Kansagra Hemang et al.

IRJP 2012, 3 (11)

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY
www.irjponline.com ISSN 2230 – 8407
Research Article

FORMULATION AND EVALUATION OF TRANSDERMAL PATCH OF SERTACONAZOLE NITRATE

Kansagra Hemang1*, Mallick Subrata2, Karigar Asif3
1
Biodeal Pharmaceuticals Pvt. Ltd., Village Saini Majra, Nalagarh, 174101, Solan, Himachal Pradesh, India
2
Department of Pharmaceutics, SOA University, Bhubaneswar - 751003, Orissa, India
3
Maratha Mandal’s College of Pharmacy, Belgaum 590016, Karnataka, India

Article Received on: 04/09/12 Revised on: 01/10/12 Approved for publication: 12/11/12

*E-mail: hemangpatel.d@gmail.com
ABSTRACT
The present work was designed to develop suitable transdermal matrix patch of sertaconazole nitrate, which is of the imidazole class used for
antifungal medication, using Ethyl cellulose (EC), Polyvinyl pyrrolidone (PVPK-30) and Dibutyl phthalate. The aqueous insolubility of the drug
inspires for the formulation of controlled release transdermal patches. Different batches developed using Ethyl cellulose and Polyvinyl pyrrolidone in
different ratios by solvent evaporation technique. Drug excipient interaction study was further carried out using Fourier Transform Infrared (FTIR)
spectroscopic technique. Physical evaluation performed such as moisture content, moisture uptake, thickness and folding endurance. In vitro diffusion
studies were performed using cellulose nitrate membrane (pore size 0.45μ) in modified Franz’s diffusion cells in buffer of pH 7.4. Permeation studies
illustrated that the ratio of polyvinyl pyrrolidone and ethyl cellulose 1:5 shows good controlled release. Higuchi and Korsmeyer-Peppas models were used for
optimizing the formulation.
Keywords: Polyvinyl pyrrolidone, Ethyl cellulose, Sertaconazole nitrate, modified Franz’s diffusion cell, transdermal patches, Dibutyl phthalate and
antifungal agents.

INTRODUCTION nitrate. The polymers used for the preparation of matrix

In the recent years, considerable attention has been are polyvinyl pyrrolidone (PVPK-30), ethyl cellulose (EC)
focused on the development of new drug delivery and dibutyl phthalate as plasticizer.
systems. Previously, the most commonly applied systems
were topically applied creams and ointments for MATERIALS AND METHODS
dermatological disorders. Conventional dosage forms Sertaconazole nitrate, Polyvinyl pyrrolidone (PVPK-30)
usually produce wide ranging fluctuation in were supplied as a gift sample from Biodeal
bioavailability of drug leading to the requirement of Pharmaceuticals Pvt. Ltd., (Himachal Pradesh, India),
developing controlled release drug delivery system. Ethyl cellulose, n-dibutyl phthalate and chloroform were
Factors such as repetitive dosing and unpredictable purchased from S.D. Fine Chemicals, Mumbai, India. Tris
absorption lead to the concept of controlled drug buffer was purchased from RFCL, New Delhi, India and
delivery system or therapeutic system1. Sodium Lauryl Sulfate (SLS) was purchased from
Transdermal patches are innovative drug delivery systems Qualigens Fine Chemicals, Navi Mumbai, India. All
intended for skin application to achieve a systemic effect. chemicals, solvents and reagents were used of either
These are medicated adhesive patches that are placed on pharmacopoeial or analytical grade.
the skin to provide clinical benefits like controlled Characterization & Compatibility Study of drug and
release of the drug, and produce a steady blood-level excipients
profile, leading to reduced systemic side effects and FTIR spectra of pure sertaconazole nitrate and physical
improved efficacy over other dosage forms2. Transdermal mixture of drug and excipients were recorded on FTIR-
patches offer advantages such as maintenance of constant 8400S, Shimadzu, (Tokyo, Japan). Potassium bromide
and prolonged drug level, reduced frequency of dosing, pellet method was employed and background spectrum
minimization of inter and intra patient variability, self was collected under identical situation. The mixture of
medication, leading to patient compliance3-7. sertaconazole nitrate, polyvinyl pyrrolidone and ethyl
Transdermal systems provide drug systemically at a cellulose was taken and pellet was prepared for
predictable rate and maintain the rate for extended spectroscopic studies. Each spectrum was derived from
periods of time thus eliminating numerous problems single average scans collected in the region of 400-
associated with oral products such as unpredictable or 4000 cm-1 at spectral resolution of 4 cm-2 and ratio against
reduced bioavailability, enhanced first pass hepatic background interferogram. Spectra were analyzed by
metabolism, relatively short residence time, dose software supplied by Shimadzu1.
dumping and dosing inflexibility3. Preparation of transdermal patches
Sertaconazole nitrate is an imidazole/triazole type antifungal Matrix type transdermal patches composed of different
agent8. Sertaconazole nitrate has a specific mode of action. ratios of Ethyl cellulose and PVPK-30 were prepared by
It interacts with the 14-a demethylase, a cytochrome P- solvent evaporation technique in a petri dish. The bottom of
450 enzyme necessary to convert lanosterol to ergosterol. the ring was wrapped with aluminum foil on which backing
As ergosterol is an essential component of the fungal membrane was cast by pouring 4% w/v polyvinyl alcohol
cell membrane, inhibition of its synthesis results in solution followed by drying at 60oC for 6h. Dibutyl phthalate
increased cellular permeability causing leakage of cellular was incorporated as a plasticizer at 30% w/w of dry
contents8. The present study was undertaken to formulate weight of polymer. Backing membrane was casted by
the matrix type transdermal patches of sertaconazole pouring and allowing to evaporate 4% aqueous solution

