Pharmacology & Pharmacy, 2011, 2, 199-211
doi:10.4236/pp.2011.23029 Published Online July 2011 (http://www.scirp.org/journal/pp)
199
Design, Formulation and Evaluation of
Transdermal Drug Delivery System of Budesonide
Updesh B. Lade*, Yogesh M. Amgaonkar, Rupesh V. Chikhale*, Dinesh M. Biyani, Milind J. Umekar
Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Sadashivrao Patil Shikshan Sanstha, New Kamptee,
Nagpur (M.S), India.
Received January 24th, 2011; revised March 30th, 2011; accepted May 28th, 2011.
ABSTRACT
Budesonide is a highly potent synthetic, nonhalogenated corticosteroid. The mechanism of action of corticosteroids in
allergic rhinitis remains unknown, but may involve reductions in number of various mediator cells such as basophils,
eosinophils, T-helper cells, mast cells, and neutrophils. In the nasal mucosa, nasal reactivity to allergens, and release
of inflammatory mediators and proteolytic enzymes. Budesonide is very effective and quikly acting as it is rapidly and
almost completely absorbed after oral administration, but has poor systemic availability (about 10%) due to extensive
first-pass metabolism in the liver, mainly by the cytochrome P450 isoenzyme CYP3A4. The major metabolites, 6-β-
hydroxybudesonide and 16-α-hydroxyprednisolone have less than 1% of the glucocorticoid activity of unchanged drug
with a terminal half-life of about 2 - 4 hours. Polymeric films containing Eudragit RL 100: Eudragit RS: drug (7:3:1, 7:
2:1) and Ethyl cellulose: PVP: drug (7:3:1, 7:2:1) were selected for transdermal administration based on evaluation
studies. These polymeric films were prepared by mercury substrate method employing PEG-400 as plasticizer. Two
different penetration enhancers Urea and Dimethyl sulphoxide (DMSO) were employed in the study. The patches in
each group were uniform in drug content, thickness. In Vitro drug permeation, moisture absorption and WVTR studies
were carried out on these test patches. It was found that at all humidity condition the absorption increases which were
linear to the moisture absorbed. In PVA and EUDRAGIT RL 100 patches the water vapor transmission rate was found
to be higher at 75% RH, RT conditions. Therefore at both % RH, RT condition the PVA and EUDRAGIT RL 100
patches provide the best resistance to water vapor. Therefore, when applied to animals (in further studies) these
patches may provide more occlusion to water vapor loss from skin thus making atmosphere beneath the skin more hu-
mid that aid in drug permeation.
Keywords: Budesonide, Transdermal Drug Delivery
1. Introduction
Corticosteroids and their biologically active synthetic
derivatives differ in their metabolic (glucocorticoid) and
electrolyte-regulating (mineralocorticoid) activities. These
agents are employed at physiological doses for replace-
ment therapy when endogenous production is impaired.
In addition, glucocorticoids potently suppress inflamma-
tion, and their use in a variety of inflammatory, asthmatic
conditions, skin disorders, rhinitis, inflammatory bowel
disease, collagenous colitis and autoimmune diseases
makes them among the most frequently prescribed
classes of drugs [1]. Budesonide is a highly potent syn-
thetic, nonhalogenated corticosteroid. It has high gluco-
corticoid and weak mineralocorticoid activity [2]. Exact
mechanism(s) of action of corticosteroids in allergic
rhinitis remains unknown, but may involve reductions in
the following: number of mediator cells (basophils,
eosinophils, T-helper cells, mast cells, and neutrophils)
in the nasal mucosa, nasal reactivity to allergens, and
release of inflammatory mediators and proteolytic en-
zymes [3].
Budesonide is rapidly and almost completely absorbed
after oral administration, but has poor systemic availabil-
ity (about 10%) due to extensive first-pass metabolism in
the liver, mainly by the cytochrome P450 isoenzyme
CYP3A4 [4]. The major metabolites, 6-β-hydroxybude-
sonide and 16-α-hydroxyprednisolone have less than 1%
of the glucocorticoid activity of unchanged drug with a
terminal half-life of about 2 - 4 hours [4-6].
The polymeric film containing Eudragit RL 100: Eud-
ragit RS: drug (7:3:1, 7:2:1) and Ethyl cellulose: PVP:

200 Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide
drug (7:3:1, 7:2:1) were selected for transdermal admini-
stration based on evaluation studies [7,8]. The polymeric
films were prepared by mercury substrate method em-
ploying PEG-400 as plasticizer. Two different penetra-
tion enhancers Urea and Dimethyl sulphoxide (DMSO)
were employed in the study. The dried polymeric film
was evaluated using different parameters including thi-
ckness uniformity, drug content of the film, in vitro drug
release from films and in vitro skin permeation of drug,
prior to their in vivo evaluation [8,9].
2. Materials and Methods
2.1. Materials
Budesonide (gift sample from M/s. Cipla Pharmaceuti-
cals Ltd., Mumbai, India), Eudragit RL-100, Eudragit
RS-100 (Röhm GmbH & Co. KG, Pharma Polymers,
Darmstadt, Germany), Polyethylene glycol (PEG-400),
Cellophane Membrane, Polyvinyl alcohol (PVA), Ethyl
cellulose (14 cps), PVP (Mol. Wt. 40,000), Potassium
dihydrogenorthophosphate, Potassium carbonate, Potas-
sium nitrate, Sodium chloride, Sodium hydroxide, Urea,
Dimethyl sulphoxides (DMSO), Glyceryl triacetate, all
other chemicals used were of analytical grade and ob-
tained commercially.
