Drug Delivery

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

Formulation and evaluation of novel controlled

release of topical pluronic lecithin organogel of
mefenamic acid

Vikas Jhawat, Sumeet Gupta & Vipin Saini

To cite this article: Vikas Jhawat, Sumeet Gupta & Vipin Saini (2016) Formulation and evaluation
of novel controlled release of topical pluronic lecithin organogel of mefenamic acid, Drug Delivery,
23:9, 3573-3581, DOI: 10.1080/10717544.2016.1212439

To link to this article: https://doi.org/10.1080/10717544.2016.1212439

Published online: 05 Aug 2016.

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Drug Deliv, 2016; 23(9): 3573–3581

! 2016 Informa UK Limited, trading as Taylor & Francis Group. DOI: 10.1080/10717544.2016.1212439

RESEARCH ARTICLE

Formulation and evaluation of novel controlled release of topical

pluronic lecithin organogel of mefenamic acid
Vikas Jhawat, Sumeet Gupta, and Vipin Saini

Department of Pharmacology, M. M. College of Pharmacy, M. M. University, Mullana, Ambala, Haryana, India

Abstract Keywords
In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical In vitro anti-inflammatory activity, in vitro
carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by release, mefenamic acid, pluronic lecithin
a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in organogels
varying concentrations to study various parameters using in vitro diffusion study and in vivo
studies. All formulations were found to be off-white, homogenous, and reluctant to be washed History
easily and have pH value within the range of 5.56–5.80 which is nonirritant. Polymer
concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted Received 9 May 2016
in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of Revised 6 July 2016
gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were Accepted 10 July 2016
found to be more stable and retard the drug release from the gel. The formulations of F2 and
F3 were selected for kinetic studies and stability studies, as they found to have all physical
parameters within acceptable limits, highest percent drug content and exhibited highest drug
release in eight hours. The order of drug release from various formulations was found to be
F24F34F104F44F14F94F84F54F74F6. The optimized formulation F2 was found to
follow zero order rate kinetics showing controlled release of the drug from the formulations.
In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a
standard marketed preparation (Volini gel) was found satisfactory and significant.

Introduction avoid drug degradation in stomach due to internal body

conditions and various metabolizing enzymes, first pass
Mefenamic acid is a drug of NSAIDs category having anti-
effect, irritation of GI mucosa, ease of application, controlled
inflammatory and analgesic activity. It is used in management
rate drug release, constant drug blood level, patient compli-
of pain and inflammation, swelling and uterine contractions
ance and decreased side effects with minimum discomfort
by inhibition of prostaglandin synthesis. Conventional oral
(Kumar et al., 2010). But, it is not easy to deliver a drug
dosage form of mefenamic acid is available in the form of
through skin such as stratum corneum; the outermost and
capsules but like other NSAIDs, mefenamic acid is also prone
toughest layer of the skin is the major barrier which is
to cause gastrointestinal ulceration, rashes and intestinal
composed of corneocytes containing dead keratin
bleeding when administered by oral route. The aqueous
(Arunachalam et al., 2010). To enhance the permeation of
solubility of mefenamic acid is very low (20 mg/l) and major
drug through the skin and to increase the bioavailability of the
metabolism occurs in liver and excretion by kidney, which
drug, various approaches have been utilized such as applica-
further reduces its oral bioavailability. Therefore an attempt is
tion of permeation enhancers, novel drug delivery systems
made to deliver mefenamic acid through skin for better
such as vesicular systems (Schmid & Korting, 1994),
bioavailability along with local action and to avoid gastric
nanoparticles, microspheres (Abrol et al., 2004) and poly-
side effects. It is 90% protein bound drug with apparent
meric lipid gels. Pluronic lecithin based organogels (PLO
volume of distribution 1.06 l/kg having half-life of two hours.
gels) have the potential to permeate through skin and deliver
Log p value of mefenamic acid is 4.1 and molecular weight is
sufficient quantity of drug for local as well as systemic action.
241.285 g/mol, which makes it a suitable candidate for
Therefore, we have chosen PLO gels for the topical delivery
transdermal route. Therefore, transdermal administration of
of mefenamic acid, which is expected to deliver the drug
mefenamic acid will be promising, as transdermal route has
across the skin for better results. PLO gels are nonirritant and
many advantages over other conventional oral routes such as
biocompatible composed of phospholipid (lecithin) as sur-
factant, an organic solvent as outer continuous phase and an
Address for correspondence: Sumeet Gupta, Professor, Department of aqueous polar phase/solvent. The entangled reverse micelles
Pharmacology, M. M. College of Pharmacy, M. M. University, Mullana,
Ambala, Haryana, India. Tel: +91 9872620252, +918059930156. forms a 3D network which entraps the outer continuous
E-mail: sumeetgupta25@gmail.com nonpolar phase and immobilizes it turning into a viscous gel
3574 V. Jhawat et al. Drug Deliv, 2016; 23(9): 3573–3581

