Parthasarathy G et al.

/ Pharmacie Globale (IJCP) 2011, 6 (07)

1 Pharmacie Globale

(IJCP), Vol. 02, Issue 06

Available online at www.pharmacie-globale.info

PHARMACIE GLOBALE
INTERNATIONAL JOURNAL OF COMPREHENSIVE PHARMACY

FORMULATION AND CHARACTERIZATION OF TRANSDERMAL PATCHES OF NAPROXEN
WITH VARIOUS POLYMERS
G Parthasarathy*
1
, K Bhaskar Reddy
2
and V V Prasanth
3


1
Department of Pharmaceutics, R R College of Pharmacy, Bangalore, Karnataka, India.
2
Department of Pharmaceutics, Sri Venkateshwara College of Pharmacy, R V S Nagar, Chittoor, Andhra Pradesh, India.
3
Department of Pharmaceutics, Gautham College of Pharmacy, Bangalore, Karnataka, India.

Received: 2 April 2011; Revised: 22 May 2011; Accepted: 29 May 2011; Available online: 5 June 2011


INTRODUCTION
Naproxen is a nonsteroidal anti-inflammatory drug, which
relieves pain and swelling. It is used to treat headaches,
muscle aches, backaches, tendonitis, dental pain,
menstrual cramps, arthritis, or gout. This drug works by
blocking the enzyme that makes prostaglandins.
Decreasing prostaglandins helps to reduce pain and
swelling. The objective of the present study was to
overcome the harmful side effects of naproxen a non
steroidal anti-inflammatory drug [NSAID] which causes
severe gastro intestinal bleeding while taken orally.
1
The
usage of most of the NSAIDS by oral route associated with
potential disadvantages such as peptic ulceration and
gastric bleeding. This severe drawback creates a potential
need for development of transdermal patches of NSAIDS.
The major advantage of transdermal delivery system is the
ability to avoid first-pass metabolism and also to
circumvent the hostile environment of the gastrointestinal
tract.
2
In the present study an attempt was made to design
the Transdermal patches of Naproxen with various
proportions of Ethyl cellulose Polymer.

MATERIALS AND METHODS
Naproxen was obtained as gift sample from Brown & Berk,
Hosur. Ethyl cellulose (20cps) from Loba Chemie, Mumbai.
Hydroxy propyl methyl cellulose was procured from
Warne Hindustan Ltd, Hyderabad. The rest of the
ingredients and reagents used were of analytical grade.
Preparation of Naproxen transdermal patches
Transdermal patches of Naproxen were prepared with the
polymer Ethyl cellulose in various concentrations. The
matrix type patches were prepared by dispersing
*Corresponding Author:
G Parthasarathy
Department of Pharmaceutics, R R College of Pharmacy,
Bangalore - 560090, Karnataka, India.
Contact no: +91-9886431015; Email: mypartha@gmail.com
various proportions of Ethyl cellulose and Hydroxy propyl
methyl cellulose (10%W/V) in 30 ml of methanol. To this
dispersion weighed quantity of Naproxen (5%w/w based
on total polymer weight) is dissolved. This mixture was
stirred continuously by magnetic stirrer. After 1 hour of
stirring 10% w/w (based on total polymer weight) of
dibutylphthalate as plasticizer was added to the above
mixture as plasticizer. The stirring was continued for
another 1 hour. Then 5 ml of the sample was withdrawn
by using a pipette and slowly poured over a glass plate
covered with aluminium foil (5 x 5 cm). Care was taken to
avoid formation of air bubbles during the addition of
sample on the glass plate. The solvent was allowed to
evaporate at a controlled rate by placing an inverted glass
funnel over the glass plate. After 24 hours of drying at
room temperature, the film was removed and stored in a
desiccator.
Characterization of transdermal drug delivery system
The prepared films were characterized for thickness,
tensile strength and drug content. The thickness of the film
specimen was measured using a meter gauge. The tensile
strength of films was determined using the method
reported by Sadhana P Gupta et al
3
. The film was fixed to
the assembly, weights required to break the film was
noted and simultaneously film elongation was measured
with the help of a pointer mounted on assembly. Tensile
strength of the film was calculated using the formula:

Where a, b and L are the width, thickness and length of the
film and l is the elongation of film at break point. The film
thickness and tensile strength was recorded in Table 1.
The drug content was determined by weighing the
prepared film (1cm
2
) and dissolving in Ethanol. The drug
concentrations were noted in Table 2.
ABSTRACT
In the present study an attempt was made to design the transdermal drug delivery system of Naproxen with
Ethylcellulose and Hydroxy propyl methyl cellulose polymer in various concentrations. Tramsdermal films were
fabricated by matrix technique with various polymer proportions using dibutylphthalate as plasticizer. These
transdermal drug patches were characterized for their thickness, tensile strength, content uniformity, in-vitro
release. The release profiles were found to be varied with various concentrations of Ethylcellulose Polymer. The
sample of patches prepared with 2:8 and 8:2 ratios of Ethyl cellulose and Hydroxy propyl methyl cellulose shows
highest and lowest in-vitro release of Naproxen respectively.

Keywords: Naproxen, Transdermal Patches, Ethyl cellulose, HPMC, NSAID.
Research Article

ISSN 0976-8157
Parthasarathy G et al. / Pharmacie Globale (IJCP) 2011, 6 (07)
2 Pharmacie Globale

(IJCP), Vol. 02, Issue 06

Table 1. Characteristics of transdermal films
Formulation
code
Thickness
(mm)
Tensile Strength
(kg/cm
2
)
Drug content
(%/cm
2
)
NF-I 0.038 2.16 98.6
NF-II 0.04 2.6 98.9
NF-III 0.038 2.74 99
NF-IV 0.036 2.84 99.2
Table 2. Composition of transdermal films
Formulation
code
Composition of Transdermal films
Polymer Ratio
(10%w/v) Ethyl
cellulose: HPMC
Plasticizer %w/w
based on total
polymer weight
%(w/w) of Drug
based on total
polymer weight
NF-I 2:8 10 5
NF-II 4:6 10 5
NF-III 6:4 10 5
NF-IV 8:2 10 5

Preparation of mouse abdominal skin
Albino mice (6-8 weeks) are taken and sacrificed by excess
chloroform inhalation. The abdominal skin was carefully
separated, without damaging the dermis part. The inner
part of the skin was washed thoroughly to remove
adhering fat. The hair on the skin were carefully removed.
The full-thickness skin thus prepared was soaked in
distilled water at 60C for one minute, followed by the
epidermis was carefully removed with intact stratum
corneum. The epidermis was washed with distilled water,
dried in desicator, wrapped in aluminium foil and stored
at 41C. At the time of use, the epidermis was rehydrated
by immersing in water for 1 h at room temperature.
In-vitro drug skin permeation study
A specially designed rectangular diffusion cell (43
cm=12 cm
2
) as mentioned by Shaila lewis et al
4
was used
in the release study. The whole 12 cm
2
patch, along with
the mouse abdominal skin was used for release study. The
skin was mounted in such a way that stratum corneum of
the skin continuously remain in an intimate contact with
the transdermal patch in the donor compartment. The
membrane along with the patch, was firmly tied to the
diffusion cell, and was immersed in a beaker containing
200 ml of saline Phosphate buffer pH 7.4. The
experimental setup was placed on a thermostatically
controlled magnetic stirrer. The temperature was set at
372C. The content in the beaker were stirred with the
help of a magnetic bead, at a constant speed. The release
study was carried out for a period of 24 h. The diffusion
medium was continuously stirred with magnetic stirrer to
prevent the formation of concentrated drug solution
below the compartment. At each sampling time the
solution in the receptor compartment was completely
withdrawn and replaced with fresh and pre warmed
(372C) phosphate buffer solution. The absorbance of
withdrawn sample after suitable dilution was measured
by UV spectrophotometer at 331 nm. Samples collected
from placebo patches were used as blank.
The cumulative amount of the drug permeated per unit
skin surface area was plotted against Time. The slope of
the linear portion of the plot was estimated as the steady
state flux (J
ss
)
5,6

