Pharmaceutical Development and Technology

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Formulation and Evaluation of Curcumin Gel for

Topical Application

Nikunjana A. Patel, Natvar J. Patel & Rakesh P. Patel

To cite this article: Nikunjana A. Patel, Natvar J. Patel & Rakesh P. Patel (2009) Formulation and
Evaluation of Curcumin Gel for Topical Application, Pharmaceutical Development and Technology,
14:1, 83-92, DOI: 10.1080/10837450802409438

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 Pharmaceutical Development and Technology, 14:83–92, 2009
Copyright © Informa UK, Ltd.
ISSN: 1083-7450 print / 1097-9867 online
DOI: 10.1080/10837450802409438
LPDT
Formulation and Evaluation of Curcumin Gel for Topical Application
Nikunjana A. Patel, Natvar J. Patel, and Rakesh P. Patel
Topical Gel Delivery Systems for Curcumin
S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Mehsana, Gujarat, India
The aim of the present investigation was to develop and
study topical gel delivery of curcumin for its anti-inflammatory
effects. Carbopol 934P (CRB) and hydroxypropylcellulose
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(HPC) were used for the preparation of gels. The penetration
enhancing effect of menthol (0–12.5% w/w) on the percutaneous
flux of curcumin through the excised rat epidermis from 2% w/w
CRB and HPC gel system was investigated. All the prepared gel
formulations were evaluated for various properties such as com-
patibility, drug content, viscosity, in vitro skin permeation, and
anti-inflammatory effect. The drug and polymers compatibility
was confirmed by Differential scanning calorimetry and infrared
spectroscopy. The percutaneous flux and enhancement ratio of
curcumin across rat epidermis was enhanced markedly by the
addition of menthol to both types of gel formulations. Both types
of developed topical gel formulations were free of skin irritation.
In anti-inflammatory studies done by carrageenan induced rat
paw oedema method in wistar albino rats, anti-inflammatory
effect of CRB, HPC and standard gel formulations were signifi-
cantly different from control group (P < 0.05) whereas this effect
was not significantly different for CRB and HPC gels formulations
to that of standard (diclofenac gel) formulation (P > 0.05). CRB gel
showed better % inhibition of inflammation as compared to
HPC gel.
Keywords curcumin, carbopol 934, HPC, topical gGel, in vitro
permeation study, anti-inflamatory
INTRODUCTION
NSAIDs have been widely used in the treatment of
rheumatoid arthritis and other related conditions. However,
they carry the risk of undesirable systemic side effects and
Received 8 June 2008, Accepted 31 July 2008.
Address correspondence to Nikunjana A. Patel, Lecturer,
Department of Pharmacognosy, S. K. Patel College of Pharmaceutical
Education and Research, Ganpat University, Kherva 382711,
Mehsana, Gujarat, India; E-mail: shailyrakesh@yahoo.com
83
gastrointestinal irritation at the usual dose of oral adminis-
tration.[1] Topical and transdermal products are important
classes of drug delivery systems, and their use in therapy is
becoming more widespread. The purpose of topical dosage
forms is to conveniently deliver drugs to a localized area
of the skin.[2]
Curcumin (CUR), a constituent of Curcuma longa
(Family-Zingiberaceae), chemically known as diferuloyl-
methane has been reported to possess anti-oxidative,[3]
anti-inflammatory,[4] anticarcinogenic,[5] and hypocholes-
terolemic properties.[6] Some of the novel formulations
developed using curcumin include liposomes,[7] solid lipid
nanoparticles,[8] transdermal film,[9] microspheres,[10]
nanoemulsion,[11] etc. Following oral administration (up to
8 g per day),[12] it is poorly absorbed,[13] and only the traces of
compound appear in blood. It undergoes extensive first-pass
metabolism,[14] and hence is a suitable candidate for topi-
cal gel formulation.
Considering the fact that most inflammatory diseases
occur locally and near the surface of the body, topical
application of CUR on the inflamed site can offer the
advantage of delivering a drug directly to the disease site
and producing its local effect.[15,16] However, the barrier
properties of intact skin limit the permeability of wide
variety of substances, including pharmaceutical active
agents.[17] The most promising technique to reduce barrier
properties of stratum corneum is the use of chemical
enhancers that allow drug permeation through the skin at an
appropriate rate for a suitable time. The chemical enhancers
that have been studied are azone and its analogs, pyrroli-
dones, polyunsaturated fatty acids, alkanols, polymeric
enhancers, nonionic surfactants, and terpenes.[18–22]
An ideal penetration enhancer should be pharmacologi-
cally inactive, nonirritant, nondamaging for the skin, potent,
and cosmetically acceptable.[23] Terpenes, the naturally
occurring volatile oils, posses most acceptable criteria as
penetration enhancers like high percutaneous enhancement
ability, reversible effect on the lipids of stratum corneum,
minimal percutaneous irritancy at low concentrations (1–5%)
and good evidence of freedom from toxicity.[24–27]
 84 N.A. Patel et al.

