ISSN No:2321-8630, V 1, I 1, 2014

Journal Club for Pharmaceutical Sciences (JCPS)

Manuscript No: JCPS/RES/2014/8, Received On: 01/08/2014, Revised On: 05/08/2014, Accepted On: 08/08/2014

RESEARCH ARTICLE
Development and Characterization of Transdermal Patch for Controlled Release of
Fluocinolone Acetonide
Joshi DM, Patel S, Moin MK, Patel AK, Patel VM
Pharmaceutics Department, A.P.M.C. College of Pharmaceutical Education and Research,
Motipura, Himatnagar 383001, Gujarat
ABSTRACT
The purpose of this research was to design matrix type of transdermal patch of Fluocinolone
acetonide. Polyvinyl pyrrolidone K-30 (PVP K-30) and polyvinyl alcohol (PVA) was used in fixed
ratio of 2:5 throughout the study and was concluded from preliminary study. Single layer matrix was
chosen for providing 24 hrs of continuous release. Solvent casting method was used for preparation
of patches. 3 level 2 factor full factorial designs was applied for optimization of batch for optimising
amount of poly ethylene oxide ( Polyox WSR 1105) and Propylene Glycol (PG). The effects of
polymer type, polymer ratio, permeation enhancer, plasticiser on drug release were evaluated by invitro release using treated cellophane paper by using Franz diffusion cell. In addition various other
characterizations like appearance, folding endurance, tensile strength, % moisture content, % drug
content, thickness, flatness was done. ANOVA for Response Surface Quadratic Model for %
cumulative drug release and % moisture content responses applied and found significant for
optimization. From the contour plot and over lay plot range of various amounts of PG and Polyox
found to provide desired responses. Validity of equation was checked by checkpoint batch was true
for present work.
KEYWORDS
Transdermal drug delivery system (TDDS), Fluocinolone acetonide, solvent casting method, antiinflammatory.
INTRODUCTION

problems and complications. The design of

Conventional systems of medication which

conventional dosage form, whether a tablet, an

require multi dose therapy have numerous

injection, to deliver the right amount of

*Address for Correspondence:

Mihir D Joshi
Pharmaceutics Department,
A.P.M.C. College of Pharmaceutical
Education and Research, Motipura,
Himatnagar 383001, Gujarat, India.
E-Mail Id: maruti.pharm@gmail.com
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medicine at the right target site becomes

complicated,

so

controlled

release

drug

delivery system, a novel drug delivery

approach evolves, which facilitates the drug
release into systemic circulation at a pre-

21

determined rate. Controlled drug release can

suppress the symptoms of disease, e.g. -

be achieved by transdermal drug delivery

pruritus, itching, dryness of skin etc. FA has

systems (TDDS) which can deliver medicines

very low half-life so it is desirable to increase

via the skin portal to systemic circulation and

frequency of dosing for optimum drug plasma

also provide local effect at a predetermined

concentration.

rate over a prolonged period of time.1

formulation shall be prepared as FA is highly

Controlled drug delivery (CDD) has become

potent so devoid of overdosing. By preparing

important in the pharmaceutical industry in

patch formulation occlusion provides moisture

recent years. The pharmacological response,

to skin which is further advantageous for skin

both the desired therapeutic effect and the

dryness symptom and may help to provide

undesired adverse effect, of a drug is

aesthetic feel for being in society.

dependent on the concentration of the drug at

The aims of the present study were to prepare

the site of action, which in turn depends upon

matrix type transdermal patches of FA using

the dosage form and the extent of absorption

povidone, polyvinyl alcohol and Polyox WSR

of the drug at the site of action.

1105 polymers and study the in-vitro diffusion

The potential of using the intact skin as the

behaviour of prepared matrix type transdermal

port of drug administration to the human body

patch formulations. The purpose was to

has been recognized for several decades, but

provide the delivery of the drug at a controlled

skin is a very difficult barrier to the ingress of

rate.