by self-association of individual gelator molecules
(Scartazzini & Luisi, 1988; Schurtenberger et al., 1990).
Several categories of drugs such as NSAIDS, hormones,
opiods, local anesthetics and anti-emetic drugs have success-
fully been incorporated in PLO gels (Dumortier, 2006).
Both hydrophilic and lipophilic types of drugs having
molecular weight less than 400 Da can be easily incorporated
into PLO gel formulation. The composition of PLO gel
includes oil phase containing phospholipid lecithin as
permeation enhancer, isopropyl myristate (IPM)/palmitate as
a solvent for lecithin and emollient for skin having a good
spreading rate and sorbic acid as preservative and aqueous
phase containing pluronic F-127 as surfactant, purified water
as solvent and potassium sorbate as preservative (Kumar &
Katare, 2005; Vintiloiu & Leroux, 2007; Belgamwar, 2009).
Various studies show that PLO gel formulations are much
better than oral tablets in the treatment of inflammation. So,
the present study was undertaken to develop PLO gel
formulation of mefenamic acid for anti-inflammatory activity
using in vivo method in rat model.
Materials and methods
Materials
ensure complete dissolution of lecithin and sorbic acid
in IPM.
Aqueous phase: Aqueous phase was prepared by dissolving
weighed quantity of pluronic F-127 and potassium sorbate
and menthol in cold water. The mixture was kept below 4  C
in refrigerator for 12 h for complete dissolution of pluronic
F-127.
Next day, gel was prepared by adding slowly oil phase to
aqueous phase at a high shear using mechanical stirrer so that
a uniformly dispersed microemulsion is formed. Drug was
incorporated in oil phase by making a paste with polyethylene
glycol 400 before mixing with pluronic phase (Garg et al.,
2011). Menthol was added as soothing agent and permeation
enhancer.
Visual characters of organogel system
The knowledge of molecular packing and formation of cross
linking bridges within the organogel network and entrapment
of aqueous phase in the lipid polymer phase was observed
using light microscope and scanning electron microscope
(Kasliwal et al., 2008).
Organoleptic characteristics