Menthol, a monocyclic monoterpene free from toxic
effects, has been approved as a penetration enhancer in the
transdermal delivery of several drugs.[28] It enhanced the
transdermal transport of several hydrophilic and lipophilic
drugs.[29,30] Menthol, used in the present study, is l-menthol
that occurs most widely in nature.
Carbopol (CRB) and Hydroxypropylcellulose (HPC)
are widely used in the pharmaceutical and cosmetic indus-
tries to give viscous or gel formulations. Carbomers are
made of polymers of acrylic acid crosslinked with allyl
sucrose or with allyl pentaerythritol, and the degree of
cross-linking determines their viscosity.[31] Both these
polymers posses several desirable attributes as gelling
agent like high viscosity at low concentrations, quite stable
to heat with negligible batch-to-batch variability, increase
the stability of the formulations and also give them a
pleasant texture, unaffected by aging, do not support bacte-
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934P and menthol were generous gift from Lincoln
Pharmaceuticals Ltd (Ahmedabad, India). HPC was
procured from Colorcon Asia Pvt Ltd (Mumbai, India).
Other materials used in the study (methanol, potassium
dihydrogen phosphate, etc.) were of analytical grade.
Double-distilled water was used throughout the study.
Investigation of Physicochemical Compatibility
of Drug and Polymer
The physicochemical compatibility between CUR and
polymers used in the gel formulations was studied by
using differential scanning calorimetry (DSC- Shimadzu
60 with TDA trend line software, Shimadzu Co., Kyoto,
Japan) and fourier transform infrared (FTIR-8300, Shimadzu
Co., Kyoto, Japan) spectroscopy.

rial or fungal growth, and are nonirritating.[32–34]
The aim of the present study was to evaluate the suit-
ability of the transdermal route of drug delivery for CUR.
The specific goals of the research were to: (i) develop
topical gel preparations using polymer like CRB 934 and
HPC with and without permeation enhancer (menthol); (ii)
perform physicochemical characterization and in vitro
permeation studies through rat skin; (iii) to investigate the
usefulness of menthol as a penetration enhancer on the
transdermal permeability of CUR such that the required
flux of the drug could be provided from the CRB and HPC
gel reservoirs; and (iv) compare the anti-inflammatory
activity of prepared CUR topical gels with standard gel
formulation of diclofenac sodium.
In DSC analysis, the samples were hermetically
sealed in flat-bottom aluminum pans, and heated over a
temperature range of 35–300°C at a constant increasing rate
of 10°C/min in an atmosphere of nitrogen (50 mL/min). The
thermograms obtained for CUR, polymers, and physical
mixtures of CUR with polymers were compared.
The infrared (IR) spectra were recorded using an
FTIR by the KBr pellet method and spectra were recorded
in the wavelength region between 4000 and 400 cm−1. The
spectra obtained for CUR, polymers, and physical mixtures
of CUR with polymers were compared.
Preparation of Gel Formulations

The composition of different gel formulations is

MATERIALS AND METHODS shown in Table 1.