The

controlled

release

materials allowing only small quantities of a

drug to penetrate over a period of time. There
are main pathways by which drugs can cross
the skin and reach the systemic circulation are
trans cellular pathway, intercellular route,
follicular route.2
TDDS also known as patches are dosage
forms designed to deliver a therapeutically
effective amount of drug across a patients
skin. Several TDDS containing drugs such as
clonidine,

estradiol,

fentanyl,

nicotine,

nitroglycerin, oxybutynin and scopolamine are

available in the United States and other
countries.3
FA is highly potent corticosteroid drug, can be
used for eczema disease treatment and to

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MATERIALS & METHODS

Fluocinolone

acetonide

(Tripda

Pharmaceuticals, Ahmedabad) and Polyox

WSR 1105 (Colorcon, Verna, Goa) were
obtained as gift

sample. Povidone and

polyvinyl alcohol (MCC laboratory chemicals,

Ahmedabad),

propylene glycol (S.D.Fine

Chemicals,

Mumbai),

consumers,

Ahmedabad)

Ethanol
were

(Ureca
obtained

commercially. All the chemicals were used as

received without any further treatment and
purification.
From the preliminary trials for selection of
polymer and plasticiser the ratio for the PVP
K-30 and PVA was taken as constant in 2:5

22

Development and Characterization of Transdermal Patch for Controlled Release of Fluocinolone Acetonide
and various amounts of Polyox WSR 1105 and
PG was selected as independent factors for 3

Physicochemical Compatibility of Drug and

level 2 factor full factorial designs. As the

Excipients 4

dependent factor % cumulative drug release

The FTIR of pure drug and physical mixture

(at 24 hrs) and % moisture content were taken.

of formulation ingredients of optimized patch

were measured using Fourier Transform

Method of preparation of Patch

Infrared Spectrophotometer. The amount of

Transdermal patches containing FA and

each ingredient in the physical mixture was

various amounts of propylene glycol and

same as that in the optimized batch. The pure

Polyox WSR 1105 were prepared by solvent

drug and formulation mixture were than

casting method. The detail composition of

separately mixed with IR grade KBr and liquid

various pathes is furnished in table. Accurately

holder respectively. This mixture was then

weighted drug were dissolved in ethanol, than

scanned over a wave number range 4000 to

selected ratio of polymer were weighted. PVP

400 cm-1

K-30 was dissolved in Ethanol. PVA was then

Physical Appearance 5

stirred with magnetic stirrer in cold water. The

All the transdermal patches were visually

temperature

to

inspected for colour, clarity, flexibility and

solubilised, then after cooling Polyox was

smoothness. It is qualitative test which is

added to PVA solution with continuous

mentioned by + and as the number of +

stirring. PG was added to above solution. The

increases the appearance was considered as

alcoholic solution was added to aqueous

better.

solution stirred for 30 min. The mixture

Thickness 6

solution was then set aside for 20 min to

Patch

release air entrapment. Then on the one side

Micrometre screwguage and recorded. Results

silicone coated release liner the solution was

were

poured. After 60 min at room temperature the

measurements in that 4 corners and the centre

backing membrane was put on patch matrix

of each patch.

and given rolling press for PSAs (pressure

Weight Uniformity 6

sensitive adhesives) to stick with backing

Three randomly selected patches of each

membrane.

formulation patch were weighed individually

The dried patches were cut in to required size

and their average weights were calculated.

(53=15 cm2). The patches were packed in

Folding Endurance 7

aluminium foil and store in desiccator till

It was determined by repeatedly folding a

study. All the formulas shown in table 1 were

small strip of films at the same place till it

used for 80 cm2 patch preparation.

broke. The number of times, the films could be

was

gradually

increased

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thickness

reported

was

as

the

determined

mean

using

of

five

23

folded at the same place without breaking

Drug Content Analysis 6

gave the value of folding endurance.