Mefenamic acid was obtained as a gift sample from K Pharma
(Ambala, India). Pluronic F-127 was purchased from Sigma
Aldrich (Delhi, India), Soya lecithin and disodium hydrogen
phosphate were purchased from Himedia laboratories Pvt.
Ltd. (Mumbai, India), IPM, sorbic acid potassium sorbate,
potassium dihydrogen orthophosphate, and sodium chloride
and sodium hydroxide were purchased from Qualikems Fine
Chem. Pvt. Ltd. (New Delhi, India). Menthol was purchased
from Avon Flavors (Mumbai, India). All other chemicals were
also of analytical grade.
Methods
Preparation of organogel
PLO gel is a microemulsion prepared by mixing of aqueous
and oil phase at a high shear. Ten formulations of PLO gel
(Table 1) with varying concentrations of lecithin and pluronic
F-127 were prepared by the below method comprising of the
two phases, i.e. oil phase and aqueous phase (Umamaheswari
et al., 2002; Belgamwar, 2009).
Oil phase: The oil phase is prepared by taking a measured
amount of lecithin and sorbic acid in IPM as a solvent.
The above mixture was kept at room temperature for 12 h to
Each formulation was tested for various organoleptic charac-
teristics such as odor, color, texture, phase separation and
greasiness (Kasliwal et al., 2008).
Homogeneity test
Gel (100 mg) was pressed between the thumb and the index
finger in order to notice the consistency of gel that any coarse
particles being attached or detached on finger (Agrawal et al.,
2010).
Washability
PLO gel (100 mg) was rubbed on backside skin of the hand.
After drying the layer was washed with tap water and
observed whether it is washable or not (Agrawal et al., 2010).
pH determination
The pH of all the gel formulations was determined using
digital pH meter which was calibrated before measurements
using standard buffer solutions of pH 7 and pH 4. After
calibration, the electrode was dipped in an aqueous solution of
gel (1 g in 20 ml water) at 25  C which directly gives the pH of
the gel formulation (Murthy & Kishore, 2008; Singh, 2009).

Table 1. Formulation of PLO gels from F1 to F10.