The following materials were used from the indicated CRB 934P Gels
sources without further purification procedures. CUR
powder (purity: 65–70%) was received as a gift samples Weighed quantity of CRB 934P (for ease in discus-
from Sigma Aldrich company, St Louis, MO, USA. CRB sion CRB 934P is considered as CRB throughout the

Table 1
Composition of topical gel formulations of CUR (% w/w)

Code

Materials C C1 C2 C3 C4 C5 H H1 H2 H3 H4 H5

CUR 2 2 2 2 2 2 2 2 2 2 2 2
CRB 2 2 2 2 2 2 – – – – – –
HPC – – – – – – 2 2 2 2 2 2
Triethanolamine 1 1 1 1 1 1 – – – – – –
Menthol – 2.5 5 7.5 10 12.5 – 2.5 5 7.5 10 12.5
Ethanol (96%) 30 30 30 30 30 30 30 30 30 30 30 30
Distilled water q.s. to make 100 100 100 100 100 100 100 100 100 100 100 100
 Topical Gel Delivery Systems for Curcumin
remaining text) was taken and added to the distilled water.
CUR was solubilized in an appropriate amount of ethanol
and this ethanolic dispersion of CUR was transferred to aque-
sous dispersion of CRB. The mixture was stirred gradually
by means of a stirrer (M/s. Remi otors, Mumbai, India) and
CRB was allowed to soak for 2 h. Triethanolamine was
added to neutralize the CRB solution and to form the gel.
The pH was adjusted 6.8.
HPC Gels
The HPC powder was added to required quantity of
distilled water while being stirred by means of a stirrer.
Ethanolic solution of CUR was added to the aqueous
dispersion of HPC and the resulting mixture was stirred
continuously at 37°C until the gel was formed (2 h). The gel
formulations were left overnight at ambient temperature.
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Formulations of CRB and HPC gels containing menthol
as permeation enhancer were also prepared by same meth-
ods. Menthol was incorporated in the gel formulation by
solubilizing in ethanolic dispersion of CUR.
Drug Content Studies
Drug content of the gel formulations was determined
by dissolving an accurately weighed quantity of gel (about
100 mg) in about 50 mL of pH 7.2 phosphate buffer
containing 20% v/v ethanol. These solutions were quanti-
tatively transferred to volumetric flasks and appropriate
dilutions were made with the same buffer solution. The
resulting solutions were then filtered through 0.45 μm
membrane filters before subjecting the solutions to spec-
trophotometric analysis for CUR at λmax of 425 nm. Drug
content was calculated from the linear regression equation
obtained from the calibration data.[35–37]
Viscosity Measurements
A Brookfield Rotational Digital Viscometer DV II
RVTDV-II was used to measure the viscosity (in cps) of
the gels. The spindle was rotated at 10 rpm. Samples of
the gels were allowed to settle over 30 min at the assay
temperature (25 ± 1°C) before the measurements were taken.
In Vitro Skin Permeation Studies
In vitro skin permeation studies were performed by
using a Franz diffusion cell with a receptor compartment
capacity of 21 mL and effective diffusion area of 1.84 cm2.
The excised rat abdominal skin was mounted between the
85
donor and receptor compartment of the diffusion cell. One
gram of each gel formulations was placed over the skin
and covered with paraffin film. The receptor compartment
of the diffusion cell was filled with phosphate buffer pH
7.2 containing 20% v/v ethanol. The whole assembly was
fixed on a magnetic stirrer, and the solution in the receptor
compartment was constantly and continuously stirred
using magnetic beads at 50 rpm; the temperature was
maintained at 37 ± 0.5°C. The samples were withdrawn at
different time intervals and analyzed for drug content
spectrophotometrically at a wavelength of 425 nm. The
concentration of CUR in each sample was determined
from a previously calculated standard curve. The receptor
phase was replenished with an equal volume of phosphate
buffer containing 20% v/v ethanol at each sample with-
drawal. The cumulative percent amounts of drug permeated
per square centimeter of skin were plotted against time.
Skin Irritation Test
Guidelines of the institutional animal ethics committee
were followed for this experiment. The hair on the dorsal side
of Wistar albino rats was removed by clipping 1 day before
this portion of the experiment.[38] The rats were divided into
5 groups (n = 6). Group I and II served as the control (CRB
and HPC gels without drug, respectively), group III received
CRB gel (C5), group IV received HPC gel (H5), and group V
received an 0.8% v/v aqueous solution of formalin as a stan-
dard irritant.[39] The control formulations, gel formulations
and formalin solution were applied daily for seven days.
Finally, the application sites were graded according to a
visual scoring scale, always by the same investigator.
Anti-Inflammatory Studies
Anti-inflammatory studies of prepared formulations
were compared by carrageenan-induced rat paw oedema
method in Wistar albino rats. The protocol was approved
by the Institutional Animal Ethics Committee. Thirty rats
were divided into five groups of six rats each for various
