A Gupta et al.

/ Drug Invention Today 2010, 2(5),250-253

Available online through

www.ditonline.info
ISSN: 0975-7619

Research Article

Formulation and evaluation of topical gel of diclofenac sodium using different polymers
A Gupta1*, AK Mishra2, AK Singh1, V Gupta2, P Bansal 3
1

Babu Banarasi Das National Institute of Technology and Management, Lucknow, India
National Institute of Ayurvedic Pharmaceutical Research, CCRAS, Patiala, India
3
Baba Farid University of Health Sciences, Faridkot, India
2

Received on: 15-01-2010; Revised on: 15-03- 2010; Accepted on:15-04-2010

ABSTRACT
A wide choice of vehicles ranging from solids to semisolids form has been used for skin care and topical treatment of dermatological disease, High molecular
weight water soluble polymers of Hydroxypropyl methylcellulose (HPMC), Carbapol 934P, Sodium alginate that possess very high viscosity, transparency, film forming properties at low concentration, are reported to useful in formation of gel. In the present investigation Diclofenac sodium gels were
prepared for topical drug delivery by using different concentration of HPMC, Sodium alginate, Carbapol 934P, with an objective to increase transparency
and spreadability. From the study it was concluded that HPMC gel containing Diclofenac sodium showed good consistency, homogeneity, spreadability and
stability and has wider prospect for topical preparations as compared to Sodium alginate, Carbapol 934P gel containing Diclofenac sodium.

Keywords: Topical drug delivery, Diclofenac sodium, HPMC, Carbapol 934P, Sodium alginate
INTRODUCTION
For topical treatment of dermatological disease as well as
skin care, a wide variety of vehicles ranging from solids to semisolids
and liquid preparations is available to clinicians and patients. Within
the major group of semisolid preparations, the use of transparent gels
has expanded both in cosmetics and in pharmaceutical preparations
[1]. A gel is colloid that is typically 99% wt liquid, which is immobilized
by surface tension between it and a macromolecular network of fibers
built from a small amount of a gelating substance present [2]. Topical
drug administration is a localized drug delivery system anywhere in
the body through ophthalmic, rectal, vaginal and skin as topical routes.
Skin is one of the most readily accessible organs of human body for
topical administration and main route of topical drug delivery system.
Numbers of medicated products are applied to the skin or mucous
membrane that either enhance or restore a fundamental function of a
skin or pharmacologically alter an action in the underlined tissues.
Such products are referred as topical or dermatological product [3].
Hydroxypropyl methylcellulose (HPMC), Carbapol 934P, Sodium alginate has been used as hydrophilic polymers topically in gel drug
delivery system [4, 5]. A series of grades based on molecular fractions
*Corresponding author.
A Gupta
Babu Banarasi Das National Institute of Technology
and Management,
Lucknow, India
Tel.: + 91-0902346846
E-mail: abhibbd2006@gmail.com,
vikas_4308@rediffmail.com

Drug Invention Today Vol.2.Issue 5.May 2010

of these polymers are used at a concentration between 1 to 5% in

topical gel formulation. Due to their non greasy properties, they can
provide easily washable film on the skin [4, 6]. HPMC, Carbapol 934P,
Sodium alginate polymers of high molecular weight do not penetrate
the skin and are non toxic in nature [4, 7].
MATERIAL AND METHODS
Diclofenac sodium, HPMC, Carbapol 934P and Sodium alginate were procured from Babu Banarasi Das National Institute of
Technology and Management, Lucknow, India. All other ingredients
used were of analytical grade.
Procedure of gel preparation
For Formulation F1, F2, F3 1g of diclofenac sodium was
weighed and dissolved in 15ml of glycerin with the help of mild heat
(solution A). Weighed quantity of HPMC was added to the 75ml of
distilled water and stirred until dissolved (solution B). Solution A and
B were mixed thoroughly and the final weight was made up to 100g.
For Formulation F4, F5, F6 1g of diclofenac sodium was weighed and
dissolved in 15ml of glycerin with the help of mild heat (solution A).
Weighed quantity of carbapol 934P was added to the 75ml of distilled
water and stirred until dissolved and then neutralized by the 10%
NaOH (solution B). Solution A and B were mixed thoroughly and the
final weight was made upto 100g. For Formulation F7, F8, F9, 1g of
diclofenac sodium was weighed and dissolved in 15ml of glycerin
with the help of mild heat after that mixed thoroughly methyl paraben
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A Gupta et al. / Drug Invention Today 2010, 2(5),250-253

& propyl paraben (solution A). Weighed quantity of sodium alginate
was added to the 75ml of distilled water and stirred to dissolve the
same (solution B). Solution A and B were mixed thoroughly and the
final weight was made up to 100g. (Table 1)
Precipitation occurs in some of the batches (F1, F3, F4, F6,
F7 andF9) of polymer based gel containing diclofenac sodium which
could be due to the incompatibility in the system. Hence, these batches
were discarded and remaining batches (F2, F5 and F8) were considered for further study.