Formulations
Types of phase Ingredients (% w/w) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Oil phase Mefenamic acid 1 1 1 1 1 1 1 1 1 1
Lecithin 2 4 6 8 10 4 4 4 4 4
Sorbic acid 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
100 100 100 100 100 100 100 100 100 100
Aqueous phase Pluronic F 127 20 20 20 20 20 5 10 15 25 30
Potassium sorbate 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2
Menthol 3 3 3 3 3 3 3 3 3 3
Distilled water (up to) 100 100 100 100 100 100 100 100 100 100
DOI: 10.1080/10717544.2016.1212439 Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel
Viscosity (rheological characters)
Viscosity (in terms of centipoises: cps) of all the formulations
was determined using Brookfield digital viscometer (DV-I
Prime, Brookfield Engineering Laboratory, Inc., Middleboro,
MA). Tests were performed at 25  C and temperature was
controlled using a water bath. Viscosity was determined using
the spindle (LV 61) rotating at 10 rpm (Singh, 2009).
Spreadability
Spreadability of each formulation was determined by an
apparatus defined by Mutimer et al. (1956) containing two
glass slides. Gel (1 g) was placed between the slides and a
weight of 1000 g was placed on upper slide to allow the gel to
spread uniformly. Now weights were added to the weight pan
and the time traveled by the movable slide for a particular
distance was noted and spreadability of different gels was
calculated by the below formula (Mutimer et al., 1956):
S ¼ M  L=T
where S is the spreadability of gel in g cm/s, M is the weight
placed in the weight pan, L is the distance traveled by the
movable slide in cm, and T is the total time taken by the slide
to travel the distance L (Kumar & Katare, 2005).
Gel transition temperature
The gel transition temperature was determined in a 20 ml
transparent vial that contains a magnetic bead. Each formu-
lation (10 g) was placed in a water bath maintained at 4  C and
temperature was increased gradually at a rate 1  C/min while
stirring the magnetic bead at 60 rpm. The temperature at
which the magnetic bead stopped moving was noted as
gelation temperature of gels (Baloglu et al., 2011).
Drug content
Drug content of different formulations was calculated using
UV spectrophotometer. Gel (100 mg) was dissolved in 100 ml
buffer and filtered through 0.45 mm syringe filter. After
filtration the drug content was found out by taking absorbance
at lmax 285 nm (Nemutlu, 2005).
In vitro diffusion study
In vitro diffusion study was performed to calculate the percent
cumulative drug release with respect to time. Franz diffusion
cell having two compartments, i.e. upper donor compartment
and lower receiver compartment separated by a semi perme-
able cellophane membrane was used. PLO gel (1 g) was
placed in donor compartment and receiver compartment
was filled with phosphate buffer pH 7.4. Whole assembly was
maintained at 37  C with constant stirring. Samples were
taken at time intervals of 0, 1, 2, 3, 4, 5, 6, 7 and 8 h. One
milliliter sample was withdrawn and an equal quantity of
phosphate buffer pH 7.4 was replaced after each sampling.
Samples were analyzed after making proper dilutions using
UV spectrophotometer at lmax 285 nm to determine the
percent cumulative drug release (Nemutlu, 2005).
3575
Stability study
The stability testing of PLO gel formulations was carried out
in humidity chamber (I-Therm Inc.) according to the ICH
guidelines. The chamber was operated at 4  C, 25  C/65% of
relative humidity and 60  C/75% of relative humidity for three
months and evaluated for percent drug content, pH and
physical stability to check phase separation (Agrawal et al.,
2010).
Animals
Albino rats (Wistar strain) of either male or female of about
200–250 g were used after obtaining the approval of the
Institute Animal Ethics Committee (MMCP/IAEC/12/25).
The animals were housed under standard conditions of
temperature (24 ± 28  C) and relative humidity (60–70%)
with a 12:12 light–dark cycle. The animals were fed a
standard pellet diet (Lipton India, Ltd., Kolkata, India) and
water ad libitum.
Skin irritation study
Skin irritation study was performed in each group of six rats.
The hairs were removed from the back of the rat with the help
of hair removing cream. An area of 4 cm2 was marked on both
the sides. After 24 h of depilation, the formulations were
applied (100 mg/rat) once a day for seven days and sight was
covered with cotton bandage (Kulkarni & Jain, 2001). The rat
was observed for sign and symptoms of any sensitivity and
reaction that may occur and were classified as: 0 No reaction,
0.5 Slight, patchy erythema, 1 Slight but confluent or
moderate but patchy erythema, 2 Moderate erythema and 3
Severe erythema with or without edema.
Experimental design for in vivo studies (analgesic and
inflammation activity)
Rats were divided into three different groups (six rats each)
and treated as follows. Group 1: Normal treated control group,
Group 2: Positive control group, Group 3: Standard marketed
formulation treated group (Volini gel; 100 mg), Group 4: Test
formulation treated group (PLO gel; 100 mg).
Eddy’s hot plate method
In this method, heat was the source of pain to check the
analgesic activity of drug. Individually animals were placed
on Eddy’s hot plate (Techno Instrument India) maintained at
constant temperature of 55 ± 1  C. Time taken by animal for
any of the reaction either paw licking or jumping or raising
the limbs, which ever will be observed first will be taken as
end point. Reaction time was noted before and 30 min after
administration of the drug (Rohit et al., 2006).
Carrageenan induced rat paw edema model
The drug was applied 30 min before carrageenan administra-
tion. Each 0.1 ml of 1% w/v carrageenan was injected into the
rat paw of all the groups except normal control group after
30 min of the drug administration. The paw edema volume
was measured with digital plethysmometer (Model 7140,
UGO Basile, Monvalle, Italy) after a gap of 0 h, 1 h, 2 h, 3 h
3576 V. Jhawat et al.
Figure 1. Carrageenan induced paw edema test.
and 4 h (Figure 1). The percentage inhibition of edema
compared with that of the control was taken as anti-
inflammatory activity. The percentage inhibition of edema
was calculated by the formula:
Percentage inhibition of edema ¼ (AB)/A  100 where A
represents the paw volume of the control group and B
represents the paw volume of the test drug treated group
(Crunkhorn & Mencock, 1971).
Statistical analysis
The data were expressed as mean ± standard error of mean
(SEM). The statistical significance between mean was
analyzed using one-way analysis of variance (ANOVA)
followed by Tukey’s multiple comparison test. A p value of
50.05 was considered as statistically significant.
Results
Ten formulations were prepared with varying concentrations
of lecithin (F1–F5) and pluronic F 127 (F6–F10) and
evaluated for various formulation parameters.
Organoleptic characteristics
The gel formulations were observed for physical appearance
and other organoleptic characteristics. All formulations were
Drug Deliv, 2016; 23(9): 3573–3581
found homogenous, odorless, off-white in color, greasy and
reluctant to wash and stable without any sign of phase
separation.
Surface morphology of organogel
Light microscopic examination of organogel (F2) at 10  40
resolutions has shown organogel as bi-continuous systems
containing water molecules entrapped within the self-
assembled three-dimensional network of the gelator
(Figure 2).
SEM photographs of the gel (F2) at 10  1000 resolutions
clearly showed the gel forming the highly viscous three-
dimensional network structure. The three-dimensional net-
worked structure, so formed, prevents the flow of external
apolar phase (Figure 2).
pH
The pH of all PLO gel formulations were found in the range
5.57–5.80 which is in the normal range of skin pH. Therefore
all PLO gel formulations are nonirritant to the skin (Table 2).
Spreadability
The values of spreadability indicate that the gel is easily
spreadable with small shear but increase in percentage of
DOI: 10.1080/10717544.2016.1212439 Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel 3577

