Review Article

Topical Emulgel: Basic Considerations in Development and

Advanced Research
S. MALAVI1, P. KUMBHAR2*, A. MANJAPPA2, S. CHOPADE2, O. PATIL2, UDICHI KATARIA3, J. DWIVEDI4 AND J. DISOUZA2
Department of Pharmaceutics, Pacific Academy of Higher Education and Research, Udaipur, Rajasthan 313001,
1
Department of Pharmaceutics, Genesis Institute of Pharmacy, Sonyachi Shiroli, Radhanagari, Kolhapur,
Maharashtra 416212, 2Department of Pharmaceutics, Tatyasaheb Kore College of Pharmacy, Warananagar, Panhala, Kolhapur,
Maharashtra 416113, 3Geetanjali Institute of Pharmacy, Geetanjali University, Udaipur, Rajasthan 313001, 4Pacific
College of Pharmacy, Pacific University, Udaipur, Rajasthan 313001, India

Malavi et al.: Emulgel Basic Consideration and Advanced Research

Emulgel is a promising drug delivery strategy that has gained popularity in recent years for topical
delivery of hydrophobic drugs. Emulgel is an emulsion that is gelled by mixing it with gelling agents. It is
an interesting topical drug delivery system as it has a dual release control system, i.e., gel and emulsion.
Emulgel has several favorable properties for dermatological use such as being thixotropic, greaseless,
easily spreadable, easily removable, emollient, nonstaining, long shelf life, transparent and pleasing
appearance. Despite, many advantages of the emulgel, the disadvantages include low permeability, poor
pharmacokinetics and pharmacodynamics performance; therefore an advanced concept nanoemulgel
came into the existence. Regardless of having few limitations, nanoemulgel formulation can be considered
as impending and promising candidates for topical delivery of lipophilic drugs in the future. To know
the potential of emulgel as a delivery vehicle, the present review offers a comprehensive overview on the
rationale behind the use of emulgel, formulation considerations and characterization of emulgel and
advanced research in the emulgel. Furthermore, we have summarized and discussed the outcome of different
in vitro and in vivo studies of emulgel or nanoemulgel. Finally, the major challenges of nanoemulgel drug
delivery system, patented and marketed emulgel or nanoemulgel formulations have been discussed. Based
on the studies covered in this manuscript, it was understood that emulgel or nanoemulgel has emerged as
an optimistic approach in the topical delivery of hydrophobic drugs to improve solubility, permeability
and bioavailability, and reduce toxicities.
Key words: Emulgel, nanoemulgel, topical drug delivery, incompatibility, evaluations, patents, therapeutic
window

