. 790115].
[52] Sahingr N, Ilsin P. Soft coreshell polymeric nanoparticles with magnetic property for potential guided drug delivery. Curr Nanosci 2010;6:48391.
[53] Zhu L, Ma J, Jia N, Zhao Y, Shen H. Chitosan-coated magnetic nanoparticles as carriers of 5-uorouracil: preparation, characterization and cytotoxicity studies.
Colloids Surf B Biointerfaces 2009;68:16.
[54] Butun S, Ince FG, Erdugan H, Sahiner N. One-step fabrication of biocompatible
carboxymethyl cellulose polymeric particles for drug delivery systems. Carbohydr Polym 2011;86:63643.
[55] Lien YH, Wu TM. The application of thermosensitive magnetic nanoparticles in
drug delivery. Adv Mater Res 2008;4750(PART 1):52831.
[56] Saran AD, Sadawana MM, Srivastava R, Bellare JR. An optimized quantum
dot-ligand system for biosensing applications: evaluation as a glucose biosensor.
Colloids Surf Physicochem Eng Aspects 2011;384:393400.
[57] Tavano L, Alfano P, Muzzalupo R, De Cindio B. Niosomes vs microemulsions: new carriers for topical delivery of capsaicin. Colloids Surf B Biointerfaces 2011;87:3339.
[58] stnda Okur N, Apaydin S, Karabay Yavao lu NU, Yavao lu A, Karasulu HY.
Evaluation of skin permeation and anti-inammatory and analgesic effects of
new naproxen microemulsion formulations. Int J Pharm 2011;416:13644.
[59] Burke KB, Stapleton AJ, Vaughan B, Zhou X, Kilcoyne ALD, Belcher WJ, et al. Scanning transmission X-ray microscopy of polymer nanoparticles: probing morphology on sub-10 nm length scales. Nanotechnology 2011;22 [art. no. 265710].
[60] XiaoYY Liu F, Chen ZP, Ping QN. Water in oil microemulsions containing NaCl for
transdermal delivery of uorouracil. Yaoxue Xuebao 2011;46:7206.
[61] Kitagawa S, Yoshii K, Morita SY, Teraoka R. Efcient topical delivery of chlorogenic
acid by an oil-in-water microemulsion to protect skin against UV-induced damage.
Chem Pharm Bull 2011;59:7936.
[62] Liu CH, Chang FY. Development and characterization of eucalyptol microemulsions
for topic delivery of curcumin. Chem Pharm Bull 2011;59:1728.
[63] Liu CH, Chang FY, Hung DK. Terpene microemulsions for transdermal curcumin
delivery: effects of terpenes and cosurfactants. Colloids Surf B Biointerfaces
2011;82:6370.
[64] Wu PC, Lin YH, Chang JS, Huang YB, Tsai YH. The effect of component of microemulsion for transdermal delivery of nicardipine hydrochloride. Drug Dev Ind
Pharm 2010;36:1398403.
[65] Hathout RM, Woodman TJ, Mansour S, Mortada ND, Geneidi AS, Guy RH. Microemulsion formulations for the transdermal delivery of testosterone. Eur J Pharm
Sci 2010;40:18896.
[66] Dong XH, Ke X. Effect of structure of meloxicam microemulsion on transdermal
properties. J China Pharm Univ 2010;41:2359.
[67] Dhamankar AK, Manwar JV, Kumbhar DD. The novel formulation design of O/W
microemulsion of ketoprofen for improving transdermal absorption. Int J PharmTech
Res 2009;1:144957.
[68] Heuschkel S, Wohlrab J, Neubert RHH. Dermal and transdermal targeting of
dihydroavenanthramide D using enhancer molecules and novel microemulsions.
Eur J Pharm Biopharm 2009;72:55260.
[69] Karlina MV, Pozharitskaya ON, Shikov AN. Development and in vitro biopharmaceutical evaluation of a dihydroquercetin microemulsion. Pharm Chem J 2009;43:
3524.
[70] Hosmer J, Reed R, Bentley MVLB, Nornoo A, Lopes LB. Microemulsions containing
medium-chain glycerides as transdermal delivery systems for hydrophilic and
hydrophobic drugs. AAPS PharmSciTech 2009;10:58996.
[71] Liu F, Xiao YY, Ping QN, Yang C. Water in oil microemulsions for transdermal delivery of uorouracil. Yaoxue Xuebao 2009;44:5407.
[72] Yuan JS, Acosta EJ. Extended release of lidocaine from linker-based lecithin
microemulsions. Int J Pharm 2009;368:6371.
[73] Suppasansatorn P, Nimmannit U, Conway BR, Du L, Wang Y. Microemulsions as
topical delivery vehicles for the anti-melanoma prodrug, temozolomide hexyl
ester (TMZA-HE). J Pharm Pharmacol 2007;59:78794.
[74] Gui S, Pan E, Liu P, Lu C, Peng D. Development of novel microemulsion-based hydrogel for topical delivery of sinomenium. Lat Am J Pharm 2011;30:9316.
[75] Chandra A, Sharma PK, Irchhiaya R. Microemulsion-based hydrogel formulation
for transdermal delivery of dexamethasone. Asian J Pharm 2009;3:306.