treatments as shown in Table 4. Group I and II served as
control for CRB and HPC gel formulation, respectively,
group III and IV received CRB and HPC gel (containing
4 mg of CUR), respectively, and group V received
diclofenac gel (containing 2 mg of diclofenac [1% w/w])
as a standard formulation. Animals were fasted for 24 h
before the experiment with free access to water. Approxi-
mately 0.1 mL of 1% carrageenan suspension in saline
was prepared 1 h before each experiment and was injected
into the plantar side of right hind paw of rat. 200 mg of gel
containing 2% w/w of CUR were applied to the plantar
 86 N.A. Patel et al.
surface of the hind paw by gently rubbing 50 times with
the index finger. Rats of the control groups received only the
gel base. 200 mg Diclofenac gel 1.0% w/w (Diclomol®,
Win-medicare, India) applied in the same way was used as
a reference. Drugs or placebo were applied 1 h before the
carrageenan injection. The paw volume was measured ini-
tially and at 1, 2, 3 and 4 h after carrageenan injection
using plythesmographic method of Harris and Spencer.[40]
Percentage inflammation was calculated for comparison.
Data Analysis and Statistics
The permeation parameters such as flux, permeability
coefficient, and enhancement ratio were calculated for
prepared gel formulations of CRB & HPC.
The flux (μg/cm2·h) of CUR was calculated from the
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slope of the plot of the cumulative amount of drug perme-
ated per cm2 of rat epidermal membrane at steady state
against the time using linear regression analysis.[41,42]
The steady state permeability coefficient (Kp) of the
drug across rat epidermal membrane was calculated by
using the following Equation:[43]
J Both types of gel formulations were found to contain
Kp = (1)
C
where J is the flux and C is the concentration of CUR in
donor compartment.
The penetration enhancing effect of menthol was
calculated in terms of enhancement ratio (ER), and was
calculated by using the following Equation:[24]
Kp with penetration enhancer
ER = (2)
Kp without penetration enhancer
The data obtained in this study was subjected to
statistical analysis using GraphPad-Prism 3.0 Software, for a
one-way analysis of variance (ANOVA) following Student-
Newman-Keuls multiple comparisons test. P value of less
than 0.05 was considered as evidence of a significant
difference.
RESULTS AND DISCUSSION
Physicochemical Compatibility of Drug and Polymer
The DSC analysis of pure CUR showed a sharp
endothermal peak at 178.02°C, corresponding to its melt-
ing point. The DSC analysis of the physical mixture of the
CUR and the polymers revealed a negligible change in the
melting point of CUR in the presence of the polymer mix-
tures studied (173.39°C for the CRB gel and 170.23°C for
HPC gel).
The IR spectral analysis of CUR alone showed that
the principal peaks were observed at wavenumbers 3509,
1683, 1512, 1283, and 927 cm−1, confirming the purity of
the drug. In the IR spectra of the physical mixture of CUR,
CRB, Triethanolamine and menthol the major peaks of
CUR were observed at wavenumbers 3497, 1678, 1503,
1287, and 931 cm−1; for the physical mixture of CUR,
HPC, and menthol, they were observed at 3502, 1687,
1517, and 938 cm−1. However, some additional peaks
were observed with the physical mixture, possibly because
of the presence of polymers and other formulation excipi-
ents. The DSC and IR results suggest that the drug and
polymers are compatible. Wade and Weller reported that
HPMC, HPC, PVP, and other common polymers are pop-
ular in controlled- and sustained release matrix-type films
because of their compatibility with several drugs.[44]
Drug Content and Viscosity
99.2–100.1% of CUR. As the concentration of menthol
increased in the formulations the viscosity was decreased
in both gel formulations (Table 2).
In Vitro Skin Permeation Studies
The penetration enhancing effect of menthol on the
permeability of CUR across the excised rat epidermis from
CRB and HPC gel system was investigated. Permeation
parameters for CUR from the gel formulations are shown
in Table 2. The cumulative amount of drug permeated
through rat epidermis from both type of gel formulations
containing various amounts of menthol is shown in Figure 1a
and 1b.
The maximum amount (Q24) of CUR that permeated
during the 24 h of the study was 1212.08 ± 32.44 μg cm−2
and 1081.46 ± 28.39 μg cm−2 from CRB and HPC gels
prepared without menthol, respectively. The flux was
obtained by dividing the cumulative amount of drug
permeated per cm2 of the skin with time. Thus, the
corresponding flux of CUR was 46.85 ± 1.76 μg cm−2 h−1
and 42.03 ± 1.51 μg cm−2 h−1 for the CRB and HPC gels
without menthol.
A marked effect of menthol on CUR permeation was
observed when it was incorporated in both types of gel for-
mulations in varying quantities. The cumulative amounts
(Q24) of CUR that permeated over 24 h were found to have
 Downloaded by [University of Florida] at 21:12 06 August 2017