Topical drug administration is a localized drug delivery many disadvantages such as sticky nature, lack of
system, through various routes such as ophthalmic, spreadability, stability issues, etc., ultimately leading
rectal, vaginal and skin, anywhere in the body. Topical to patient non-compliance. The aforementioned
preparations are chiefly utilized topically to achieve drawbacks have encouraged the use of transparent
localized effects at the site of their application[1]. This gels or hydrogels in cosmetics and pharmaceutical
route is most preferred in the treatment of a variety of preparations due to their less sticky nature, better
skin disorders such as acne, eczema, psoriasis, etc. The spreading coefficient and dissolution, greater patient
topical formulations offer an array of benefits such as compliance and improved efficacy. Gels are a relatively
prevention of pre-systemic metabolism, augmented new class of dosage form created by trapping large
bioavailability and therapeutic response, improved amounts of aqueous or hydroalcoholic liquid in a
patient compliance, ease of administration, reduced colloidal solid particle network that may consist
gastrointestinal tract incompatibility[2]. Moreover, of inorganic substances, such as aluminum salts or
topical formulations are highly appropriate for the natural or synthetic organic polymers[6]. However,
delivery of cargo with a narrow therapeutic window[3].
This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which
The different kinds of topical drug delivery systems allows others to remix, tweak, and build upon the work non-commercially,
used for the treatment of skin-related diseases include as long as the author is credited and the new creations are licensed under
the identical terms
emulsions, creams, ointments, lotions, powders,
etc.[4,5]. These delivery systems are associated with Accepted 06 September 2022
Revised 07 December 2021
Received 10 March 2020
*Address for correspondence
Indian J Pharm Sci 2022;84(5):1105-1115
E-mail: [email protected]
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beneficial gels show a significant disadvantage in the weight, partition coefficient and degree of ionization of
delivery of hydrophobic therapeutics. It is reported drug also have a great impact on topical absorption of
that approximately 40 % of new chemical entities are the drug[10].
hydrophobic and the delivery of these poorly water-
soluble drugs is a big challenge. Therefore, to cover EMULGEL
up this deficiency, emulgel a new approach that came Emulgel is just a mixture of gels and emulsions.
into existence. Emulgel is a mixture of emulsion and Emulgel is emulsions, either o/w or w/o, which are
gel base. gelled by combining with a gelling agent. Emulgel is
Most of the naturally obtained or synthesized drugs more effective in curative aspects than regular gel. The
are Biopharmaceutical Classification System (BCS) conversion of an emulsion into the gel is accountable
class II drugs[7,8]. They possess low solubility and high for improved stability and penetrability of emulsion[11].
permeability. The low solubility of the drug affects the Moreover, this system exhibits dual control release
dissolution rate and extent of drug absorption and their which is attributed to both emulsion and gel. However,
permeation through the membrane and bioavailability. the stability and release of incorporated drugs in
Therefore, Nanoemulgel (NEG) is one of the important emulgel are affected by the type and concentration
strategies that can be used for the topical delivery of of gel-forming polymer. Emulgel also prolongs the
a hydrophobic drug. In the NEG, nanoemulsion is contact period of medication over the skin owing to
incorporated into the gel base. The nanoemulsion its mucoadhesive property. In addition, this system
causes improved solubility of the hydrophobic drugs. is capable to prevent a dangerous inconvenience that
In addition, the nanoemulsion of NEG is accountable arises from intravenous administration of drugs and
for augmenting the skin permeability of cargo owing variations in the absorption of the drug at different
to finely distributed droplets of nanoemulsion. Thus, physiological conditions when administered via the
the NEG offers easy permeation of cargo through the oral route. Other various advantages of emulgel include
skin to deliver it into the blood thereby improving the easy incorporation of hydrophobic drugs, augmented
pharmacokinetic and pharmacodynamics performance drug loading capacity, production feasibility (simple
of the drugs. The hydrophobic drug is commonly and short processing steps) and low preparation cost,
entrapped in oil-in-water (o/w) emulsion whereas avoidance of first-pass metabolism and gastrointestinal
hydrophilic drugs are entrapped in the water-in-oil incompatibility, improved patient compliance,
(w/o) emulsion[9]. suitability for self-medication, narrow therapeutic
window and selective to a specific site. Despite the
Through this manuscript, an attempt has been made
aforementioned advantages, emulgel allied with
to broadly review the emulgel as an efficient approach
certain disadvantages like difficulty to absorb large size
in topical drug delivery. The areas covered in this
particle through the skin, poor permeability of drugs,
review include the rationale behind the use of emulgel,
bubble formation during the emulgel preparation and
formulation considerations, manufacturing and
skin irritation or allergic reactions[12].
characterization of emulgel. Furthermore, NEG as an
advanced topical delivery approach for hydrophobic RATIONALE BEHIND USE OF EMULGEL
drug, packaging of emulgel, patented and marketed
formulations are also discussed. We conclude by The commonly used topical formulations such as
outlining future perspectives for the development of ointment, cream, lotion, etc., have many drawbacks,
emulgel. including stickiness causing patient irritation when
applied, lower coefficient of spreading and need to be
FACTORS AFFECTING TOPICAL applied with rubbing. They also exhibit a stabilization
ABSORPTION OF THE DRUG problem. Because of the aforementioned disadvantages
of the large group of semisolid preparations, the use of
The physiological and physicochemical factors play
transparent gels has increased in cosmetics as well as in
an imperative role in the topical absorption of the
pharmaceutical preparations. The gel is colloid, which
drug. The physiological factors that show influence on
is normally 99 % liquid, which is immobilized by the
retention of the topically applied drug include skin pH
surface tension between the gel and the macromolecular
and thickness, hydration of the skin, the sweat glands
fiber network created by a small amount of gelling
density, amount of blood flow and inflammation.
material present. In the present scenario, more
Similarly, the physicochemical factors like molecular
than 40 % of therapeutically active compounds are
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hydrophobic and the handling of hydrophobic drugs is Aqueous material:
a major limitation of gel. The emulsion-based gel is an
approach that can successfully incorporate and deliver This forms the aqueous phase of the emulsion. In the
a hydrophobic therapeutic moiety with improved presence of the gelling agent, this aqueous phase is
solubility and penetrability through the skin. Moreover, accountable for the conversion of emulsion form into
the emulgel can cause substantial improvement in the emulgel. Commonly used aqueous materials are