Page 109
 Kansagra Hemang et al. IRJP 2012, 3 (11)
of polyvinyl alcohol in petri dish at 60oC for 6h. The matrix 40oC for 2h with inverted funnel on the dispersion to
was prepared by pouring the homogenous dispersion of drug achieve a drug polymer matrix patch. The patches were
with different blends of ethyl cellulose with PVPK-30 in again dried at 60oC for 30 min for complete drying. The dry
chloroform on the backing membrane in petri dish. The patches were kept in dessicators until use1-3 [Table 1].
above dispersion was evaporated slowly and uniformly at
Table 1: Composition of Formulation
Formulation Polymeric Ratio of Total weight of Drug %w/w Plasicizer dibutyl Solvent
Blend Polymer (W/W) polymer in mg of polymer phthalate system
F1 PVP:EC 1:1 600 10 30% Chloroform
F2 PVP:EC 1:2 600 10 30% Chloroform
F3 PVP:EC 1:3 600 10 30% Chloroform
F4 PVP:EC 1:5 600 10 30% Chloroform
F5 PVP:EC 2:3 600 10 30% Chloroform

Solubility measurement silica at room temperature for 24h. The films were
Solubility of sertaconazole nitrate was determined at weighed again and again individually until it showed a
several values of pH, viz., 4.0, 5.0, 6.0, 7.4, 8.0, and constant weight. The percentage of moisture content was
9.0. Excess of sertaconazole nitrate was added to 10 mL calculated as the difference between initial and final
of buffer solutions. weight2-6.
At each level, the samples were stirred in a conical % Moisture content= Initial weight – Final weight/Initial
flask for 24h at 37oC. The suspension were filtered weight x 100
using a 0.45 micron Whatman filter paper. The Folding endurance
concentration of sertaconazole nitrate in the filtrate was Folding endurance of patches was determined by
determined spectrophotometrically by measuring at 303 nm 1. repeatedly folding a small strip of film (2cm x 2cm) at
Partition coefficient of drug in octanol/water system the same place till it is broken. The number of time the
The partition coefficient of the drug was determined by film could be folded at the same place without breaking
taking equal volume of 1-octanol and aqueous solution was the folding endurance value2-6.
in a separating funnel. In case of water soluble drugs, a Flatness
drug solution of 25μg/ml was prepared in distilled water Longitudinal strips were cut out from each film, one
and in case of water insoluble drugs, a drug solution of from the center and two from either side. The length of
25μg/ml was prepared in 1-octanol. Twenty-five each strip was measured and the variation in flatness was
milliliters of this solution was taken in a separating measured by determining percent constriction, considering
funnel and shaken with equal volume of 1-octanol/water 0% constriction is equivalent to 100% flatness.
system for 30 min and allowed to stand for an hour. The % Constriction = l1-l2/ l2 x 100
mixture was then centrifuged at 2000 rpm for 10 min and l1= initial length of each strip.
concentration of drug in each phase was determined l2 = final length of each strip.
spectrophotometrically by measuring absorbance at 303 In vitro diffusion study
nm. The partition coefficient (Kp) was calculated from the Franz’s diffusion cell was used for the study of in vitro
following equation1. release patterns of the prepared patches. The diffusion
Partition coefficient (Kp) = Conc. of drug in organic medium is prepared of buffer of pH 7.4. A cellophane
phase/Conc. of drug in aqueous Phase membrane is used as a barrier between the donor and receptor
Physicochemical properties of the films compartment. The films were placed between the donor and
Thickness receptor compartment in such a way that the drug
The thickness of the patch was determined using digital releasing surface faced the receptor compartment. The
vernier calliper (Mitutoyo, Tokyo, Japan), recording receptor compartment was filled with the buffer having
mean of 5 determinations2-6. pH 7.4 and a small bar magnet was used to stir the
Weight variation medium with the help of a magnetic stirrer. The temperature
Each film was weighed individually and average weight of of the diffusion medium was maintained and controlled
three films was found out. at 37oC± 1oC by a thermostatic arrangement. A sample of
Percent moisture absorption 5ml was withdrawn at predetermined intervals, being
The percent moisture absorption test was carried out to check replenished by equal volumes of diffusion medium.
the physical stability and integrity of the films at high humid Withdrawal of samples was carried out for a period of 24h.
conditions. In the present study the moisture absorption The drug concentration in the sampled diffusion medium
capacity of the films were determined in the following was determined spectrophotometrically and was calculated
manner. with the help of a standard calibration curve and the
The films were placed in the humidity chamber, keeping data was shown in Figures2.
the humidity inside the chamber at 75% R.H . After 3 Data analysis
days the films were taken and weighed. The percentage The pharmaceutical dosage forms that do not
moisture absorption of three films was found by disaggregate and release the drug slowly could be
applying following formula2-6. represented by a zero- order kinetic equation. Analysis of
% Moisture absorption= Final weight – Initial weight/Initial drug release from transdermal system must be performed
weight x 100 with a flexible model that can identify the contribution to
Percent moisture content overall kinetics. Dissolution data was treated with different
The prepared films were marked, then weighed release kinetic equations.
individually and kept in a dessicator containing activated

