Drug Delivery

ISSN: 1071-7544 (Print) 1521-0464 (Online) Journal homepage: https://www.tandfonline.com/loi/idrd20

Formulation development, in vitro and in vivo

evaluation of microemulsion-based gel loaded
with ketoprofen

Kishor V. Nikumbh, Shailesh G. Sevankar & Moreshwar P. Patil

To cite this article: Kishor V. Nikumbh, Shailesh G. Sevankar & Moreshwar P. Patil (2015)
Formulation development, in�vitro and in�vivo evaluation of microemulsion-based gel loaded with
ketoprofen, Drug Delivery, 22:4, 509-515, DOI: 10.3109/10717544.2013.859186

To link to this article: https://doi.org/10.3109/10717544.2013.859186

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ISSN: 1071-7544 (print), 1521-0464 (electronic)

Drug Deliv, 2015; 22(4): 509–515

! 2013 Informa Healthcare USA, Inc. DOI: 10.3109/10717544.2013.859186

ORIGINAL ARTICLE

Formulation development, in vitro and in vivo evaluation of

microemulsion-based gel loaded with ketoprofen
Kishor V. Nikumbh, Shailesh G. Sevankar, and Moreshwar P. Patil

Department of Pharmaceutics, MET’s Institute of Pharmacy, Bhujbal Knowledge City, Adgaon, Nashik, India

Abstract Keywords
Background: Anti-inflammatory agents are widely used to relieve inflammation caused by Anti-inflammatory activity, emulgel, ex vivo
various factors. release, globule size, zeta potential
Aim: This study was initiated with the intention to deliver low aqueous soluble ketoprofen to
enhance its solubility by developing microemulsion system as a template and then History
incorporating it into gel phase.
Materials and methods: Initially ketoprofen was solubilized into microemulsion preparation Received 5 September 2013
made up of clove oil, Tween 20 and propylene glycol as oil phase, surfactant and co-surfactant Revised 22 October 2013
respectively, then it was incorporated into different concentration of gelling phase using Accepted 22 October 2013
gelling agents namely Carbopol 940, Carbopol 934 and hydroxypropyl methyl cellulose K4M
(HPMC K4M). Formulated emulgels were evaluated for their physical appearance, pH,
rheological properties, globule size, extrudability, drug content, spreadability, bioadhesion
strength, in vitro and ex vivo drug release, skin irritation test and anti-inflammatory activity.
Results: Microemulsion had shown globule size 396 nm, pH 6–6.7, viscosity 29.4 cps and zeta
potential 12 mV indicating good stability. Formulated emulgels showed good physical
appearance, skin acceptable pH 6–6.9, non-Newtonian shear thinning system, drug content
99.28  0.16%, bioadhesion strength 48.4 gram force, globule size 473 nm, spreadability
22.96 gm.cm/s, good extrudability, in vitro release, ex vivo release did not showed any irritation
reaction and possess a good anti-inflammatory activity.
Conclusions: Selected batch showed enhanced drug release (92.42  4.66%) as compared to
marketed gel (65.94  3.30). Similarly ex vivo release of formulation showed 72.22% release
through mice skin compared with marketed gel. Formulations followed Korsmeyer–Peppas
diffusion kinetic model. It was observed from the results that the formulated emulgel can
provide promising delivery of ketoprofen.