the pharmacological action and reduction in the dose water and alcohols[21].
of the drug due to significant penetration of emulgel Oils:
globules in soft tissues[13]. There has been a great deal
of interest in recent years in the use of novel polymers An emulsion is the primary part of the emulgel. The
with complex functions as emulsifiers and thickeners. selection of type and quantity of oil as one of the phases
The gelling ability of these compounds allows stable of the emulsion is mainly allied with the eventual use of
emulsions and creams to be produced by reducing the emulgel. Moreover, this oil phases chiefly influence the
surface and interfacial stress, as well as increasing the viscosity, permeability and stability of the emulsion. In
aqueous phase viscosity[13,14]. the selection of oil phase, it is essential to ensure that
the oil is pure and free of unpleasant and unsaponifiable
FORMULATION CONSIDERATIONS constituents like free radicals, peroxides, sterols
In the formulation of topical emulgel, it is essential and polymers. Numerous such types of unwanted
to evaluate emulgel for its non-toxic, non-irritating, constituents can be produced during storage causing
non-comedogenic and non-sensitizing properties. the deterioration of the oil phase and that results in
Furthermore, formulating cosmetically elegant and unstable formulation[12,21].
biocompatible emulgel is of vital importance. The Mineral oils alone or mixed with soft or hard paraffin,
aforementioned properties of emulgel are chiefly are commonly used as the carrier as well as for its
associated with formulation excipients used. Thus, the occlusive and sensory properties, for externally applied
formulation considerations assume an imperative role emulsions. Non-biodegradable mineral and castor oils,
in the emulgel[15-20]. which have a local laxative effect are widely used oils
in oral preparations. The fish liver oils or various fixed
Drug: oils of vegetable origin (e.g., Arachis, cotton and maize
The absorption of the drug through the skin is chiefly oils) are used as nutritional complements[12].
influenced by the properties of the drug. These kind of Emulsifiers:
physicochemical and biological properties of drugs play
an imperative role to formulate them into emulgel for Emulgel is a gelled emulsion prepared by using a suitable
topical or transdermal applications. The drug candidate gelling agent. An emulsion is a thermodynamically
suitable to formulate as an emulgel should possess’ unstable system that can be made stable by the addition
high pKa value, Half-life (t1/2) of less than 10 h, less of appropriate emulsifying agents. The emulsifying
molecular size, the molecular mass of 500 daltons or agents are chiefly accountable for reducing the
less, partition coefficient (logP) value of 0.8 to 5 and interfacial tension that causes augment in the stability
less polarity. In addition, the drug candidate should be of the emulsion. The emulsifying agent selected should
non-irritating with a skin permeability coefficient of possess good Hydrophilic-Lipophilic Balance (HLB)
equal to or more than 0.5×10-3 cm/h[3]. and yield stable emulsion. Furthermore, the stability
of emulsion is mainly allied with type and quantity of
Vehicle: emulsifying agent used to make emulsion. Generally,
The vehicle used in the formulation of emulgel also the emulsifying agents with HLB of less than 8 are
assumes a vital role in the absorption of the drug utilized to prepare w/o type of emulsion while those
through the skin. The vehicle used for the preparation with HLB of more than 8 are used to make o/w type of
of emulgel should possess properties like efficient emulsion[12].
deposition of the medication with even distribution Emulsifying agents are used both at manufacturing
on the skin; deliver and release the drug at the site of time to facilitate emulsification and during shelf-life
operation; sustaining a level of therapeutics in the target to maintain stability. Polyethylene glycol 40 stearate,
tissue for a sufficient period. Furthermore, it should be sorbitan monooleate (Span 80), polyoxyethylene
compatible with the skin of the patient[3].
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sorbitan monooleate (Tween 80), stearic acid and enhancer. Therefore, there is a necessity to optimize
sodium stearate are widely used as emulsifiers[3,12]. the type and concentration of these agents to achieve
better transdermal delivery of the drug. The penetration
Gelling agents: enhancers used in the emulgel should possess low
Gelling (cross-linking) agents are key components of irritancy, toxicity and better penetrability. These
the emulgel used to make a system thixotropic. They agents facilitate drug absorption through different
are primarily used as a thickening agent to improve the mechanisms such as temporarily interrupting the
texture as well as dosage form quality. The sort of gelling skin barrier, fluidizing the lipid channels between
agent used and its concentration has great influence on corneocytes; altering the partitioning of the drug into
the drug release and stability of emulgel. For instance, skin structures, etc.,[12].
the emulgel prepared using Hydroxy Propyl Methyl As a penetration enhancer, oleic acid, lecithin,
Cellulose (HPMC) as a gelling agent have been reported isopropyl myristate, linoleic acid, clove oil, menthol
to show better drug release when compared to emulgel and eucalyptus oil, Myrj™, Transcutol® P, cineol, etc.,
prepared using Carbopol polymers[8]. Furthermore, can be used[23].
various studies have reported inversely proportional
relationship between the concentration of gelling agent METHODS OF PREPARATION
and drug release from the emulgel. The combination of
The simple method used for the preparation of emulgel
gelling agents was also found to augment the stability
includes three main steps. The first two steps are the
of emulgel[22].
formulation of emulsion and gel base separately
Various kinds of gelling agents used in the emulgel followed by incorporation of an emulsion into gel base
preparation include natural, semi-synthetic and that leads to the formation of emulgel. The fundamental
synthetic. However, the chief shortcoming associated steps in the emulgel preparation are shown in fig. 1.
with natural gelling agents is their high susceptibility In the emulsion formulation, initially, aqueous phase
towards microbial degradation. Therefore, semi- is prepared by dissolving hydrophilic surfactant or
synthetic and synthetic gelling agents are found to be emulsifying agents like Tween 20 into distilled water.
widely used nowadays in emulgel preparation[12]. The Similarly, the oil phase is prepared by dissolving
extensively used gelling agents in the preparation of lipophilic surfactant or emulsifying agents like Span 20
emulgel are Carbopol 934, Carbopol 940, HPMC 2910, into oil (liquid paraffin). Both aqueous and oil phases
HPMC, Carboxy Methyl Cellulose (CMC) sodium and are heated separately at a temperature of 70°-80° and
poloxamer 407[3]. then both phases are blended together with constant
stirring, resulting in an emulsion. The gel phase is
Penetration enhancers: prepared by dispersing gelling agents like Carbopol or
These agents are primarily used to advance the HPMC) into distilled water. Finally, the emulsion and
transdermal delivery of the drug. The penetration of a gel phase are mixed together in the ratio of 1:1 with
drug from an emulgel can be significantly influenced gentle stirring that leads to the formation of emulgel[24].
by the type and concentration of the penetration