M. Fanun / Current Opinion in Colloid & Interface Science 17 (2012) 306313

[76] Chen H, Mou D, Du D, Chang X, Zhu D, Liu J, et al. Hydrogel-thickened microemulsion for topical administration of drug molecule at an extremely low concentration. Int J Pharm 2007;341:7884.
[77] Gaperlin M, Gosenca M. Main approaches for delivering antioxidant vitamins through the skin to prevent skin ageing. Expert Opin Drug Deliv
2011;8:90519.
[78] Tsai YH, Chang JT, Chang JS, Huang CT, Huang YB, Wu PC. The effect of component of microemulsions on transdermal delivery of buspirone hydrochloride. J
Pharm Sci 2011;100:235865.
[79] Oliveira R, Coelho P. Cyclodextrin-based carriers for topical delivery of
anti-inammatory agents. Anti-Inamm Anti-Allergy Agents Med Chem 2011;10:
2309.
[80] Elshafeey AH, Kamel AO, Fathallah MM. Utility of nanosized microemulsion for
transdermal delivery of tolterodine tartrate: ex-vivo permeation and in-vivo
pharmacokinetic studies. Pharm Res 2009;26:244653.
[81] Lin CC, Lin HY, Chen HC, Yu MW, Lee MH. Stability and characterisation of
phospholipid-based curcumin-encapsulated microemulsions. Food Chem 2009;116:
9238.
[82] Patel MR, Patel RB, Parikh JR, Solanki AB, Patel BG. Effect of formulation components on the in vitro permeation of microemulsion drug delivery system of uconazole. AAPS PharmSciTech 2009;10:91723.
[83] Zhu W, Yu A, Wang W, Dong R, Wu J, Zhai G. Formulation design of microemulsion for dermal delivery of penciclovir. Int J Pharm 2008;360:18490.
[84] Shalviri A, Sharma A, Patel D, Sayani A. Low-surfactant microemulsions for enhanced topical delivery of poorly soluble drugs. J Pharm Sci 2011;14:31524.
[85] Patel MR, Patel RB, Parikh JR, Solanki AB, Patel BG. Investigating effect of microemulsion components: in vitro permeation of ketoconazole. Pharm Dev Technol
2011;16:2508.
[86] Raza K, Negi P, Takyar S, Shukla A, Amarji B, Katare OP. Novel dithranol phospholipid microemulsion for topical application: development, characterization and
percutaneous absorption studies. J Microencapsul 2011;28:1909.
[87] Cao FH, OuYang WQ, Wang YP, Yue PF, Li SP. A combination of a microemulsion and a
phospholipid complex for topical delivery of oxymatrine. Arch Pharm Res 2011;34:
55162.
[88] Anurak L, Chansiri G, Peankit D, Somlak K. Griseofulvin solid lipid nanoparticles
based on microemulsion technique. Adv Mater Res 2011;197198:4750.
[89] Dabhi MR, Nagori SA, Sheth NR, Patel NK, Dudhrejiya AV. Formulation optimization of topical gel formulation containing micro-emulsion of terbinane hydrochloride with simplex lattice design. Micro Nanosyst 2011;3:17.
[90] Shah RR, Magdum CS, Patil SS, Niakwade NS. Preparation and evaluation of aceclofenac topical microemulsion. Iran J Pharm Res 2010;9:511.