Introduction anti-inflammatory action is due to inhibitory effect on

cyclooxygenase-2, an enzyme involved in prostaglandin
Inflammation is an important nonspecific local protective
synthesis that is responsible for inflammation.
reaction to the tissue injury, caused by pathogens or wound.
Emulgels are emulsions or microemulsions, either of the
Acute inflammation is the immediate response of the body to
water-in-oil type or oil-in-water type, which are gelled by
injury or cell death (Willey et al., 2008). In last few decades,
using suitable gelling agents. Emulsified gel is stable and
research demonstrated that inflammation is regulated by
better vehicle for delivery of hydrophobic or poorly water
many pro and anti-inflammatory chemical mediators like
soluble drugs. They have a high patient compliance since they
histamine, prostaglandins (PEG2 and prostacyclins),
possess the advantages of both emulsions and gels. Direct
leukotrien B4, serotonin, bradykinin, cytokines (interleukin
(oil-in-water) systems are used to entrap lipophilic drugs,
[IL]-1, IL-6, IL-11 and tumor necrosis factor-a), reactive
whereas hydrophilic drugs are entrapped in the reverse
oxygen species, growth factors and lysosomal enzymes of
(water-in-oil) system (Jain et al., 2010; Joshi et al., 2011;
neutrophils (Khatib et al., 2010). Inflammation is the result of
Singla et al., 2012).
concerted participation of a large number of vasoactive,
Emulgels for dermatological use have several favorable
chemoactive and proliferative factors at different stages
properties such as being thixotropic, greaseless, easily
(Tripathi, 2003). Ketoprofen is chemically a propionic acid
spreadable, easily removable, emollient, long shelf life, bio-
derivative, non steroidal anti-inflammatory drug (NSAID). Its
friendly, transparent and pleasing appearance (Magdy, 2004).
Microemulsion is defined as a dispersion consisting of oil,
Address for correspondence: Kishor V. Nikumbh, Department of surfactant, cosurfactants and aqueous phase, which is a single
Pharmaceutics, MET’s Institute of Pharmacy, Bhujbal Knowledge City,
Adgaon, Nashik 422 003, Maharashtra, India. Tel: +919850630624.
optically isotropic and thermodynamically stable liquid solu-
Email: sgsmax1@gmail.com tion usually within the range of 10–100 nm. Microemulsions
510 K. V. Nikumbh et al.
have several advantages such as enhanced drug solubility,
good thermodynamic stability, ease of manufacturing and
enhancement effect on transdermal ability over conventional
formulations. Recently, increasing attention has focused on
microemulsions for transdermal delivery of hydrophobic drugs
(Chen et al., 2004; Hyun et al., 2012; Sahle et al., 2012).
Carbopols are high molecular weight polymers of acrylic
acid cross-linked with allyl ethers of pentaerythritol. The
molecular weight of carbopol resins is theoretically estimated
at 7  105 to 4  109. Carbopol disperse in water to form
acidic colloidal solutions of low viscosity, these solutions
when neutralized produce highly viscous gel (Bugay &
Findlay, 1999; Rowe et al., 2009).
Ketoprofen possesses poor water solubility and high
hydrophobicity (Gordon et al., 2006), it also causes gastric
irritation when taken orally, hence creates limitation in
formulating as oral dosage forms (Renceber et al., 2009).
This study was aimed to develop and evaluate emulgel
formulation containing ketoprofen, as the market survey
indicated the absence of ketoprofen emulgel to be applied
directly on the affected area with the objective of releasing
drug locally and more effectively. The study was initiated using
microemulsion as a template consisting of clove oil as oil
phase, Tween 20 as surfactant and propylene glycol as a
cosurfactant, which helps in solubilization of hydrophobic