Fig. 1: Fundamental steps in the preparation of emulgel

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Another method described for emulgel formulation viscometer. The maximum shear rate used is 100 rpm
involves several steps such as dispersion of polymer while a minimum shear rate is 10 rpm[26-28].
in aqueous phase and its neutralization and oil phase
emulsification. Initially, the polymer is dispersed in Globule size and size distribution in emulgel:
deionized water and stirred continuously at suitable Globule size and size distribution are determined by the
speed and duration at room temperature. The resulting Malvern Zetasizer. 1.0 g sample is dissolved in purified
dispersion is then neutralized by the addition of Sodium water and agitated to get homogeneous dispersion.
hydroxide (NaOH) solution that leads to the formation The sample is then injected into the photocell of
of stable gel via polymer chains distension. The gel is Zetasizer[26-28].
then stored at 4° for 24 h that causes the entire hydration
of polymer gels. Finally, the oil phase is added into the Drug content determination:
polymer gel with continuous stirring that result in the
The drug content in emulgel is measured by dissolving
formation of emulgel[25].
the known quantity of emulgel in a suitable solvent
EVALUATION OF EMULGEL like ethanol by sonication. The resulting solution is
then filtered and absorbance is measured after suitable
Physical appearance: dilution at the maximum wavelength of drug-using
Ultraviolet-Visible (UV/Vis) spectrophotometer[26-28].
The prepared emulgel formulations are visually
inspected for color, homogeneity, consistency and Swelling index:
pH. A pH meter (Digital pH meter 115 pm) is used to
calculate the pH values of 1 % aqueous solutions of the The swelling index is determined by taking 1 g of gel
prepared gellified emulsion[26-28]. on porous aluminum foil and then placed separately in
a 50 ml beaker containing 10 ml 0.1 N NaOH. Then
Spreading coefficient: the samples are removed from beakers at different time
intervals and put on dry place for some time after it
The spreading coefficient is determined by the apparatus
reweighed[26-28]. Swelling index is calculated using the
suggested by Mutimer. It consists of a wooden block,
following formula
which is attached to a pulley at one end. The spreading
coefficient is measured based on ‘Slip’ and ‘Drag’ Swelling Index (SW) %=[(Wt–Wo)/Wo]×100
characteristics of emulgel. A ground glass slide is fixed Where, (SW) %=Equilibrium percent swelling;
on the wooden block. An excess of emulgel (about 2 g) Wo=Original weight of emulgel at zero time after time t
under study is placed on this ground slide. The emulgel and Wt=Weight of swollen emulgel.
preparation is then sandwiched between this slide and
the second glass slide having the same dimension as In vitro release study:
that of the fixed ground slide. The second glass slide is
Franz diffusion cell is used for drug release studies.
provided with the hook. A weight of 500 mg is placed
Gellified emulsion approximately (200 mg) is applied
on the top of the two slides for 5 min to expel air and to
onto the surface of the egg membrane evenly. The
provide a uniform film of the emulgel between the two
egg membrane is clamped between the donor and the
slides. The measured quantity of weight is placed in the
receptor chamber of the diffusion cell. The receptor
pan attached to the pulley with the help of a hook. The
chamber is filled with freshly prepared Phosphate
time (s) required by the top slide to cover a distance
Buffered Saline (PBS) (pH 5.5) solution to solubilize
of 5 cm is noted. A shorter interval indicates a better
the drug. The receptor chamber is stirred by a magnetic
spreading coefficient[26-28]. It is calculated using the
stirrer. The samples (1.0 ml aliquots) are collected at a
below formula
suitable time interval and are analyzed for drug content
S=M×L/T by UV visible Spectrophotometer after appropriate
Where, M=Weight tied to upper slide; L=Length of dilutions. The cumulative amount of drug released
glass slides and T=Time taken to separate the slides. across the egg membrane is determined as a function
of time[26-28].
Rheological study:
Antimicrobial assay:
The viscosity of the developed emulgel formulations is
determined by using a cone and plate type of Brookfield The antimicrobial assay is used for both qualitative as