Figure 2. Light microscope structure at 10  40 resolution (1) and SEM image at 10  1000 resolution of organogel formulation (F2).

Table 2. Evaluation parameters of organogel formulations (F1–F10).

S. no. Formulation pH Spreadability (g.cm/s) Viscosity (in cps) Skin irritation study Gel transition temperature
1. F1 5.60 ± 0.67 30.18 ± 2.82 2738 ± 4.82 No irritation 35.4  C ± 0.99
2. F2 5.58 ± 0.27 21.92 ± 1.37 2872 ± 8.34 No irritation 33.2  C ± 1.02
3. F3 5.61 ± 0.59 17.94 ± 0.773 2936 ± 10.95 No irritation 32.8  C ± 0.88
4. F4 5.59 ± 1.81 13.48 ± 0.213 2989 ± 1.93 No irritation 30.3  C ± 1.01
5. F5 5.58 ± 0.93 10.42 ± 0.392 3052 ± 27.82 No irritation 29.1  C ± 0.72
6. F6 5.56 ± 0.62 40.50 ± 2.811 2542 ± 15.84 No irritation 33.9  C ± 1.11
7. F7 5.61 ± 0.46 27.02 ± 2.080 2681 ± 11.23 No irritation 32.1  C ± 0.94
8. F8 5.57 ± 0.23 21.62 ± 0.560 2767 ± 9.39 No irritation 31.7  C ± 0.61
9. F9 5.80 ± 0.19 14.27 ± 0.236 2995 ± 24.15 No irritation 31.2  C ± 0.58
10. F10 5.75 ± 0.14 8.26 ± 0.346 3176 ± 11.98 No irritation 29.8  C ± 1.09

lecithin resulted in decrease in the spreadability of

organogels from F1 to F5 (30.18–10.42 g.cm/s). Likewise
same trend was observed when percentage of pluronic
was increased in formulations from F6 to F10 (40.50–
8.26 g.cm/s) (Table 2). This decrease in spreadability of
gels with increase in polymer concentration is because of
increase in the cross linking between polymers which resist
it to spread easily.

Viscosity
The viscosity of gel formulations was found in the range from
2738 cps to 3052 cps (F1–F5) and from 2542 cps to 3176 cps
(F6–F10). The proportional increase in the viscosity with
polymer concentration can be attributed to the incidence of
more cross linking in polymer with increase in polymer
concentration, as viscosity curve given in Figure 3. PLO gels
show shear thinning, non-Newtonian behavior with pseudo Figure 3. Viscosity values of formulations from F1 to F10.
plastic flow (Table 2).