[91] Khanna S, Katare OP, Drabu S. Lecithinised microemulsions for topical delivery of
tretinoin. Int J Drug Dev Res 2010;2:7119.
[92] Rozman B, Gosenca M, Gasperlin M, Padois K, Falson F. Dual inuence of colloidal
silica on skin deposition of vitamins C and e simultaneously incorporated in topical microemulsions. Drug Dev Ind Pharm 2010;36:85260.
[93] Yuan JS, Yip A, Nguyen N, Chu J, Wen XY, Acosta EJ. Effect of surfactant concentration on transdermal lidocaine delivery with linker microemulsions. Int J
Pharm 2010;392:27484.
[94] Campos Arajo LMP, Thomazine JA, Lopez RFV. Development of microemulsions
to topically deliver 5-aminolevulinic acid in photodynamic therapy. Eur J Pharm
Biopharm 2010;75:4855.
[95] Tsai YH, Lee KF, Huang YB, Huang CT, Wu PC. In vitro permeation and in vivo
whitening effect of topical hesperetin microemulsion delivery system. Int J
Pharm 2010;388:25762.
[96] Lopes LB, Van DeWall H, Li HT, Venugopal V, Li HK, Naydin S, et al. Topical delivery of lycopene using microemulsions: enhanced skin penetration and tissue antioxidant activity. J Pharm Sci 2010;99:134657.
[97] Saleem MA, Bansal A, Khalid S, Sadath A, Najmuddin M. Development of microemulsion based emulgel formulations of valdecoxib. Indian Drugs 2010;47:318.
[98] Bajpai M, Sharma PK, Mittal A. A study of oleic acid oily base for the tropical delivery of dexamethasone microemulsion formulations. Asian J Pharm 2009;3:
20814.
[99] Kitagawa S, Tanaka Y, Tanaka M, Endo K, Yoshii A. Enhanced skin delivery of
quercetin by microemulsion. J Pharm Pharmacol 2009;61:85560.
[100] Shishu G, Rajan S, Kamalpreet A. Development of novel microemulsion-based
topical formulations of acyclovir for the treatment of cutaneous herpetic infections. AAPS PharmSciTech 2009;10:55965.
[101] Peira E, Chirio D, Carlotti ME, Spagnolo R, Trotta M. Formulation studies of
microemulsions for topical applications of acyclovir. J Drug Deliv Sci Technol
2009;19:1916.
[102] Rozman B, Gasperlin M, Tinois-Tessoneaud E, Pirot F, Falson F. Simultaneous absorption of vitamins C and E from topical microemulsions using reconstructed
human epidermis as a skin model. Eur J Pharm Biopharm 2009;72:6975.
[103] Liu H, Wang Y, Lang Y, Yao H, Dong Y, Li S. Bicontinuous cyclosporin A loaded
water-AOT/tween 85-isopropylmyristate microemulsion: structural characterization and dermal pharmacokinetics in vivo. J Pharm Sci 2009;98:116776.
[104] Zhang P, Gao W, Zhang L, Chen L, Shen Q, Wang X, et al. In vitro evaluation of
topical microemulsion of capsaicin free of surfactant. Biol Pharm Bull 2008;31:
231620.
[105] Serdoz F, Voinovich D, Perissutti B, Grabnar I, Hasa D, Ballestrazzi R, et al. Development and pharmacokinetic evaluation of erythromycin lipidic formulations