ketoprofen in its fine globule droplets, it was then incorporated
into separately prepared gel phase using Carbopol 940,
Carbopol 934 and HPMC K4M to get homogeneous and
thickened emulgel; this could result in low concentration of
drug in emulgel as compared to gel. To achieve these
objectives, the emulgel was evaluated for the influence of
pH, rheological properties, bioadhesion strength, spreadability,
in vitro drug release, globule size, ex vivo release, zeta
potential, extrudability and drug content. The anti-inflamma-
tory activity of selected ketoprofen containing formulation
using carrageenan-induced paw edema had been evaluated and
compared with commercial gel formulation (Fastum gelÕ ).
Materials and methods
Materials
Ketoprofen was kindly gifted by Cipla Ltd., (Daman, India).
Carbopol 940 was purchased from Loba chemicals (Mumbai,
India). Carbopol 934 was supplied from Research Lab
Fine Chemicals (Mumbai, India). HPMC K4M was purchased
from Dow chemicals (Mumbai, India). Tween 20, clove
oil, triethanolamine (TEA), methylparaben, propylparaben,
sodium hydroxide, potassium dihydrogen phosphate and
methanol were supplied from Thomas Baker (Mumbai,
India). All the chemicals used during study were of analytical
reagent grade and used further without dilutions. Albino mice
were obtained from Haffkine Institute (Mumbai, India).
Solubility studies
Screening of oils, surfactants and cosurfactants for
microemulsion
To find out suitable oil, surfactant and cosurfactants phase in
microemulsion, the solubility of ketoprofen was screened in
various oils, almond oil, clove oil, liquid paraffin, oleic acid
Drug Deliv, 2015; 22(4): 509–515
surfactants, Tween 20, Tween 80 and cosurfactants like
Capmul MCM L8, propylene glycol and Captex. An excess
amount of ketoprofen was added to 3 ml of selected oils,
surfactants and cosurfactants separately in 10 ml capacity
stopper vials. Then the mixture was vortexed using a
cyclomixer (Remi motor, Mumbai, India) for 10 min in
order to facilitate proper mixing of drug with the vehicles
and then stirred for 48 h at 40  0.5  C. Furthermore, the
mixtures were kept for 24 h at room temperature to reach
equilibrium. The equilibrated samples were centrifuged at
3000 rpm for 15 min followed by filtration through a 0.45 mm
membrane filter. The filtrates were diluted with methanol
subsequently quantified by ultraviolet (UV)-spectrophoto-
meter at 260 nm.
Pseudo ternary phase diagrams
Ketoprofen showed maximum solubility in clove oil as
compared to other oils; hence, it was selected for further
studies. Tween 20, as a surfactant, and propylene glycol, as
cosurfactants, showed better solubility for ketoprofen and
good emulsifying properties with clove oil. Pseudo ternary
phase diagrams were constructed using water titration
method. Surfactant and cosurfactant (Smix) were mixed in
different weight ratios (1:1, 1:2, 1:3, 2:1 and 3:1). Oil and
Smix mixture were mixed thoroughly in different weight ratios
(1:9, 2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2 and 9:1). Distilled water
was added drop wise to the different mixtures of oil/Smix until
cloudy dispersion was obtained. Pseudo ternary plots were
constructed using Chemix School Software, trial version 3.6
(Oslo, Norway), and microemulsions were prepared based on
ternary phase diagram.
Formulation of microemulsion
From all five-phase diagrams, the ratio of 2:1 S/Cos concen-
tration showed higher self microemulsifying region
(Figure 1), hence selected for formulation of microemulsion.
Right part from boundary line in phase diagram shows us
the region in which self microemulsifying region exists.
Figure 1. Pseudo ternary phase diagram of microemulsion (2:1).
DOI: 10.3109/10717544.2013.859186 Microemulsion-based ketoprofen gel 511