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well as quantitative estimation of antimicrobial agents Pharmacokinetic study:
using the microorganisms. This assay can be carried
out by using the agar well diffusion or ditch plate The pharmacokinetic study is performed for those
technique. In the agar well diffusion technique, initially, emulgel formulations which show systemic absorption
the agar plates are prepared using a sterile nutrient on transdermal applications. The animals like rats are
agar medium. These plates are then inoculated with a used to assess the various pharmacokinetic parameters
specific quantity of 24 h broth culture. Then the cavities such as peak plasma concentration (Cmax), the time
of 8 mm in diameter are prepared on the agar plates to reach Cmax (Tmax), the total Area Under the Curve
via a sterile borer. The test formulations (fixed volume) (AUC0-∞). To estimate the aforementioned parameters,
are then added into each cavity separately. Finally, all the blood sample is collected from the animal via the
the plates are incubated for 24 h-48 h at 37° and the retro-orbital vein after a specific time interval on topical
diameter of the zone of inhibition in mm is measured[24]. administration. The samples are then centrifuged at 15
000 rpm for 10 min at 4° temperature. The separated
In the case of the ditch plate technique, the ditch is plasma (100 μl) is then mixed with acetonitrile (1
prepared in the plate containing media and then the test ml) which causes protein precipitation. Further, the
formulation is placed in a ditch. The loopful of fresh samples are centrifuged again at 15 000 rpm, 4° for 5
culture is then streaked across the agar at a right angle min and the supernatant (20 μl) is collected. Finally,
from the ditch to the edge of the plate. Finally, the plates the sample is analyzed using High-Performance Liquid
are incubated at 25° for 18 h-24 h and the percentage Chromatography (HPLC)[31].
inhibition is calculated using the following formula[29]
Stability study:
% Inhibition=L2/L1×100
Where, L1=Total length of the streaked culture and The stability study of emulgel is performed according
L2=Length of inhibition to International Council on Harmonization (ICH)
guidelines. Briefly, the emulgel formulations are
Skin irritation test: packed in collapsible tubes made up of aluminum.
Then these tubes are stored at different temperatures
Skin irritation studies are performed by both in vitro and relative humidity such as 5°, 25°/60 % RH, 30°/65
and in vivo methods. This study is chiefly carried out % RH and 40°/75 % RH for 3 mo. During the storage,
to evaluate the tolerability of the emulgel components the formulations are withdrawn after a particular time
after the topical application. In the case of in vitro skin interval (15, 30, 60 and 90 d) and can be subjected for
irritation study, Hen’s Egg-Chorioallantoic Membrane evaluation of physical appearance, viscosity, pH, drug
(HET-CAM), an Organisation for Economic Co- content and in vitro drug release, etc.,[29].
operation and Development (OECD) recommended
test is used. In this technique, freshly layed hen eggs NEG AS AN ADVANCED APPROACH IN
with developed chick embryos are used and the TOPICAL DRUG DELIVERY
irritation behavior of test formulation on chick embryo
is studied[30]. NEG is an advanced approach employed in the topical
delivery of hydrophobic drugs. In the NEG, the
On the other hand, various studies reported the use of nanoemulsion is mixed with a gelling agent. Nowadays,
rabbits or rats to perform the in vivo skin irritation test. most of the researches are intensified on NEG-based
The skin of the rat or rabbit (4 cm2) is shaven prior transdermal delivery of hydrophobic drugs. The clinical
to beginning of the study. Then developed emulgel applications of various conventional dosage forms such
formulation (specific dose) is applied on the shaven as creams, ointments, gels, emulsion and emulgel are
dorsal side at a definite area of the animal skin. At limited because of poor drug permeability through the
the end of 24 h, animals are examined for any signs skin due to large particle size. Therefore, to overcome
of irritation. Any skin irritation, such as erythema or the permeability problem, the NEG concept came into
edema is noted in the animals and a score is assigned[24]. existence.
Various other in vivo animal studies performed for Nanoemulsion in NEG is a nano sized solvent droplet
emulgel may relate to the category of drug incorporated stabilized with the use of surfactants that do not require
into the emulgel and ultimate use of the developed penetration enhancers[32]. A large number of studies
system. This test may include anti-inflammatory reported improved skin permeation of drugs from
activity, anti-fungal activity, etc.,[24]. nanoemulsions than conventional emulsions, gels,
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creams and ointments . The improved permeability
[33,34]
An ample of studies proved the improved
of drugs from nanosized topical formulations might be pharmacokinetic and pharmacodynamics performance
due to lipid bilayer disruption which is evident from of drugs from NEG. Aparna et al.[31], have fabricated
the distinct void and empty spaces in the nanoemulsion telmisartan-loaded NEG with improved solubility and
treated skin samples and drug extent retention at the permeability via topical administration. They found
site of action[35,36]. Despite, the many advantages of substantial improvement in the bioavailability of
nanoemulsion, its topical applications are limited due telmisartan from a NEG when compared to the normal
to its low viscosity and spreadability and stability[37]. gel in vivo in rats. The telmisartan NEG has displayed
significant (p<0.01) improvement in the area under
The aforementioned drawbacks of nanoemulsion can
the plasma concentration-time curve to infinity time
be conquered by the incorporation of nanoemulsion
(AUC∞-1) value (334.37 mg.h/ml) when compared to
into a gelling system. NEG is chiefly an emulsion-based
the normal gel (221.08 mg.h/ml). Furthermore, the
topical gel formulation, where nanosized emulsion
peak plasma concentration of telmisartan was found to
globules are further converted into NEG by adding a
be more from NEG (6.2 µg/ml) than normal gel (5.7
suitable gelling agent. Some biocompatible gelling
µg/ml). They concluded that substantial improvement
agents such as Carbomer 934, Carbomer 940, Carbomer
in the bioavailability of telmisartan from the NEG
980, pluronic, xanthan gum and carrageenan have
might be due to the augment in permeability via
been identified which is compatible with surfactants
disturbing the cell membrane. Furthermore, augment in
and can modify the viscosity of nanoemulsion[38].
the bioavailability might be attributed to the improved
The various advantages of NEG include improved
lymphatic absorption owing to the presence of long-
patient compliance due to their non-greasy and non-
chain oils[36]. Jeengar et al. investigated curcumin-
irritant property, better drug release, high drug-loading
loaded NEG using emu oil to improve the permeability
capacity, increased permeability and low skin irritation.
and anti-inflammatory activity in the treatment of
Currently, formulation scientists are developing NEG for
rheumatoid arthritis. The NEG displayed momentous
delivery via different routes such as transdermal, dental,
(higher in terms of inhibition of rat paw edema 66 %)
vaginal, ocular, nose to the brain for the treatment
anti-inflammatory activity of curcumin NEG when
of various local as well as systemic ailments[38,39]. The
compared to the normal curcumin gel (14.22 %)[37].
drug loaded emulgel and NEG prepared using different
Similarly, Srivastava et al. have developed ketoprofen-
gelling agents exhibiting significant improvement in
loaded in situ NEG for the treatment of periodontitis.
the physicochemical properties and, in vitro and in vivo
This NEG demonstrated sustained in vitro release and
performance are summarized in Table 1[17,40-53].
reduced toxicity of ketoprofen[54].