For drug content determination, the total

Tensile Strength 8

content of transdermal patch was placed in a

The tensile strength should be determined by

100 ml volumetric flask and dissolved in

using a modified pulley system. Weight was

phosphate buffer pH7.4. The solution was

gradually increased so as to increase the

filtered through a Whatman filter membrane

pulling force till the patch broke. The force

(0.45m) prior to spectrophotometric drug

required to break the film was consider as a

analysis at 240 nm (Shimadzu, model UV-

tensile strength and it was calculated as

1700 PC, Kyoto, Japan).

kg/cm2.
Percentage Elongation Break Test 1

In Vitro Diffusion Studies (Drug release

The percentage elongation break is to be

profile) 9

determined by noting the length just before the

In vitro permeation studies were performed by

break point, the percentage elongation can be

using a modified Franz diffusion cell across a

determined

cellulose membrane using phosphate buffer

from

the

below

mentioned

formula.
Elongation percentage = (L1-L2) / L2
100

pH 7.4 as the in vitro study fluid in the

receptor compartment. The polymeric film
was placed on the cellulose membrane. The
holder contains the cellulose membrane. The

Where, L1is the final length of each

strip and
L2 is the initial length of each strip.

formulation was then placed on the receiver

compartment of the modified diffusion cell
containing phosphate buffer pH 7.4. The donor
and receiver compartments were kept in

Percentage Moisture Content 1

immediate contact by wrapping para film at

The prepared films are to be weighed

the junction. The temperature of the diffusion

individually and to be kept in a desiccator

cell was maintained at 32 0.5-C by a

containing fused calcium chloride at room

circulating water jacket. The whole assembly

temperature for 24 hrs. After 24 hrs, the films

was kept on a magnetic stirrer, and solution in

are to be reweighed and determine the

the receiver compartment was constantly and

percentage moisture content from the below

continuously

mentioned formula.

experiment

Percentage moisture Content = [(Initial

weight- Final weight) / Final weight]
100

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stirred
using

throughout

magnetic

the

beads.

The

samples were withdrawn (1 mL each time) at

different time intervals (up to 24 Hrs.) and an
equal amount of phosphate buffer pH 7.4 was
replaced each time. The intensities of samples

24

Development and Characterization of Transdermal Patch for Controlled Release of Fluocinolone Acetonide
were measured spectro photometrically. The

centimetre at each time interval was calculated

amount

and plotted against time.

of drug

permeated

per

square

Table: 1 Formulation batches of transdermal patches of Fluocinolone acetonide

Formulation

FA(mg)

PVA(gm) PVPK30

Polyox

PG

Ethanol

Water

F1

2.0

0.5

0.2

0.10

0.3

10

F2

2.0

0.5

0.2

0.25

0.3

10

F3

2.0

0.5

0.2

0.40

0.3

10

F4

2.0

0.5

0.2

0.10

0.6

10

F5

2.0

0.5

0.2

0.25

0.6

10

F6

2.0

0.5

0.2

0.40

0.6

10

F7

2.0

0.5

0.2

0.10

0.9

10

F8

2.0

0.5

0.2

0.25

0.9

10

F9

2.0

0.5

0.2

0.40

0.9

10

and chemical interaction between drug and

deviation (n=3). The results show as the

excipients used. Infrared spectra of FA drug

amount of Polyox and PG increases the

and formulation. From the figure , it was

thickness and weights were increased. Lesser

observed that there were no change in these

the standard deviation provide the assuredly of

main peak in IR spectra of formulation, which

reproducibility of procedure and product

shows there were no physical interactions

quality. Thickness was varied from 310-400

because of some bond formation between the

micron.5, 11

drug and polymers.4

The batches had folding endurance >150 can

Patches were visually inspected for colour,

be accepted for the formulation. Here the

clarity, flexibility and smoothness and batch

amount of Polyox increases the folding

F2, F4, F5 were found best in all inspection

endurance decreases might be due to loosen

for visual inspection. Results shows as the

the matrix inter linkage because of swelling

amount of Polyox increases the appearance

property. But as the amount of PG increase the

gone bad for features. It may be due to higher

folding endurance gone higher in number due

swelling property and more the cross linkage

to flexibility plasticizer property.5, 12, 13

more the moisture content. As the amount of

Polyox increases the color gone opaque and

Tensile strengths were found from result

clarity reduces.4, 10, 11

0.190-0.320 kg/cm2.

All the patches were examined for thickness ,

polymer increases the % moisture content

weight uniformity and folding endurance as

increases. Here the % moisture content 10-

repeated each for 3 times so as standard

13% was found optimum for adhesion and

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As the hydrophilic

25

other

properties.