A larger microemulsion region is responsible for the higher pH determination

microemulsifying potential of the combination. Thus, it is
helpful in finding regions having better ability at lower
proportion of cosurfactants and having higher drug loading
potential.
Preparation of emulgel
For the preparation of emulgel, initially microemulsion was
prepared. The oil phase was prepared by dissolving methyl
and propylparabens in propylene glycol and it was added into
clove oil. Ketoprofen was added into oil phase. Aqueous
phase was prepared by incorporating Tween 20 into distilled
water, and then both the phases were mixed using constant
stirring to get transparent microemulsion. For the preparation
of gelling phase, Carbopol 940 and Carbopol 934 were
dispersed in distilled water with continuous stirring to get
homogeneous dispersion, while HPMC K4M was separately
dispersed in hot distilled water (75  C) and the stirred
continuously until room temperature was reached. The pH
was adjusted in between 6 and 6.5 using TEA. The gelling
phase was slowly mixed with microemulsion in 1:1 ratio with
constant and uniform stirring to get milky white homoge-
neous emulgel. The composition of different formulations is
given in Table 1.
Evaluation of microemulsion
Measurement of globule size and zeta potential
The globule size and zeta potential were measured using
Zetasizer Nano – ZS (Malvern instruments, Worcestershire,
UK). The measurement was performed at 25  C. A sample,
1 ml, was diluted using double distilled water (Yang et al.,
2006; Graf et al., 2009).
The pH of all formulations was determined by using
calibrated pH meter MK VI (Systronic, Mumbai, India). A
dispersion, 10%, was made up with distilled water and
measurements were carried out at ambient temperature
(Bhanu et al., 2011).
Rheological study
Viscosity was determined at 37  1  C using Brookfield
digital viscometer-LV DV E (Brookfield, Massachusetts,
USA) with spindle 96 at different rpm (Mostafa et al., 2011).
Spreadability
Spreadability was determined by apparatus suggested by
Mutimer. Apparatus consist of a wooden block, which was
attached to a pulley at one end. Spreadability was measured on
the basis of ‘‘Slip and Drag’’ characteristics of emulgel.
A ground glass slide (7.5  2.5 cm) was fixed on the wooden
box. Emulgel formulation under the study, 1 gm, was placed on
this ground slide. The formulation was then sandwiched
between ground slide and upper glass slide having same
dimensions as that of ground slide and it was provided with the
hook. Weight of 50 gm was allowed to rest on upper slide for
2 min to expel air and to provide uniform film of formulation.
Known weight was placed in the pan attached to the pulley with
the help of hook. The time required to cover distance of 7.5 cm
was recorded. A shorter interval indicates better spreadability
(Joshi et al., 2012). It is calculated using the formula:
S ¼ M  L=T
where M is the weight tied to upper slide, L is length of glass
slide and T is time taken to separate the slide.

Phase separation Globule size measurement

Microemulsions were subjected to centrifugations at
10 000 rpm for a period of 30 min and observed for any
phase separation (Patravale & Bachhav, 2009).
Evaluation of prepared emulgel
Physical appearance
The prepared ketoprofen emulgel formulations were inspected
visually for their color, homogeneity and consistency (Thakur
et al., 2012).
Globule size of emulgel formulations was determined by
using Zetasizer Nano – ZS (Malvern instruments). Sample
preparations were made by dissolving 1 gm of formulation in
double distilled water (Khunt et al., 2012).
Drug content determination
Ketoprofen content in emulgel was measured by dissolving
known quantity of jellified emulsion in solvent (methanol) by
sonication. Absorbance was measured after suitable dilution

Table 1. Composition of emulgel formulations.

Component (% w/w) EG 1 EG 2 EG 3 EG 4 EG 5 EG 6 EG 7 EG 8
Ketoprofen 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
Carbopol 940 1.5 2.0 – – 1.0 1.0 – –
Carbopol 934 – – 1.5 2.0 – – 1.0 1.0
HPMC K4M – – – – 0.5 1.0 0.5 1.0
Clove oil 10 10 10 10 10 10 10 10
Tween 20 27 27 27 27 27 27 27 27
Propylene glycol 13 13 13 13 13 13 13 13
Methylparaben 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03
Propylparaben 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01
Triethanolamine q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
Water q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.
512 K. V. Nikumbh et al.
at 255 nm in UV-spectrophotometer and % drug content was
calculated.
In vitro drug release
This study was carried out using the modified diffusion
cell. Samples, each 1 gm of the different formulations, were
spread on egg membrane previously soaked overnight in the
diffusion medium. The loaded membrane was firmly
stretched over the edge of glass tube of 3.10 cm diameter.
The tube was then immersed in the receptor medium, which
contained 200 ml of the diffusion medium (phosphate buffer,
pH 7.4) previously warmed and maintained at 37  1  C and
stirred at 100 rpm using magnetic stirrer. Aliquots of 10 ml
were withdrawn from the receptor medium at different time
intervals. Withdrawn samples were replaced by equal volume
of fresh medium. The samples were analyzed at 260 nm
against blank using UV-spectrophotometer. Experiments were
carried out in triplicates.
Bioadhesion study
The fresh mice skin was cut into pieces (2.5 cm2) and washed
with 0.1 N NaOH. Two pieces of mice skin were tied to the
two glass slides separately; from that, one slide was fixed on
the wooden platform and another piece was tied with the
balance on right-hand side. The right and left pans were
balanced by adding extra weight on the left-hand side. About
1 gm of emulgel was placed between these two slides
containing hairless mice skin, and extra weight from left
pan was removed to sandwich the two pieces of skin and
applied pressure to remove entrapped air. The balance was
kept in this position for 5 min, then water was added slowly to
the left hand pan until the both skins were separated. The
weight (gram force) of water required to detach emulgel from
the skin surfaces was noted as bioadhesive strength. The
bioadhesive strength is calculated using formula (Khullar
et al., 2011):