Page 110
 Kansagra Hemang et al. IRJP 2012, 3 (11)

% Release of Sertaconazole nitrate % Release of Sertaconazole nitrate

90 80
75.04255
80 79.89362 70 54.59574
70 59.97872 60

% Drug Release
% Drug Release

60
52.12766 50 46.93617
50
34.17021 40 31.29787
40
30
30 26.51064 24.21277
20 20
17.3617 15.44681
10 10.89362 10 9.191489
0 0 0 0
0 5 10 15 20 25 30 0 5 10 15 20 25 30
Time in Hour Time in hour

Figure -1 Drug release from formulation F1 Figure -2 Drug release from formulation F2

% Release of Sertaconazole nitrate % Relese of Sertaconazone nitrate

100
89.2766 80
80 70 60.65957 71.21277
66.44681
60
% drug release

% drug release
60 56.89362
43.38298 50 38.06383 47
40 Series1 40
34.44681 30 30.3617
24.97872
20 18.7234 20 21.2766
13.61702
10
0 0
0 0
0 5 10 15 20 25 30
0 5 10 15 20 25 30
Time in hour
Time in Hour

Figure -3 Drug release from formulation F3 Figure -4 Drug release from formulation F4

% Release of Sertaconazole nitrate

100
92.93617021
76.27659574
80
67.21276596
% release

60

40 43.68085106
32.95744681
20 22.23404255
14.46809
0 0
0 5 10 15 20 25 30
Time in hour

Figure -5 Drug release from formulation F5

Figure 1 to 5 showing the % of sertaconazole release from the formulated patches

Chart showing % moisture Chart showing thickness of

content of patch different formulation
0.2

3.5 0.195
3
0.19
2.5
% Mois ture 2 Thickness 0.185
content 1.5
0.18
1
0.5 0.175
0
0.17
F1 F2 F3 F4 F5
F1 F2 F3 F4 F5
Formulation code
Formulation code

Figure -6 Showing thicknesses of patches Figure -7 Showing Endurances of patches

Page 111
 Kansagra Hemang et al. IRJP 2012, 3 (11)

C h a r t s h o w in g f o ld in g Chart showing % of
endurance of patch moisture uptake
160
140
6
120
5
Folding 100
4
endurance 80 % of moisture
60 3
uptake
40 2
20 1
0 0
F1 F2 F3 F4 F5 F1 F2 F3 F4 F5
Formulation code Formulation code

Figure -8 % of moisture content of patches Figure -9 % of moisture uptake patches

Figure-10 IR spectrum of sertaconazole nitrate Figure-11

Table 2: Evaluation of transdermal patches of Sertaconzole nitrate

Formulation Thickness Folding %Moisture %Moisture Flatness
Endurance Content Uptake
F1 0.18 ± 0.03 104 ± 3 2.73 ± 0.14 4.98 ± 0.25 100 %
F2 0.18 ± 0.02 118 ± 4 2.86 ± 0.42 4.77 ± 0.36 100%
F3 0.19 ± 0.04 129 ± 2 2.34 ± 0.21 5.58 ± 1.03 100%
F4 0.19 ± 0.03 152 ± 2 2.68 ± 0.34 5.22 ± 0.53 100%
F5 0.20 ± 0.02 98 ± 3 3.16 ± 0.32 4.03 ± 0.98 100%