TABLE 1: EMULGEL AND NEG WITH IMPROVED IN VITRO AND IN VIVO PERFORMANCE
Drug Gelling agent Significance
NEG showed significantly higher cumulative amphotericin B permeation (999.81±7.3 mg)
Amphotericin B Carbopol
than a solution (254.161±1.45 mg) and nanoemulsion (870.42±4.2 mg) after 24 h[38]
The skin permeation potential of atorvastatin was significantly (p<0.05) augmented by NEG.
Atorvastatin CMC In vivo wound healing studies in rats exhibited the highest percent of wound contraction by
atorvastatin from NEG [40]
Chlorphenesin HPMC Remarkably improved drug release and antifungal activity[41]
NEG exhibited significantly improved anti-inflammatory activity by inhibiting the
Curcumin Carbopol 940
phosphorylation of IKK-α[37]
Cyclosporine Guar gum Significantly (p<0.05) augmented permeation of cyclosporine from NEG than gel[42]
Carbomer Significantly enhanced (p<0.01) permeability of eprinomectin from NEG and emulgel by
Eprinomectin
940 8.07 fold and 5.57 fold respectively than suspension[43]
J flux and permeability coefficient of emulgel is found to be 0.2301(mg/cm2/h) and
Itraconazole Carbopol 934
0.001151(Kp) which is similar to marketed formulation[44].
Itraconazole Xanthan gum Emulgel showed promising results of spreadability; extrudability, itraconazole content and release[45]
The emulgel showed good spreadability, homogeneity, stability and smoothening effect. It
Ketoconazole Carbopol 934
also exhibited improved skin penetration of ketoconazole[46]
Ketoconazole Carbopol 934 Emulgel showed sustained ketoconazole release in a controlled manner than cream[47]
Carbopol
Ketoprofen NEG demonstrated sustained release of ketoprofen into the periodontal pocket[17]
934P