surfactant, which provides stable microemulsion due to the
Bioadhesive strength ¼ Weight requiredðin gramsÞ=Area cm2
Ex vivo diffusion study
This study was performed by using the freshly shaven mice
skin as a diffusion membrane. Skin was soaked into diffusion
medium (phosphate buffer, pH 7.4) overnight and then it was
stretched to the diffusion tube. Emulgel formulation, 1 gm
was placed on the membrane and dipped it into receptor
medium and maintained the temperature at 37  1  C,
aliquots of 10 ml were withdrawn at different time intervals,
and same volume of buffer was added to maintain sink
conditions. The release profile data of prepared emulgel
formulation was compared with the marketed gel (Fastum
gelÕ ).
Skin irritation study
A set of five mice was used in the study. The emulgel
formulation (EG 3) was applied on the properly shaven skin of
mice. Undesirable skin changes, i.e. change in color and
changes in skin morphology, were observed for a period of
24 h (Khullar et al., 2012).
Drug Deliv, 2015; 22(4): 509–515
In vivo anti-inflammatory activity
The study was conducted in accordance with the approval of
the Animal Ethical Committee, MET’S Institute of Pharmacy,
CPCSEA Reg. no-1344/ac/10/CPCSEA/IAEC. Edema was
induced on the left hind paw of the mice by subplanter
injection of 1% w/v carrageenan. Emulgel formulation EG 3
and standard (Fastum gelÕ ) were applied 30 min before
carrageenan injection. The paw volume was measured at
intervals of 30, 60, 90, 120 and 180 min by vernier caliper.
 Group 1 (control group): carrageenan (1% w/v) was
injected in the plantar surface of mice.
 Group 2 (standard group): topical marketed fastum
gel þ carrageenan (1% w/v).
 Group 3 (test group): emulgel formulation EG 3 þ car-
rageenan (1% w/v).
Each group contained five mice. The % inhibition of paw
edema in drug treated group was compared with carrageenan
control group and calculated using the formula:
%inhibition ¼ Vc  Vt =Vc  100
where Vc is the inflammatory increase in paw volume control
group and Vt the inflammatory increase in paw volume in test
group (Khullar et al., 2012).
Results and discussion
Evaluation of microemulsion
Measurement of globule size and zeta potential
The microemulsion had the less globule size as compared to
the coarse emulsion due to presence of co-surfactant, which
reduces the interfacial tension to ultra low value. Globule size
of microemulsion was found to be 396 nm (Table 2), which
did not show a conclusive pattern to correlate with formula-
tion components. The small globule size of microemulsion
was due to large percent of Smix. Similarly, zeta potential was
observed to be 12 mV due to the presence of non-ionic
neutral charge present at the diffusive boundary.
Phase separation
Emulsion is thermodynamically unstable system, which may
separate when subjected to physical stresses like centrifuga-
tion. Though microemulsions are homogeneous single phase
system, they were subjected to centrifugation to confirm the
absence of phase separation. Microemulsion did not show any
sign of phase separation when subjected to centrifugation,
which confirms physical stability of microemulsion.
Evaluation of prepared emulgels
Physical appearance
Emulgel formulations were milky white creamy preparations
with a smooth homogeneous texture and glossy appearance,
which is presented in Table 3.
Table 2. Globule size and zeta potential of microemulsion.
Formulation Globule size (nm) Zeta potential (–mV)
ME 1 396 12
DOI: 10.3109/10717544.2013.859186 Microemulsion-based ketoprofen gel 513