Table 2
Drug content, viscosity, amount of drug permeated in 24 h (Q24), % CUR released, flux (J), permeability coefficient (Kp), Enhancement Ratio (ER), and zero order R2 values for
the in vitro permeation study across rat epidermal membrane from CRB and HPC gel formulations of CUR containing selected concentrations of menthol at the end of 24 h

Formulation Viscosity % CUR R2

code Drug contenta η(cps×103)a Q24a (μg cm−2) releaseda J (μg cm−2 hr−1)a Kp (cm hr−1 ×103)a ERa (Zero-order)b

C 99.2 ± 3.5 84 ± 2.37 1212.08 ± 32.44 11.15 ± 0.18 46.85 ± 1.76 2.36 ± 0.07 1.00 0.9956
C1 99.8 ± 2.4 82 ± 2.24 2293.12 ± 58.01 21.10 ± 0.24 93.36 ± 2.21 4.68 ± 0.09 1.98 ± 0.04* 0.9901
C2 99.7 ± 2.1 80 ± 2.28 4739.06 ± 96.57 43.60 ± 0.47 187.93 ± 3.39 9.48 ± 0.13 4.02 ± 0.07* 0.9871
C3 99.4 ± 1.9 78 ± 2.08 7205.33 ± 174.21 66.29 ± 0.95 280.37 ± 3.92 14.10 ± 0.18 5.97 ± 0.09* 0.9842
C4 100.0 ± 2.1 77 ± 2.01 9227.27 ± 234.73 84.89 ± 1.66 362.91 ± 4.76 18.13 ± 0.23 7.68 ± 0.13* 0.9831
C5 100.1 ± 2.3 75 ± 2.06 9645.62 ± 279.91 88.73 ± 1.82 368.40 ± 5.22 18.40 ± 0.31 7.79 ± 0.17*,# 0.9825
H 99.4 ± 3.7 117 ± 2.49 1081.46 ± 28.39 9.95 ± 0.12 42.03 ± 1.51 2.11 ± 0.08 1.00 0.9829
H1 99.6 ± 3.1 111 ± 2.33 1912.82 ± 51.73 17.59 ± 0.38 76.13 ± 1.97 3.82 ± 0.13 1.81 ± 0.05* 0.9953
H2 99.7 ± 2.7 108 ± 2.28 3351.07 ± 79.43 30.83 ± 0.74 131.30 ± 2.77 6.59 ± 0.17 3.11 ± 0.08* 0.9989
H3 100.1 ± 2.8 104 ± 2.17 5300.67 ± 122.44 48.76 ± 1.01 204.86 ± 3.83 10.23 ± 0.19 4.84 ± 0.09* 0.9886
H4 100.0 ± 2.5 101 ± 2.05 6329.88 ± 169.50 58.23 ± 1.49 243.36 ± 4.42 12.18 ± 0.23 5.76 ± 0.12* 0.9848
H5 99.9 ± 2.4 97 ± 1.99 7640.29 ± 200.33 70.29 ± 1.64 294.16 ± 4.90 14.69 ± 0.26 6.95 ± 0.14* 0.9774
a
Mean ± SD, n = 3.
b
Zero-order R2 from 2 to 24 h.
*Significant at P < 0.05 when compared with control (formulation C).
#
Insignificant at P > 0.05 when compared with control (formulation H).
 88 N.A. Patel et al.