Skin irritation study

Absence of skin irritation in gel formulation is acceptable.
There was no erythema, edema or reddening of skin. All gel
formulations found were free from any sign of irritation
(Table 2).
Gel transition temperature
The gel transition temperature of 10 organogel formulations
were evaluated between the range of 35.4  C and 29.1  C (F1–
F5) and 33.9–29.8  C (F6–F10). As the polymer concentration
3578 V. Jhawat et al. Drug Deliv, 2016; 23(9): 3573–3581

increases the gel strength also increases and the gelation concentration showed less variation in drug release profile.
occurred at lower temperature (Table 2). Since the number and dimension of aqueous region available
for diffusion of the drug are reduced with the possible
Percentage drug content increase in microviscosity in the three-dimensional structure
of the gel. Figure 4 shows percentage cumulative drug release
The percentage drug content of organogels was found in the profile from F1 to F5 and from F6 to F10.
range from 96.25% to 98.36%. It was calculated by using the Based on above studies, we found that formulations F2 and
standard curve of MA in PBS 7.4 (Table 3). F3 are suitable for further kinetic data fitting stability study,
as these have shown all physical parameters within acceptable
Percent cumulative drug release limits and showed the highest percent cumulative drug release
in eight hours. Therefore F2 and F3 formulations were further
Formulations with higher percentage of lecithin retarded the
tested for different rate equations. F2 formulation was found
drug release and have higher viscosity. The percent cumula-
to follow zero order rate kinetics (Table 5) with r2 value 0.996
tive drug release in eight hours was found in the order
when compared to F3 which indicates it as a controlled
F24F34F104F44F14F94F84F54F74F6 (Table 4).
release formulation.
It may be noted that increase in lecithin concentration
showed retardation in release of MA in F1–F5 formulations
Stability study
but in F6–F10 formulations, the increase in pluronic
Formulations F2 and F3 were found to be sufficiently stable
during study period at all temperature ranges. Pluronic gels
Table 3. Percentage drug content of organogels. were in semisolid to liquid state at temperature 60  C
depending on polymer concentration but no phase separation
S. no. Formulations Percentage drug content occurs up to 60 days in F2 formulation and up to 30 days in F3
1. F1 97.18 ± 0.314 formulation. However on prolonged study at 60  C PLO gels
2. F2 96.25 ± 0.310 started showing phase separation (Table 6). Therefore finally
3. F3 98.29 ± 1.440
4. F4 97.16 ± 0.236 F2 formulation was then selected for in vivo anti-inflamma-
5. F5 96.73 ± 0.205 tory activity.
6. F6 95.92 ± 0.201
7. F7 97.21 ± 0.310 In vivo study
8. F8 96.79 ± 0.115
9. F9 98.36 ± 0.115 Hot plate method
10. F10 98.09 ± 0.831
The analgesic effect of PLO gel of mefenamic acid was
compared with control group and standard group (Volini gel).
Table 4. Percentage cumulative drug release in 8 h .
Normal reaction time in control group animals was 4–8 s.
S. no. Formulations Percent cumulative drug release
Reaction time was significantly increased in test group
animals but it was almost within the range of standard
1. F1 74.8 group, i.e. 10–13 s. The statistical analysis also showed non-
2. F2 88.4
3. F3 85.7
4. F4 78.2
5. F5 67.4 Table 5. Kinetic data of release studies for F2 and F3 formulations.
6. F6 58.6
7. F7 63.8 Zero order First order Higuchi Hixson Crowell
8. F8 67.6 Formulation
2 2 2
9. F9 72.7 code r K0 r K1 r KH r2 KHC
10. F10 78.8
F2 0.996 11.32 0.887 0.114 0.968 43.49 0.920 0.276
Bold values which signified the best two formulations for further study. F3 0.987 10.98 0.863 0.887 0.946 41.91 0.944 0.299

Figure 4. Percentage cumulative drug release

profile of F1–F5 and F6–F10 formulations.
DOI: 10.1080/10717544.2016.1212439 Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel 3579
Table 6. Stability study data of F2 and F3 formulations.