pH determination Globule size measurement

The pH of the topical formulations should be compatible with
skin pH. A change in the pH may cause irritation or disruption
of skin. The pH of all formulations was modified with the
help of TEA and when measured, it was found between 6 and
6.8, which is acceptable for skin preparations.
Globule size of all formulations is given in Table 4. There is
slight increase in globule size of all emulgel formulations due
to addition of gelling agent into it, as it causes entrapment of
oil globule in its network thus, responsible for slight increase
in interfacial tension between oil water phase.

Rheological study Drug content determination

Rheological behavior of the emulgel formulations exhibited
non-Newtonian shear thinning pseudo plastic type of flow, i.e.
decreases in viscosity at increasing shear rates. As the shear
stress is increased (Figure 2), the disarranged molecules of the
gelling material are caused to align their long axes in the
direction of flow. Such orientation reduces the internal
resistance of the material and decreases viscosity. An increase
in the concentration of Carbopol 940 and Carbopol 934 (1–
2%) were expected to show increase in viscosity. Emulsifier
and clove oil concentrations could be contributing to the
rheological properties of the formulations.
Spreadability
Spreadability is the term expressed to denote the extent
of area to which the gel readily spreads on application to
the skin (Figure 3). One of the essential criterias for an
emulgel is that it should have good spreadability. It depends
upon the type and concentrations of polymers used in the
formulation. More viscous formulation would have poor
spreadability. The spreadability values of all formulations
were given in Table 4. The formulation EG 3 showed more
spreading coefficient, i.e. 22.96, as compared to other
formulations, this is because formulation contained optimum
concentration of Carbopol 934, i.e. 1.5%.
The drug content of all formulations was found to be in the
range of 98–101%, which is considered as normal according
to official monograph (Indian Pharmacopoeia, 2007).
In vitro drug release
In vitro release profiles of ketoprofen from various emulgel
formulations are represented in Figure 4. Microemulsion
system contains oil globules with entrapped drug molecules
which provides enhanced solubility to drug molecule, thus,
increases the release of ketoprofen from emulgel than gel.
From the data obtained, it was observed that most of emulgel
formulations gave better release as compared to marketed gel
formulation at the end of 8 h. The higher drug release was
observed with formulations EG 3 and EG 7, i.e. 99.42% and
88.92%, respectively. The release profile up to 8 h of all
formulation is given in Table 4. The release data were analyzed
according to various kinetic models. Most of the studied
formulations followed Korsmeyer–Peppas kinetic model.
Bioadhesion study
The bioadhesion strength of emulgel formulation is given in
Table 5.

Table 3. Physical appearance of emulgel formulations.

Formulation Color Homogeneity Consistency

EG 1 Milky white Homogeneous Excellent
EG 2 Milky white Homogeneous Excellent
EG 3 Milky white Homogeneous Excellent
EG 4 Milky white Homogeneous Excellent
EG 5 Milky white Homogeneous Excellent
EG 6 Milky white Homogeneous Excellent
EG 7 Milky white Homogeneous Excellent Figure 3. Spreadability of all formulations..
EG 8 Milky white Homogeneous Excellent

Table 4. Data showing spreadability, globule size and percent drug

release.

Percent cumulative
Spreadability Globule drug release
Formulations (gm.cm/s) size (nm) (mean  SD)
EG 1 14.67 481.3 61.91  1.25
EG 2 16.07 526.5 59.48  0.85
EG 3 22.96 473 92.42  4.66
EG 4 12.05 419.1 64.43  0.14
EG 5 13.5 448.5 87.34  0.38
EG 6 17.76 494.7 67.47  0.91
EG 7 19.85 468.2 88.92  2.50
EG 8 16.07 516 77.05  2.70
Marketed gel 14.06 – 65.94  3.30
Figure 2. Rheological behavior of emulgel formulations.
514 K. V. Nikumbh et al. Drug Deliv, 2015; 22(4): 509–515