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Exhibited acceptable physical properties, pH, drug content, viscosity and stability. It also
Luliconazole Carbopol 934
displayed momentous antifungal activity[48]
Carbopol 940 gives a smooth texture and acceptable viscosity for mucosal administration.
Mentha
Carbopol 940 The emulgel showed better stability over 90 d and improved the effectiveness of mentha
essential oil
essential oil against candidiasis like condition[49]
Carbomer NEG displayed a significantly (p<0.05) augmented permeation and flux of piroxicam than
Piroxicam
934 marketed formulation[35]
Emulgel showed substantially augmented penetration of tolnaftate in fungi cells that result
Tolnaftate Carbopol 940
in remarkable antifungal activity[50]
NEG exhibited substantially improved permeability of terbinafine through the skin, and
Terbinafine Carbopol 934
increased physical stability[51]
Significantly (p<0.05) improved skin permeation from formulated emulgel than the
Terbinafine HCl Carbopol 940
commercial emulgel[52]
Ex vivo permeation studies demonstrated that the NEG significantly enhanced the tenofovir
Tenofovir HPMC
permeation by 39.65-fold, with a cumulative amount of 1866.54±108.62 μg.cm-2[53]

In another study, Mohamed et al. have developed availability of inadequate types of surfactants and co-
NEG for topical delivery of atorvastatin against surfactant for nanoemulsion preparation. Furthermore,
wound healing. This NEG exhibited significant NEG formulations are unable to deliver large size
(p<0.05) permeation of atorvastatin through the skin. drug molecules with an average molecular weight of
In addition, the NEG displayed remarkable wound more than 400 Da through the skin. Most of the gelling
healing potential in vivo in the Wistar rats[40]. Begur agents used in NEG preparations are highly pH and
et al. have designed cyclosporine-loaded NEG with temperature-sensitive. In addition, another challenge
improved permeability via transdermal application. The allied with NEG preparation is the incorporation of
NEG demonstrated significantly (p<0.05) augmented nanoemulsion into the gel. Low stirring homogenization
permeation and flux in vivo in rats[42]. Furthermore, speed cannot produce a uniform or homogenate
Yujuan et al. investigated NEG for transdermal mixture, whereas, excess stirring speed cause cracking
delivery of eprinomectin against endoparasites and of the gel[21,38].
ectoparasites. They studied the permeability behavior
of eprinomectin-loaded NEG and emulgel and were PACKAGING OF EMULGELS
compared with suspension. Both NEG and emulgel Packaging of emulgel is usually done in membrane-
loaded with eprinomectin exhibited momentous sealed lacquered aluminum tube with an inner coating
permeability 8.07 and 5.57 folds respectively than of a phenoxy-epoxy based lacquer closed with a
eprinomectin suspension revealing better absorption of propylene screw cap or aluminum laminated tubes
cargo from NEG[43]. In another study, Dhawan et al. have closed by a molded seal, with a propylene screw cap
fabricated NEG for transdermal delivery of piroxicam (Public Assessment Report of Voltaren Emulgel).
with improved permeability and reduced skin irritation. These laminate tubes give the benefit of aluminum
This NEG displayed significantly (p<0.05) improved tube properties with the appearance of plastic. The new
permeability of piroxicam from NEG[35]. generation of laminate tubes uses modern technology
NEG DRUG DELIVERY CHALLENGES to produce the tube with maximum space for graphics.
Laminate material prevents the transfer of light, air
Despite distinct advantages, some challenges and moisture. It consists of two layers, an aluminum
associated with the NEG drug delivery system are the layer providing integrity and shelf appealing plastic
high energy requirement for nanoemulsion preparation tubes. The protective barrier serves various functions
and stability of nanoemulsion. Though, low-energy as they provide high gloss protective lacquer, a resistant
methods exist, but are not perfectly appropriate for barrier for products requiring maximum compatibility
large-scale manufacturing and normally need higher along with the flavor and fragrance protection with the
amounts of surfactants. However, a high amount reduced absorption[55].
of surfactant use causes skin irritation and contact
dermatitis. Sometimes, NEG was reported to show Material for laminates tubes:
allergic reactions on the skin. Moreover, the critical step Foil laminates: Foil laminates provide a barrier against
to provide adequate stability of the NEG formulation is light, air and moisture. It reduces the absorption of
a selection of the proper type and amount of surfactants aroma (flavor and fragrance). Besides, it has aluminum
and co-surfactants[21]. Another important concern is the
1112 Indian Journal of Pharmaceutical Sciences September-October 2022
 www.ijpsonline.com
properties with the look and feel of plastic. chiefly employed in the treatment of fungal and
bacterial infections, skin rashes, skin inflammation and
All plastic laminates: It has a chemical-resistant
pains. In addition, it is also recommended in hormonal
barrier. It helps to retain the shape and form, and offers
conditions, immune problems, arthritis, etc. Diclomax
the plastic like appearance and feel. It has both an
emulgel is composed of diclofenac sodium and is
opaque and transparent appearance.
used in the treatment variety of conditions such as
PATENTED AND MARKETED EMULGEL rheumatism, osteoarthritis of the spine and peripheral
FORMULATION joints. Kleraderm Gaia 480 emulgel is employed as
a vaginal antiseptic formulation. Moreover, Isofen
Various patented emulgel and NEG formulations emulgel is loaded with Nonsteroidal Anti-Inflammatory
loaded with different drugs for the treatment of diverse Drug (NSAID) ibuprofen. It is found to be useful for
type of diseases via the transdermal route are presented the treatment of rheumatic and other muscular pains.
in Table 2. Furthermore, some commercially available Cataflam emulgel marketed by Novartis Alcon is
emulgel formulations in the market are represented in composed of diclofenac diethyl ammonium and is used
Table 3. Voltren emulgel is composed of a diclofenac in the treatment of inflammation and swelling in the
diethyl ammonium which is used to relieve back, neck joints and muscles, pain, osteoarthritis, etc.,[3,12].
and shoulder pain and reduce swelling. Miconaz-H-
emulgel is marketed by Medical Union Pharmaceutical CONCLUSIONS AND FUTURE
which contains miconazole nitrate and hydrocortisone PERSPECTIVES
as Active Pharmaceutical Ingredients (APIs). It is