(a)
12000

10000

Cummulative amount of drug permited 8000

(µg/cm2)

6000

4000

2000
Downloaded by [University of Florida] at 21:12 06 August 2017

0
0 5 10 15 20 25
Time (hr)
C C1 C2 C3 C4 C5
(b)
9000

8000
Cummulative amount of drug permited

7000

6000
(µg/cm2)

5000

4000

3000

2000

1000

0
0 5 10 15 20 25
Time (hr)

H H1 H2 H3 H4 H5

Figure 1. (a) Mean (± SD) amount of CUR permeated from CRB gel containing various concentrations of menthol through excised
rat epidermis (n = 3); (b) Mean (± SD) amount of CUR permeated from HPC gel containing various concentrations of menthol
through excised rat epidermis (n = 3).

increased ranging from 2293.12 ± 58.01 to 9645.62 ±
279.91 μg cm−2 for CRB gel and 1912.82 ± 51.73
to 7640.29 ± 200.33 μg cm−2 for HPC gel containing
2.5–12.5% w/w of menthol. The corresponding flux values
were ranging from 93.36 ± 2.21 to 368.40 ± 5.22 μg cm−2 hr −1
and 76.13 ± 1.97 to 294.16 ± 4.90 μg cm−2 hr −1 for CRB and
HPC gels, respectively. However, lag period of 1 h was
observed in both types of gel formulations in the perme-
ation of the drug through stratum corneum. It may be
observed from the results (Figure 1a and 1b) that there was
a constant flux of the drug up to 5% of menthol and rapid
increase in the flux of the drug with 7.5% and more of
menthol in both types of gel formulations. When the data
were analyzed for zero order, first order and higuchi
 Topical Gel Delivery Systems for Curcumin
kinetic, the amount of drug permeated best fitted to zero
order kinetics as compared to first order and higuchi
kinetic right from 2–24 h with a lag period of about 1 h for
both type of gel formulations (zero order r2 values ranges
from 0.9825–0.9956 for CRB gel and 0.9774–0.9989 for
HPC gel formulations) (Table 2).
As menthol concentration increased from 0–12.5% w/w,
the permeability of CUR was found increased (Figure 2) as
indicated by an increase in both the permeability coeffi-
cient and ER (Table 2). There was an eight-fold and
seven-fold increase in the permeability of the drug observed
from the CRB and HPC gel containing 12.5% w/w of
menthol, respectively. In case of CRB gel formulations, on
increasing the menthol concentration further from 10–12.5%
w/w, the increase in the permeability was insignificant
(P > 0.05). Both the permeability coefficient (Kp) and ER
of CUR were found unaltered from the CRB gel
Downloaded by [University of Florida] at 21:12 06 August 2017
containing more than 10%w/w of menthol whereas in
case of HPC gels Kp and ER increased linearly with all
menthol concentrations (Table 2). The CRB gels con-
taining higher amounts of menthol (10 and 12.5%)
showed a fine layer of precipitated menthol during the
permeability studies might be because of the saturation
solubility of menthol in ethanol-water.[42,45] It was
reported that terpenes increase the drug percutaneous
permeation mainly by disrupting the intercellular
packing of the SC lipids.[24,46,47]
Formulation C5 and H5 showed highest in vitro per-
meability of CUR and hence they were selected for skin
irritancy and anti-inflammatory studies
12000
Cummulative amount of drug permited
10000
8000
(µg/cm2)
6000
4000
* *
2000
*
0
0 2
Figure 2. Effect of menthol concentration on the permeation of CUR from CRB and HPC gel (n = 3) through rat epidermis.
*significant at P < 0.05 when compared to control; **insignificant at P > 0.05 when compared to 10% w/w menthol.
89
Skin Irritation Test
The skin irritation test of the CRB (C5) and HPC (H5)
gel formulations showed a skin irritation score (erythema
and edema) of less than 2 (Table 3). According to Draize
et al., compounds producing scores of 2 or less are consid-
ered negative (no skin irritation).[48] Hence, the both types of
developed topical gel formulations are free of skin irritation.
Anti-Inflammatory Studies
The results of anti-inflammatory activity after topical
application of gel formulations are reported in Table 4. In
both control formulations, the paw volume linearly increases
with time. CRB, HPC and standard gel formulations showed
better reduction in paw volume measurement as compared to
control formulations. Statistical analysis showed that the
edema inhibition of CRB, HPC and standard gel formulations
were significantly different from control group (P < 0.05).
The results also showed that the anti-inflammatory effect of
CRB and HPC gels formulations (containing 4 mg of CUR)
was similar to the effect of standard gel formulation
(diclofenac gel containing 2 mg of diclofenac) (P > 0.05).
CONCLUSIONS
Topical route of application has a great potential as an
effective and safe way to administer curcumin for local
**
*
*
*
* *
*
4 6 8 10 12 14
Concentration of menthol (% w/w)
CRB gel HPC gel
 90 N.A. Patel et al.