% drug content pH Phase separation


Time (days) Temp ( C) F2 F3 F2 F3 F2 F3
0 4 95.98 ± 0.24 98.29 ± 0.02 5.58 ± 0.32 5.61 ± 0.34 No separation No separation
15 4 95.69 ± 0.49 98.01 ± 0.22 5.53 ± 0.33 5.59 ± 0.32 No separation No separation
30 4 95.48 ± 0.13 97.74 ± 0.31 5.61 ± 0.24 5.42 ± 0.21 No separation No separation
60 4 95.22 ± 1.21 97.41 ± 0.28 5.54 ± 0.41 5.53 ± 0.33 No separation No separation
90 4 94.67 ± 0.42 97.11 ± 0.35 5.49 ± 0.37 5.49 ± 0.15 No separation No separation
15 25 95.51 ± 0.32 97.87 ± 0.32 5.51 ± 0.24 5.58 ± 0.33 No separation No separation
30 25 95.19 ± 0.43 97.32 ± 1.23 5.43 ± 0.15 5.93±.37 No separation No separation
60 25 94.47 ± 0.62 96.63 ± 0.95 6.23 ± 0.33 6.21 ± 0.34 No separation No separation
90 25 93.98 ± 0.15 96.19 ± 0.54 5.69 ± 0.37 6.10 ± 0.41 No separation No separation
15 60 95.13 ± 0.32 97.45 ± 0.65 5.83 ± 0.54 5.79 ± 0.23 No separation No separation
30 60 94.52 ± 1.51 96.82 ± 1.75 6.11 ± 0.41 6.27 ± 0.46 No separation No separation
60 60 93.29 ± 0.96 96.12 ± 1.42 5.97 ± 0.57 6.13 ± 0.58 No separation Slight separation
90 60 92.65 ± 1.63 95.54 ± 1.76 5.71 ± 0.59 5.91 ± 0.61 Slight separation Slight separation

of the present study was to formulate and evaluate different

Figure 5. Analgesic activity of mefenamic acid organogel formulation
using Eddy’s hot plate.
significant effect when compared between standard and test
formulation (F2), which also confirmed that both the formu-
lation showed same type of effect (Figure 5).
Carrageenan induced paw edema
The results (Figure 6) showed that both the formulations (F2
and marketed) produced statistically significant inhibition
(p50.0001) of edema when compared with positive control
group after second hour onwards but at third and fourth hour,
our F2 formulation showed non-significant effect when
compared with marketed formulation indicating similar type
of inhibitory activity. Test formulation was found to be
28.55% and 33% and marketed formulation was produced
30.16% and 35.52% at third and fourth hour (Table 7).
Discussion
Searching of new drug molecule and development of
pharmaceutical product is a tedious method in the laboratory
now days. On the other side, marketed products are well
known for its therapeutic activity and with serious adverse
effects. Best drug delivery system is our target for the drug to
achieve its goal without any serious side effects. The objective
organogel tropical formulations of mefenamic acid with
varying concentrations of pluronic and lecithin. In our
study, all gel formulations were found to have all physical
parameters within acceptable limits such as homogenous, off-
white in color, odorless, greasy and stable without any sign of
phase separation. The organogel formulations were somewhat
reluctant to wash. The pH of our organogel formulations was
found to be near skin pH range and showed good compati-
bility with skin. Polymer concentration is one of the
parameter to measure the viscosity, spreadability and percent
cumulative drug release. Our study showed that, when the
polymer concentration increases then the viscosity was also
elevated and it is directly proportional to the polymer
concentration. Therefore increase in lecithin concentration
(F1–F5) or pluronic concentration (F6–F10) increases the
viscosity of gel formulations and reduces the spreadability
due to increase in resistance between layers. Thus, the percent
cumulative amount of drug release was reduced, as the
viscosity of the formulations increased and these results were
in accordance with earlier study findings (Pandey et al.,
2010). The gelation temperature range of our formulations
lies below normal body temperature because our formulation
exists in gel state and similar findings were also reported by
Ba et al. (2016). The skin irritation study was also performed
on rats and all formulations showed no detectable sign of skin
irritation, indicating excellent compatibility with skin. Based
on different evaluation parameters (Table 2), the optimized
formulations F2 and F3 were selected for further rate kinetics
study and stability study. In stability study, data of F2 and F3
formulations for three months are within range in accordance
with the ICH guidelines and same result was found in the
literature reported by Pandey et al. (2010). Our F2 and F3
formulations showed no sign of phase separation during
storage and no significant macroscopic changes in physical
parameters, percentage drug content and pH. In the rate
kinetic data, formulation F2 follows zero order release kinetic
as compared to F3 which will deliver the drug at controlled
rate, therefore, F2 formulation was then selected for in vivo
analgesic and anti-inflammatory activity. In vivo analgesic
activity studies on animals (Figures 5 and 6 and Table 7)
indicated that, our F2 formulation and marketed diclofenac
gel (Volini gel) formulation showed similar type of activity
3580 V. Jhawat et al. Drug Deliv, 2016; 23(9): 3573–3581