RESULTS AND DISCUSSION
Monolithic device of naproxen has been attempted.
Placebo films were studied for flexibility, clarity, elasticity
and ease of removal of films from the molds. The study
shows that the ethylcellulose and hydroxy propyl methyl
cellulose along with the plasticizer dibutylphthalate 10%
w/v of polymer weight was suitable for good flexibility
and elasticity. The composition of various transdermal
patches are shown in Table 1. Drug loaded films were
evaluated for physical and mechanical properties like
thickness uniformity and tensile strength and the results
are shown in Table 2.
The matrix transdermal drug delivery system bearing
naproxen was fabricated using various concentration
ratios of ethylcellulose and hydroxy propyl methyl
cellulose. The drug was uniformly distributed in the
polymer films and drug content was found to be 98.6% to
99.0% per cm
2
in the transdermal drug delivery system.
Films of lipophilic-hydrophilic polymers in various
proportions were studied. The combination of
ethylcellolose and hydroxy propyl methyl cellulose in a
ratio of 2:8 and 4:6 showed highest cumulative drug
release. Increasing the proportion of hydroxy propyl
methyl cellulose concentration increases the cumulative
amount release. From the release studies it was observed
that by increasing the proportion of Hydroxy propyl
methyl cellulose tend to increase the cumulative amount
of drug release. This increased release rate may be due to
higher hydrophilic nature of hydroxy propyl methyl
cellulose. Due to its high hydrophilicity it absorbs water
and swells resulting in the more release of drug from the
patches. The in-vitro release profile of naproxen patches
are shown in figure 1 & 2.
Figure 1. In-vitro release of Naproxen from films NF-I
() and NF- II ()

Figure 2. In-vitro release of Naproxen from films NF-III
() and NF- IV ()

The decrease in drug release rate from films containing
more lipophilic polymer combination (6:4 and 8:2) of
Ethylcellulose and Hydroxyl propyl methyl cellulose (NF-
III and NF-IV) in comparison to films containing more
hydrophilic polymer combination (2:8 and 4:6) of
Ethylcellulose and Hydroxyl propyl methyl cellulose (NF-I
and NF-II) may be attributed to the relatively hydrophobic
nature of polymer which have less affinity for water, this
result in decrease in thermodynamic activity of the drug in
the film and decreased drug release. The results are shown
in figure 2. The cumulative amount of drug release versus
time profile is shown in figure 1 and 2. The cumulative
amount of the drug permeated per unit skin surface area
was plotted against time and the slope of the linear
Parthasarathy G et al. / Pharmacie Globale (IJCP) 2011, 6 (07)
3 Pharmacie Globale

(IJCP), Vol. 02, Issue 06

portion of the plot was estimated as the steady state flux
(Jss) From above studies it can be concluded that the
polymeric matrix type transdermal films of Naproxen
prepared with different grades and ratios of polymers
holds potential for transdermal delivery. The cumulative
drug release verses time plot gives a linear curve, this
supporting the test products were suitable for
transdermal patches.

CONCLUSION
From the above discussion it can be concluded that
naproxen that releases from the transdermal patches of
NF-III (EC-HPMC 6:4) and NF-IV (EC-HPMC 8:2) showed
prolonged drug release. The high proportion of
hydrophobic polymer ethyl cellulose is responsible for
sustaining the drug release. This research work highlights
the best combination of drug and polymer concentrations
and also provides a rational guideline for formulating
controlled release transdermal patches. The formulated
transdermal delivery system of Naproxen can be a best
alternate to the oral formulations for effectiv therapy of
inflammatory conditions.

ACKNOWLEDGMENT
The authors are grateful to R R College of Pharmacy,
Bangalore for providing research facilities and Brown &
Berk, Hosur, India for providing gift samples of the drug to
carry out this research work.
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