Ex vivo diffusion study The p value is 50.0001, which is considered as extremely

The ex vivo diffusion study was performed using fresh
mice skin. Study was performed using marketed gel and
formulated emulgel (EG 3) (Figure 5). The marketed gel
showed 54.44% release of ketoprofen, whereas formulated
emulgel showed 72.22% at the end of 8 h (Table 6). Both of
these figures indicated that formulated emulgel gave higher
flux and permeation as compared to standard marketed gel
preparation.
significant by applying analysis of variance (ANOVA)
followed by paired ‘‘t’’ test.
Skin irritation study
This study was performed on mice. After application of
emulgel and observed for 24 h, formulation did not indicate
any evidences of skin irritation such as redness of skin or any
change in morphology of skin. Thus, it may be concluded that
formulation does not have skin irritation potential and hence,
safe for topical application.

In vivo anti-inflammatory activity

Figure 4. In vitro release profile of all formulations.
The anti-inflammatory activity of the formulation EG 3 (test)
was compared with marketed ketoprofen gel (fastum gel) i.e.,
standard group. The % inhibitions of standard and test group
were 65.92% and 51.08%, which indicated that formulated
emulgel was more effective than marketed gel (2.5%) in its
anti-inflammatory activity even at low concentration, i.e. 2%
(Table 7). The p value is 50.0001 is considered as extremely
significant by applying ANOVA test followed by Dunnett’s
test.

Conclusion
Amongst all formulations, emulgel prepared with oil (10%),
Table 5. Bioadhesion strength.
S/Cos (40%) and Carbopol 934 (1.5%) was better with respect
Formulation Bioadhesion strength (gram force) to overall formulation qualities. Developed microemulsion
system provides solubilization of hydrophobic drug, thus
EG 3 48.4
impart availability of ketoprofen in formulation, whereas
globule size and zeta potential was 396 nm and 12 mV,
respectively, indicating the stability and proper formulation of
microemulsion. The prepared emulgel can be considered as
cost effective formulation because of reduction of topical dose
of ketoprofen in formulation. The highest release was showed

Table 6. Comparative ex vivo release profile.

Percent cumulative drug release

Time (h)
EG 3 Marketed gel
1 9.43 8.34
2 11.08 9.32
3 18.81 13.63
4 28.01 19.26
5 36.38 24.09
6 53.63 29.98
7 63.06 46
Figure 5. Comparative ex vivo release profile of formulated emulgel and 8 72.22 54.44
marketed gel.

Table 7. Percent inhibition of paw edema.

Paw volume (mm) (mean  SEM)

Group Percent inhibition
0 min 30 min 60 min 120 min 180 min
Control 2.43  0.13 4.26  0.26 4.57  0.29 4.7  0.29 4.82  0.31 0
17 48 73 71 92
Standard 2.58  0.11 4.24  0.24 3.8  0.20 3.33  0.15 3.52  0.27 65.92
86 47 07 49 76
Test 2.2  0.06 4.02  0.18 3.62  0.23 3.32  0.20 3.48  0.22 51.08
48 14 66 33 90
DOI: 10.3109/10717544.2013.859186
by EG 3 batch (92.42  4.66%), which was increased and
prolonged when compared with marketed gel. In addition,
their permeation and appearance was found to be more
acceptable. All formulations exhibited non-Newtonian
pseudo plastic behavior, i.e. it was shear thinning system.
Formulation showed no skin irritation potential as confirmed
by skin irritation study. Thus, the results of this research study
clearly indicated a promising potential of the ketoprofen
emulgel as an alternative to the conventional dosage forms.
Acknowledgements
The authors are thankful to Cipla Ltd., Daman, for generously
providing gift sample of ketoprofen. They also thank MET’s
Institute of Pharmacy, Bhujbal Knowledge City, Adgaon,
Nashik, for providing necessary facilities.
Declaration of interest
The authors report no conflicts of interest. The authors alone
are responsible for the content and writing of this article.
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