Zero-order release equation variation, percent moisture absorption, percent moisture

Q = kot content, flatness and folding endurance. The release
Higuchi’s square root of time equation pattern of formulations were studied in Franz’s diffusion
Q = kHt1/2 apparatus using cellophane membrane.
First-order release equation The thickness of the films varied from 17 to 20 mm. The
Log Qt = LogQo + Kt/2.303 minimum standard deviation values assumed that the
Korsmeyer-Peppas equation process used for preparing the drug delivery system is
F = (Mt/M) = Kmtn capable of giving reproducible result.
Where Q is the amount of drug release at time t; Mt is Moisture content and moisture uptake can cause
drug release at time t; M is the total amount of drug in significant changes in properties such as reduced
dosage form; F is fraction of drug release at time t; Ko crushing strength, increased pore diameter in the patches
is zer-order release rate constant; KH is Higuchi square containing polymer. But the moisture content in our
root of time release rate constant; Km is a constant preparations was found to be low, and it varied very
dependent on geometry of dosage form; and n is little in the formulations. The little moisture content
diffusion exponent indicating the mechanism of drug helps the formulations to be stable and prevents them
release. If the value of n is 0.5, it indicates fickian from becoming a completely dried, brittle product. Low
diffusion; if between 0.5 and 1.0, anomalous transport; moisture uptake also protects the materials from
1.0 indicates case-ll transport; and higher than 1.0, super microbial contamination and avoids bulkiness of the
case-ll transport1. patches.
In order to evaluate the flexibility the film were
RESULTS AND DISCUSSION subjected to folding endurance. The values in the range
In the present study efforts were made to prepare that prepared films were observed batches having
transdermal patches of sertaconazole nitrate by using capability to withstand the mechanical pressure along
different ratios of polymers such as Polyvinyl pyrrolidone with good flexibility.
(PVP K-30) and ethyl cellulose. Here dibutylphthalate is The diffusion studies of patches containing different
used as a plasticizer. ratios of polymers were done using Franz’s diffusion
The prepared formulations were subjected to various cell. The revealed data shows that the drug release
physicochemical characteristics such as thickness, weight pattern of formulation 4 shows drug release in a

Page 112
 Kansagra Hemang et al. IRJP 2012, 3 (11)
controlled manner, as it fits into the Kosmeyers-peppas containing ethyl cellulose- povidone as film former, Asian Journal of
Pharmaceutics, 2008.
rule. The formulation 4 shows cumulative release of drug of
2. Prashant MS, Suniket F, Auimash KD. Evaluation of Polymerised Rosin
71.21%. for the Formulation and Development of Transdermal drug delivery
system; A technical note ,AAPS Pharma Sci Tech , 2005; 6: 81.
CONCLUSION 3. Reddy AB, Invitro Characterization and Evaluation of Transdermal drug
Formulation 4 was found to be the best among all batches delivery system for Metoprolol Tartarate, JPRHC, 2008; 2: 325-329.
4. Lewis S, Panday S, Udupa N, Design and Evaluation of Matrix type and
because of its consistent release rate and extent of drug Membrane controlled Transdermal delivery System f Nicotine suitable
release. for use in Smoking Cessation, Indian Journal of Pharmaceutical
The formulation 4 has achieved the object to extended release Sciences, 2006.
5. Shinde AJ, Gorola KC, More HN, Development and Characterization
reduced frequency of administration, avoids the first pass
Transdermal Therapeutics System of Tramadol Hydrochloride, Asian
effect and thus may improve the patient compliance. Journal of Pharmaceutics, 2008.
6. Pintu D, Damodharan N, Mallick S, Mukherjee B, Development and
ACKNOWLEDGEMENT Evaluation of Nefopan Transdermal Matrix Patch System in Human
Volunteers, PDA Journal of Pharmaceutical Science and Technology,
We are thankful to Biodeal Pharmaceuticals Pvt. Ltd. for
2009; 63: 537 – 546.
their support and kind cooperation for my work. 7. Chang SR, Liang F, Lei L, Qiang W, Sihai L, Ligang Z, Zhongee H,
Design and Invivo Evaluation of an Indapamide Transdermal Patch,
REFERENCES Intrenational Journal of Pharmaceutics, 2009; 37: 129 – 135.
1. Sadashivaiah R, Dinesh BM, Uma A. Patil BG, Raghu KS. Design and 8. http://www.drugbank.co/drugs/DBO1153.
in-vitro evaluation of Haloperidol Lactate transdermal patches

Source of support: Nil, Conflict of interest: None Declared

IRJP is an official publication of Moksha Publishing House. Website: www.mokshaph.com. All rights reserved.

Page 113