TABLE 2: PATENTED EMULGEL FORMULATIONS

Patent no Application no Title of patent Inventors Year
Caillet-Bois, Isabelle Rault and
EP2214642 A1 EP20080844931 Topical composition Fabienne 2010
Michel Steiger
Cristina Cavallari, Barbara Luppi,
Pharmaceutical preparations for
EP2019666 A2 EP20070734379 Pietra Anna Maria di and Lorenzo 2009
transdermal use
Rodirguez
Topical and transdermal delivery
Doron Friedman, Joeph Schwartz
US 6004566 A US 08/036, 116 system utilizing submicron oil 2007
and Haim Aviv
spheres
Ancerewicz Jacek, Kienzler Jean-
WO2002017905 A2 PCT/EP2001/010041 Treatment of burns Luc, SallinDominique and Schumann 2002
Phyllis
Cristina Cavallari, Barbara Luppi,
Pharmaceutical preparations for
2007129162 PCT/IB2007/001061 Pietra Anna Maria Di and Lorenzo 1999
transdermal use
Rodirguez
Topical and transdermal delivery
Doron Friedman, Joseph Schwartz
US 6113921 A US 09/006, 446 system utilizing submicron oil 1993
and Haim Aviv
spheres

TABLE 3: VARIOUS MARKETED EMULGEL FORMULATIONS WITH THEIR MANUFACTURERS

Voltren emulgel Diclofenac diethyl ammonium Novartis Pharma

Miconaz-H-emulgel Miconazole nitrate and hydrocortisone Medical Union Pharmaceuticals

Diclomax emulgel Diclofenac sodium Torrent Pharma

Kleraderm Gaia 480 emulgel Bidens pilosa extract Kleraderm Pharma

Isofen emulgel Ibuprofen Beit Jala Pharmaceuticals

Cataflam emulgel Diclofenac diethyl ammonium Novartis Alcon

September-October 2022 Indian Journal of Pharmaceutical Sciences 1113

 www.ijpsonline.com
The main problem in front of the formulation scientist Acknowledgement:
is the development of a new formulation for the
delivery of hydrophobic drugs due to their poor water We are greatly thankful to our Head of Institute and
solubility which ultimately affects the bioavailability Institute Management for supporting this research
of drugs. 40 % of the drugs are hydrophobic and their project.
delivery to the biological system has been challenging. Conflict of interests:
Therefore, topical drug administration is one of the
significant approaches to conquer the shortcomings The authors declared no conflict of interests.
associated with oral administration including solubility
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