Adhesion

was

simply

By over laying the responses the over lay plot

evaluated by thumb tack test which is

provide the optimal area of factor can be used

qualitative. 6,14,15

for desired response.

Drug content was found within limits (96104%)

16, 17, 18

for all formulations. And tests

were

done

by

From the overlay plot one check point batch

was prepared and validity of equation was

using

Shimadzu

1700

Spectrophotometer.

checked

for

both

response

and

found

minimum relative error 2.42 for % cumulative

By applying ANOVA for Response Surface

release (at 24 hrs.) and 0.84 for % moisture

content.

Quadratic Model by Design Expert (Version

8) for % cumulative drug release (at 24 hrs.) pvalue was found 0.0109 which was significant

From the results of % cumulative drug release

(at 24 hrs.) the Batch F2 show maximum
release 88.092.26 % and batch F9 shows

at 0.05> t-test. And ANOVA for Response

Surface Quadratic Model for % moisture
content p-value was found 0.0017 significant.

61.411.1 lowest release of drug for in-vitro

release study. % Cumulative drug release (at
24 hrs.) decreases as the amount of Polyox
increase as the thickness of the formulation

Contour plot provide graphical representation

of desired values of response from the factor

decreases the amount of drug available for

release was decreases due to more the
torturous path and the release was found slow.

values.

Fig 1a:FTIR of pure drug FA

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26

Development and Characterization of Transdermal Patch for Controlled Release of Fluocinolone Acetonide

Fig 1b : FTIR of Formulation

Table: 2a Physicochemical Characteristics of Patch

Batch Code

F1
F2
F3
F4
F5
F6
F7
F8
F9

Physical
appearance

++
+++
++
+++
+++
+
++
++
+

Thickness
(m)
(n=3)

31010
3507.56
3805.77
3205.90
3607.88
3905.77
32010
3605.77
40010

Weight Uniformity
(mg)
(n=3)

5860.98
6941.96
8561.74
6040.85
7221.45
9252.06
6351.61
7801.56
9862.12

Folding
Endurance
(n=3)

1973.14
1652.12
1261.8
2305.65
1742.77
1433.1
2106.21
1904.26
1397.83

Table: 2b Physicochemical Characteristics of Patch

Batch Code

Tensile
strength
(kg/cm2) (n=3)

% Elongation
at break (n=3)

% Moisture
content (n=3)

% Drug
content
(n=3)

F1
F2
F3
F4
F5
F6
F7
F8
F9

0.3200.19
0.2800.32
0.2300.20
0.3050.15
0.2550.22
0.1900.12
0.2870.14
0.2430.29
0.1950.13

14.210.57
15.090.34
15.980.45
18.240.32
19.340.25
20.220.13
24.210.34
25.110.56
25.8714

4.140.68
10.11.15
21.21.88
5.20.87
12.11.2
22.32.32
6.80.68
15.20.95
23.11.45

96.241.23
98.461.05
98.050.97
99.140.78
97.351.18
100.241.86
96.970.88
98.231.13
95.781.54

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27

Table: 2c Release Profile of Factorial Batch F1 to F5

% Cumulative Drug Release

Time
(Hrs)