Viscosity
Viscosity was determined by using brookfield viscometer.
Viscosity measurements were carried out at room temperature (2527C) using a Brookfield viscometer (Model RVTDV II, Brookfield
Engineering Laboratories, Inc, Stoughton, MA). (Table 3)
Consistency
The measurement of consistency of the prepared gels was
done by dropping a cone attached to a holding rod from a fix distance
of 10cm in such way that it should fall on the centre of the glass cup
filled with the gel. The penetration by the cone was measured from
the surface of the gel to the tip of the cone inside the gel. The distance traveled by cone was noted down after 10sec. [9] (Table 3)
Homogeneity

F2

F5

F8

Figure. 1: Photo of Formulated Diclofenac Sodium Gels

All developed gels were tested for homogeneity by visual

inspection after the gels have been set in the container. They were
tested for their appearance and presence of any aggregates. (Table 3)

EVALUATION OF POLYMER BASED GEL CONTAINING Skin irritation test

DICLOFENAC SODIUM:
Test for irritation was performed on human volunteers. For
The above formulated polymer based gel containing each gel, five volunteers were selected and 1.0g of formulated gel was
Diclofenac sodium was subjected to evaluation for the following pa- applied on an area of 2 square inch to the back of hand. The volunrameters:
teers were observed for lesions or irritation. (Table 3)
Preformulation studies

Drug content

Preformulation studies are needed to ensure the development of a stable as well as therapeutically effective & safe dosage
form. It is a stage of development during which characterizes the
physico-chemical properties of the drug substance and it interaction
with various formulation components. (Table 2)

A specific quantity (100mg) of developed gel and marketed

gel were taken and dissolved in 100ml of phosphate buffer of pH 6.8.
The volumetric flask containing gel solution was shaken for 2hr on
mechanical shaker in order to get complete solubility of drug. This
solution was filtered and estimated spectrophotometrically at 276nm
using phosphate buffer (pH 6.8) as blank. [10] (Table 3)

pH
The pH of various gel formulations was determined by using digital pH meter (Table 3)

Spreadability
It was determined by wooden block and glass slide apparatus. Weights about 20g were added to the pan and the time were
noted for upper slide (movable) to separate completely from the fixed
slides. [8] (Table 3)
Spreadability was then calculated by using the formula:
S = M.L / T
Where,
S = Spreadability
M = Weight tide to upper slide
L = Length of glass slide
T = Time taken to separate the slide completely from each other
Drug Invention Today Vol.2.Issue 5.May 2010

Accelerated Stability Studies

All the selected formulations were subjected to a stability
testing for three months as per ICH norms at a temperature of 40 2.
All selected formulations were analyzed for the change in appearance, pH or drug content [11] (Table 4)
Permeability studies [12]
Phosphate buffer of pH 6.8 was used for in vitro release as
a receptor medium. The pretreated skin of albino mice was used in fraz
diffusion cell. The gel sample was applied on the skin and then fixed
in between donor and receptor compartment of diffusion cell. The
receptor compartment contained phosphate buffer (100ml) of pH 6.8.
The temperature of diffusion medium was thermostatically controlled
at 37 1 by surrounding water in jacket and the medium was stirred
by magnetic stirrer at 500rpm. The sample at predetermined intervals
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Table 1: Composition and concentration of Diclofenac sodium gel
Batch
No

Drug
(g)

F1
F2
F3
F4
F5
F6
F7
F8
F9

1
1
1
1
1
1
1
1
1

Polymer (g)
HPMC
Carbapol
(g)
934P (g)
3
3.5
4
-

0.25
0.5
0.75
-

Sodium
alginate (g)
8
8
8

10%

Glycerin

Methyl

Propyl

Distilled

NaOH

(ml)

paraben (ml)

paraben (ml)

Water (ml)

q.s.
q.s.
q.s.