Table 3
Skin irritation scores following topical CUR gels application

Control (CRB gel) Control (HPC gel) C5 H5 Formalin

a b a b a b a b
Rat No Erythema Edema Erythema Edema Erythema Edema Erythema Edema Erythemaa Edemab

1 0 0 0 0 1 1 1 1 3 2
2 0 0 0 0 1 0 2 1 3 2
3 0 0 0 0 0 1 1 0 3 3
4 0 0 0 0 2 1 0 1 3 1
5 0 0 0 0 1 1 1 0 3 3
6 0 0 0 0 0 1 1 1 2 2
Average 0.83 ± 0.31c 0.83 ± 0.17c 1.00 ± 0.26c 0.66 ± 0.21c 2.83 ± 0.17 2.17 ± 0.40
a
Erythema scale: 0, none; 1, slight; 2, well defined; 3, moderate; and 4, scar formation.
b
Edema scale: 0, none; 1, slight; 2, well defined; 3, moderate; and 4, severe.
c
Significant compared with formalin (P < 0.05).
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Table 4
Anti-inflammatory activity of different topical gel formulations of CUR

Paw volume (ml)a at time after carrageenan injection

Treatment No. Initial 1h 2h 3h 4h

Control (CRB gel) 6 1.71 ± 0.11 2.90 ± 0.22 3.08 ± 0.24 3.12 ± 0.33 3.15 ± 0.37
C5b 6 1.70 ± 0.13 2.01 ± 0.19 [73.95] 2.11 ± 0.20 [70.07] 2.22 ± 0.25 [63.12] 2.27 ± 0.27 [60.42]
Diclofenac gel 6 1.71 ± 0.14 1.99 ± 0.20 [76.47] 2.10 ± 0.23 [71.53] 2.19 ± 0.28 [65.96] 2.26 ± 0.32 [61.81]
Control (HPC gel) 6 1.69 ± 0.12 2.74 ± 0.25 2.86 ± 0.29 2.99 ± 0.31 3.03 ± 0.34
H5b 6 1.65 ± 0.13 1.96 ± 0.21 [70.48] 2.07 ± 0.24 [64.10] 2.15 ± 0.26 [61.54] 2.19 ± 0.28 [59.70]
Diclofenac gel 6 1.71 ± 0.14 1.99 ± 0.20 [73.33] 2.10 ± 0.23 [66.67] 2.19 ± 0.28 [63.08] 2.26 ± 0.32 [58.96]
a
Values are mean ± SEM [percent reduction].
b
ANOVA analysis showed that both formulations (C5 and H5) were significantly different from control group (P < 0.05) and not
significantly different from standard formulation (diclofenac gel) (P > 0.05).

anti-inflamatory effect. In vitro permeation study across
rat epidermal membrane and anti-inflammatroy studies by
carrageenan induced rat paw oedema method showed that
menthol enhanced the transdermal absorption of curcumin
from carbopol and hydroxypropylcellulose gel drug reser-
voir system. The topical gel formulations of curcumin
developed in this study have great utility and are a viable
option for effective and controlled management of inflam-
mation. Further experiments are to be conducted in other
animal models for anti-inflammatory effect. Based on the
results of these tests, trials may be performed on humans.
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