F1

F2

F3

F4

F5

7.190.71

7.900.85

7.190.96

7.191.08

8.620.91

9.670.98

10.421.02

10.390.85

11.110.77

11.171.26

14.081.73

14.830.98

15.551.04

15.580.63

14.861.63

18.591.56

20.061.02

19.371.36

17.931.71

20.061.54

22.371.46

23.880.89

23.841.85

21.621.63

23.880.53

27.572.48

29.071.32

29.072.12

26.820.56

29.071.88

32.112.4

34.330.86

32.891.68

31.361.12

33.612.01

35.900.86

38.151.42

37.371.63

34.431.75

37.401.66

40.371.02

42.631.23

41.871.96

36.711.68

41.871.44

10

44.882.62

47.130.96

44.952.16

41.121.45

45.662.03

11

49.390.84

51.641.56

48.671.85

44.191.85

49.421.85

12

52.461.53

57.591.98

53.862.45

47.201.75

52.462.45

18

68.401.65

75.092.16

69.182.46

64.582.37

69.122.48

24

81.331.54

88.092.26

79.211.75

78.292.06

79.932.56

Time
(Hrs)
0
1
2
3
4
5
6
7
8
9
10
11
12
18
24

Table: 2d Release Profile of Factorial Batch F6 to F9

% Cumulative Drug Release
F6
F7
F8
0
0
0
8.621.36
7.191.32
7.902.01
10.451.45
9.670.54
11.862.10
14.110.98
15.520.87
14.890.32
19.301.65
20.811.2
18.621.02
23.132.45
23.911.6
22.371.86
27.601.63
27.632.2
26.850.86
30.671.12
31.391.45
29.920.68
34.391.23
35.150.96
33.642.45
37.431.23
38.181.25
36.680.96
41.162.42
43.342.21
40.411.01
44.911.23
47.890.86
44.160.77
48.671.68
50.241.52
47.202.3
61.772.01
56.801.3
58.833.12
70.261.95
64.282.4
67.252.44

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F9
0
7.902.01
9.700.42
14.080.35
17.871.02
23.060.86
26.160.36
29.170.56
33.611.01
37.400.86
41.160.65
45.631.22
47.981.3
56.700.56
61.411.1
28

Development and Characterization of Transdermal Patch for Controlled Release of Fluocinolone Acetonide

Fig 1c : Cumulative % Drug Release v/s Time (F1-F9)

Fig 1d : Contour Plot Showing the Effect of X1 and X2 on % Cumulative Drug Release

Design-Expert Software
Factor Coding: Actual
% drug release
Design Points
88.16

% drug release
0.90

70

65

62.3
0.80

X1 = A: Amount of Polyox
X2 = B: amount of PG

B: amount of PG

75
0.70

80

0.60

0.50

85
0.40

0.30
0.10

0.17

0.25

0.33

0.40

A: Amount of Polyox

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29

Design-Expert Software
Factor Coding: Actual
Overlay Plot

Overlay Plot

0.90

% drug release
moisture content
Design Points

0.80

B: amount of PG

X1 = A: Amount of Polyox
X2 = B: amount of PG
0.70

moisture content: 8.000

0.60

moisture content: 12.000

% drug release: 80.000

0.50

% drug release:
moisture conten
X1
X2

0.40

86.970
8.316
0.20
0.30

0.30
0.10

0.17

0.25

0.33

0.40

A: Amount of Polyox

Fig 1e : Contour Plot Showing the Effect of X1 and X2 on % Moisture Content

Design-Expert Software
Factor Coding: Actual
moisture content
Design Points
23.1

moisture content

0.90

4.14
0.80

X1 = A: Amount of Polyox
X2 = B: amount of PG

B : am ount of P G

0.70

10

0.60

15

20

0.50

0.40

0.30
0.10

0.17

0.25

0.33

0.40

A: Amount of Polyox

Fig If : Overlay Plot Shows Optimal Area of Factor Can be Used for Desired Response
CONCLUSION
From the various amount of Polyox and PG,

was found highest among all the batches

batch F2 was found optimum for use further.

which are reasonably desirable for formulation

The patch of F2 batch (Polyox 0.25 gm and

and can be used for controlled release

PG 0.30 gm) also found good in appearance,

formulation.

smoothness, folding endurance and adhesion.

% Cumulative release (at 24 hrs.) of F2 batch
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30

Development and Characterization of Transdermal Patch for Controlled Release of Fluocinolone Acetonide
7. Dr. Reddy. A. In vitro characterization and

ACKNOWLEDGEMENT

evaluation of transdermal drug delivery

Authors

wishes

to

acknowledge

Tripda

Pharmaceuticals, Ahmedabad for providing

gift sample of drug, Fluocinolone acetonide.

system for metoprolol tartarate, JPRHC, 2

(4), 325-329.
8. Keleb, E., & Sharma. R.(2010). Transdermal
Drug

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HOW TO CITE THIS ARTICLE

Joshi, D. M., Patel, S., Moin, M. K., Anandkumar, K. P., Patel, V. M. (2014). Development and
Characterization of Transdermal Patch for Controlled Release of Fluocinolone Acetonide. Journal
Club for Pharmaceutical Sciences, 1(I), 21-32.

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32