15
15
15
15
15
15
15
15
15

0.1
0.2
0.3

0.05
0.1
0.15

Upto100
Upto100
Upto100
Upto100
Upto100
Upto100
Upto100
Upto100
Upto100

Table 2: Preformulation study of drug

Identification

Solubility
Methanol

Drug + 1 ml of 0.4% w/v soln.

in methanol + 1 ml. nitric
acid produced red colour

++++

Dissolution

Partition

Melting

Ethanol
(95%)

Water
& GAA

Ether,
chloroform

constant (PKa)

coefficient

point 0 C

+++

++

3.5

280

++++ Very soluble, +++ moderately soluble, ++ slightly soluble, + practically soluble

Table 3: Values of evaluation parameters of developed gel

Batch
No
F2
F5
F8

pH

Spreadability

Viscosity

Consistency Homogeneity

Skin

Drug

7.4
6.8
7.1

(g.cm/sec)
5.6
3.8
3.9

(dyns/cm 2)
0.94*10 -3
1.6*10 -3
1.7*10 -3

(60 sec)
6 mm
6 mm
5 mm

irritation
Nil
Nil
Nil

Content (%)
99.81
99.75
99.96

Very Good
Good
Good

Table 4: Stability study of various formulated gel

Serial
No
1

Batches

Months

Appearance

pH

F2

F5

F8

0
1
2
3
0
1
2
3
0
1
2
3

Clear
Clear
Clear
Clear
Clear
Clear
Clear
Clear
Clear
Clear
Clear
Clear

7.4
7.4
7.3
7.3
6.8
6.8
6.7
6.6
7.1
7.1
7.1
7.0

Drug
Content (%)
99.81
98.27
97.54
96.91
99.75
98.87
96.05
95.33
99.96
97.12
96.43
95.65

Table 5: Permeability Studies of formulated gels

Sr.
No

1
2
3
4

Time
Interval
(min)
30
60
90
120

Medium pH
Batch F2

6.8
6.8
6.8
6.8

38.54
64.78
81.23
96.87

%Drug release
Batch F5

44.61
71.35
84.38
97.72

Batch F8

56.00
75.41
90.11
98.54

were withdrawn and replaced by equal volume of fresh fluid. The

samples withdrawn were spectrophotometrically estimated at 276nm
against their respective blank. (Table 5)

chemical test, producing red colour on reaction with methanol and

nitric acid. The melting point of drug was found to be 2800C. The
solubility of drug was very soluble in methanol, soluble in ethanol,
slightly soluble in water, and practically soluble in ether. The partition
coefficient and dissolution constant were 3.5 and 4 respectively. The
pH values of all developed (F2, F5, and F8) were 7.4, 6.8 and 7.1
respectively. The values of spreadability indicate that the gel is easily
spreadable by small amount of shear. Spreadability of formulated gels
(F2, F5, and F8) were 5.6, 3.8 and 3.9 g cm/sec. Hence spreadability of
F2 formulation was good as compared to F5 and F8 formulation. The
consistency reflects the capacity of the gel, to get ejected in uniform
and desired quantity when the tube is squeezed. Hence, the consistency of F2 formulation was better as compared with F8 formulation.
All developed gel showed good homogeneity with absence of lumps.
The formulated F2 preparation was much clear and transparent as
compared to F5 and F8 formulation as shown in figure 1. The skin
irritation studies of developed gel were carried out on human volunteers and that confirmed the absence of any irritation on the applied
surface in all formulations. During the accelerated stability studies
the appearance was clear and no significant variation in pH was observed and drug content is 96.91% in F2 formulation after 3 months
where as drug content in F5 and F8 was 95.33 and 95.65 respectively.
In vitro Permeability study showed that permeation of formulations
(F2, F5 and F8) was comparable with each other.
CONCLUSION

RESULTS AND DISCUSSION

In the Preformulation studies the identification of drug by
Drug Invention Today Vol.2.Issue 5.May 2010

It was observed that hydroxypropyl methylcellulose (HPMC)

gel containing Diclofenac sodium (F2) produced better spreadability
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A Gupta et al. / Drug Invention Today 2010, 2(5),250-253

and consistency as compared to carbapol 934P gel (F5) and sodium
alginate gel (F8) formulation. The developed F2 gel showed good
homogeneity, no skin irritation, good stability and in vitro permeability. The HPMC forms water washable gel because of its water solubility and has wider prospects to be used as a topical drug delivery
system.

5.
6.
7.
8.
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Source of support: Nil, Conflict of interest: None Declared

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