[106]
[107]

[108]

[109]

[110]

[111]

[112]

[113]

[114]

[115]
[116]

[117]
[118]

[119]

[120]

[121]

[122]

[123]
[124]

[125]
[126]
[127]

[128]
[129]
[130]

[131]

[132]
[133]

313

for oral administration in rainbow trout (Oncorhynchus mykiss). Eur J Pharm

Biopharm 2011;78:4017.
Fan Y, Li X, Zhou Y, Fan C, Wang X, Huang Y, et al. Improved intestinal delivery
of salmon calcitonin by water-in-oil microemulsions. Int J Pharm 2011;416:32330.
Sun M, Zhai X, Xue K, Hu L, Yang X, Li G, et al. Intestinal absorption and intestinal
lymphatic transport of sirolimus from self-microemulsifying drug delivery systems assessed using the single-pass intestinal perfusion (SPIP) technique and a
chylomicron ow blocking approach: linear correlation with oral bioavailabilities in rats. Eur J Pharm Sci 2011;43:13240.
Setthacheewakul S, Mahattanadul S, Phadoongsombut N, Pichayakorn W,
Wiwattanapatapee R. Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats. Eur J
Pharm Biopharm 2010;76:47585.
Sharma G, Wilson K, van der Walle CF, Sattar N, Petrie JR, Ravi Kumar MNV.
Microemulsions for oral delivery of insulin: design, development and evaluation
in streptozotocin induced diabetic rats. Eur J Pharm Biopharm 2010;76:15969.
Yin YM, Cui FD, Mu CF, Choi MK, Kim JS, Chung SJ, et al. Docetaxel microemulsion
for enhanced oral bioavailability: preparation and in vitro and in vivo evaluation.
J Control Release 2009;140:8694.
Nornoo AO, Zheng H, Lopes LB, Johnson-Restrepo B, Kannan K, Reed R. Oral
microemulsions of paclitaxel: in situ and pharmacokinetic studies. Eur J Pharm
Biopharm 2009;71:3107.
Cheng MB, Jin W, Wang JC, Chen DW, Zhang Q. Preparation and in vitro characterization of oral microemulsions containing earthworm brinolytic enzyme.
Chin J New Drugs 2009;18:7883.
Cheng MB, Wang JC, Li YH, Liu XY, Zhang X, Chen DW, et al. Characterization of
water-in-oil microemulsion for oral delivery of earthworm brinolytic enzyme. J
Control Release 2008;129:418.
Li X, Yuan Q, Huang Y, Zhou Y, Liu Y. Development of silymarin self-microemulsifying
drug delivery system with enhanced oral bioavailability. AAPS PharmSciTech
2010;11:6728.
Shen Q, Li X, Yuan D, Jia W. Enhanced oral bioavailability of daidzein by
self-microemulsifying drug delivery system. Chem Pharm Bull 2010;58:63943.
Lu JL, Wang JC, Zhao SX, Liu XY, Zhao H, Zhang X, et al. Self-microemulsifying drug
delivery system (SMEDDS) improves anticancer effect of oral 9-nitrocamptothecin
on human cancer xenografts in nude mice. Eur J Pharm Biopharm 2008;69:
899907.
Andersson M, Greiff L, Wollmer P. Effects of a topical microemulsion in house
dust mite allergic rhinitis. Basic Clin Pharmacol Toxicol 2011;108:1468.
Sintov AC, Levy HV, Botner S. Systemic delivery of insulin via the nasal route
using a new microemulsion system: in vitro and in vivo studies. J Control Release 2010;148:16876.
Shahiwala A, Dash D. Preparation and evaluation of microemulsion based formulations for rapid-onset intranasal delivery of zonisamide. Adv Sci Lett 2010;3:
4426.
Piao HM, Balakrishnan P, Cho HJ, Kim H, Kim YS, Chung SJ, et al. Preparation and
evaluation of fexofenadine microemulsions for intranasal delivery. Int J Pharm
2010;395:30916.
Kumar A, Sharma P, Chaturvedi A, Jaiswal D, Bajpai M, Choudhary M, et al. Formulation development of sertraline hydrochloride microemulsion for intranasal
delivery. Int J ChemTech Res 2009;1:9417.
Yao J, Hou L, Zhou JP, Zhang ZQ, Sun L. Preparation of lorazepam-loaded microemulsions for intranasal delivery and its pharmacokinetics. Pharmazie 2009;64:
6427.
Peng CC, Bengani LC, Jung HJ, Leclerc J, Gupta C, Chauhan A. Emulsions and
microemulsions for ocular drug. J Drug Deliv Sci Technol 2011;21:11121.
El Maghraby GM, Bosela AA. Investigation of self-microemulsifying and microemulsion systems for protection of prednisolone from gamma radiation. Pharm
Dev Technol 2011;16:23742.
Kapoor Y, Chauhan A. Ophthalmic delivery of cyclosporine A from Brij-97 microemulsion and surfactant-laden p-HEMA hydrogels. Int J Pharm 2008;361:2229.
Date AA, Nagarsenker MS. Parenteral microemulsions: an overview. Int J Pharm
2008;355:1930.
Jain J, Fernandes C, Patravale V. Formulation development of parenteral
phospholipid-based microemulsion of etoposide. AAPS PharmSciTech 2010;11:
82631.
Kale AA, Patravale VB. Development and evaluation of lorazepam microemulsions for parenteral delivery. AAPS PharmSciTech 2008;9:96671.
Hu CJ, Zhao XL, Li JZ, Kang SM, Yang CR, Jin YH, et al. Preparation and characterization of -elemene-loaded microemulsion. Drug Dev Ind Pharm 2011;37:76574.
Yin Y, Cui F, Mu C, Chung SJ, Shim CK, Kim DD. Improved solubility of docetaxel
using a microemulsion delivery system: formulation optimization and evaluation. Asian J Pharm Sci 2009;4:3319.
Leclercq SY, Marques Dos Santos RM, Macedo LB, Campos PC, Ferreira TC, De
Almeida JG, et al. Evaluation of water-in-oil-in-water multiple emulsion and
microemulsion as potential adjuvants for immunization with rabies antigen.
Eur J Pharm Sci 2011;43:37885.
Sharma A, Arora S, Grewal P, Dhillon V, Kumar V. Recent innovations in delivery
of articial blood substitute: a review. Int J Appl Pharm 2011;3:15.
Dantas TNC, Silva HSRC, Neto AAD, Marcucci MC, Maciel MAM. Development of a
new propolis microemulsion system for topical applications. Braz J Pharmacogn
2010;20:36875.