Figure 6. Anti-inflammatory mefenamic acid

organogel using digital plethysmograph.

Table 7. Mean values of paw volume at different time intervals.

Time (h) Normal control Positive control Standard (marketed formulation) Test (F2) Overall p value F value
0 0.835 ± 0.019 0.839 ± 0.018 0.823 ± 0.014 0.843 ± 0.021 0.284 1.356
1 0.862 ± 0.021 0.961 ± 0.065 0.902 ± 0.059ns (6.13%) 0.913 ± 0.062ns (4.9%) 0.0407 3.320
2 0.840 ± 0.019 1.036 ± 0.076 0.797 ± 0.015d,a (23%) 0.899 ± 0.035d,a,e,b (13.22%) 50.0001 34.28
3 0.832 ± 0.017 1.096 ± 0.075 0.760 ± 0.017d,a (30.16%) 0.783 ± 0.013d,a,e,ns (28.55%) 50.0001 90.60
4 0.831 ± 0.013 1.14 ± 0.075 0.735 ± 0.018d,a (35.52%) 0.741 ± 0.014d,a,e,ns (33%) 50.0001 138.12

Statistical analysis of data was carried by one-way ANOVA followed by Tukey’s Multiple Range Test. The values are Mean ± SD for each group (n ¼ 6)
and the experiments were repeated thrice.
a
p50.0001.
b
p50.01.
c
p50.05.
d
Positive control versus formulation.
e
Test formulation group versus standard group.
ns: nonsignificant.

indicating non-significant effect when compared with each
other, whereas in inflammation induced rat model, at 2 h, test
formulation showed slightly significant effect (p50.01) when
compared with marketed formulation but at third hour and
fourth hour, F2 formulation showed non-significant effect
when compared with marketed formulation which indicated
that, our F2 formulation is having same therapeutic activity
than that of marketed formulations (Volini gel). Although, the
effectiveness of F2 formulation and marketed gel formulation
was almost same for analgesic and anti-inflammatory
activities but our formulation (Topical organogel) could be
better effective alternative to diclofenac marketed gel as
diclofenac gel have short duration and low intensity activity.
Being organic in nature and presence of lecithin (a component
of skin phospholipids) these have a very high potential to
permeate the drug through the skin so these can easily deliver
the drug across the skin. Therefore, more studies are needed
to optimize the organogel formulations to get the superior
results.
Conclusion
Therefore, from the above study we conclude that organogels
are novel base for drugs through topical route and could be an
alternative to the marketed diclofenac gel formulations.
Our F2 formulation may come as a new drug in the market
for the treatment of inflammation after following various
phases of clinical trials and ethical guidelines.
Acknowledgements
The authors are grateful to the management for offering the
requisite technical help to accomplish this study.
Declaration of interest
The authors declare that there is no conflict of interest
regarding the publication of this paper.
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