2.2. Animals
The Swiss albino rats (170 - 190 gm) were obtained from
National Chemical Labortary, Pune, India, and main-
tained at 25 ± 1˚C for the study. The animals were
housed in stainless metabolic cages and provided with
standard diet and water ad libitum. Necessary approvals
were obtained from CPCSEA India, for conducting the
study.
2.3. Preparation and Evaluation of Polymeric
Films
2.3.1. Preparation of Transdermal Patch by Solvent
Casting on Mercury Substrate [10,11]
The transdermal patch was prepared by solvent evapora-
tion technique on mercury substrate. Polymer solution
was prepared in ethanol (10 ml) and to it budesonide was
added. The plasticizer or permeation enhancer or the
pore forming agent were added during patch casting. The
solution was poured on glass rings placed on mercury
surface and allowed to dry in air for 24 hours. Circular
patches of 2 cm diameter (3.14 cm2) were cut from semi-
dried patches and placed in desiccator with 0% Relative
Humidity (RH).
2.3.2. Evaluation of patch
1) Measurement of thickness [11]
Thickness was measured using micrometer screw
gauge. Each patch was measured for thickness at five
different points to ascertain thickness uniformity in
patch.
2) Drug content [11]
Accurately weighed patches were individually dissol-
ved in minimum quantity of ethanol and volume was
made up to 20 ml with pH 7.4 phosphate buffer contain-
ing 2.5% ethanol. From this solution, 1 ml was trans-
ferred to volumetric flask and volume was made up to 10
ml. The absorbance was recorded at 247 nm. The blank
solution was prepared in the similar way except that the
patches without drug were used.
3) Moisture absorption studies [12]
The moisture absorption study was carried out at 43,
75, 93% RH, RT at 25 ± 1 °C. The pre-weighed samples
of patches were kept under the humidity conditions and
weighed after 24 hours. The increase in weight indicates
the moisture absorption by samples.
4) Dissolution studies [13,14]
The accurately weighed patches were fixed on glass
discs of 2.5 cm diameter using standard glue. This as-
sembly was kept in dissolution vessel such that the patch
faced the dissolution media upwards. The dissolution
media was 900 ml of pH 7.4 phosphate buffer containing
2.5% ethanol at 32 ± 0.5˚C. The speed of paddle was
kept at 50 rpm. Samples were withdrawn at 1 hour inter-
val till 12 hours and replaced with the media. The ab-
sorbance was measured at 247 nm against the blank.
5) In vitro skin permeation studies [10]
Cellophane membrane was used. The membrane was
mounted between the donor and receptor compartment of
Franz diffusion cell. The patch was kept in contact with
cellophane membrane. The receptor compartment con-
tained pH 7.4 phosphate buffer containing 2.5% ethanol.
The assembly was kept on a magnetic stirrer and stirred
at a speed of 200 rpm. The temperature of assembly was
kept at 37 ± 1˚C. After each hour, 1ml of sample was
withdrawn and replaced with same media up to 24 hours
to study.
6) Effect of drugs loading and polymer concentra-
tion on film [15]
Films with different drug load and polymer concentra-
tion were prepared and studied for their thickness, mois-
ture absorption, and In vitro drug permeation.
7) Effect of penetration enhancers on film
Two penetration enhancers namely urea, dimethylsul-
phoxide (DMSO) were incorporated in different pro-
portion 5 and 10%. The films were then evaluated for the
properties as mentioned earlier.
8) Effect of plasticizers on film
Two plasticizers namely polyethylene glycol-400,
glyceryl triacetate were added in different concentration
5 and 10 % of polymer concentration. These films were
then evaluated for the properties as mentioned earlier.
C opyright © 2011 SciRes. PP

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide 201
Model Equation
Zero order Kinetics Q = Q0 – K0t
First order kinetics Q = Q0 (1 – e –Klt )
Higuchi square root model Qt = KH·t1/2
Hixson-Crowell cube root model 3√Q0 - 3√Qt = KHCt
Korsmeyer-peppas model Qt/Q∞ = Kk·tn
where, Qt—amount of drug released at time t;
Qo—initial amount of drug. and Ko, K1, KH, KHC and
KK are the coefficients of equations.
9) Water vapor transmission rate (WVTR)
The WVTR study was carried out in desiccators
main- tained at 43 and 75% RH at 25 ± 1˚C using satu-
rated solution of potassium carbonate and sodium chlo-
ride respectively. Patches were placed on the mouth of
glass vials containing fused calcium chloride and sealed
using silicon wax. These vials were accurately weighed
and placed in desiccators at 0% RH. The weight of
these vi- als was recorded after 24 hours. The increase
in weight was indicative of water transmission across
the patch.
10) Study of drug release kinetics [16]
In order to investigate the drug release mechanism
from patches, the % cumulative drug release data was
analyzed with following mathematical model.
The most appropriate model was selected on the basis
of goodness of fit test. The zero order kinetic describes
the systems in which the drug release rate is independent
of its concentration. The drug releases slowly (assuming
that the area does not change and no equilibrium condi-
tions are obtained). The first order kinetics describes the
systems in which drug release rate is concentration de-
pendent. Higuchi model describes the release of water-
soluble drug from an insoluble matrix as a diffusion
process based on the Fick’s law and is square root time
dependent.
The Hixson-Crowell cube root law describes the drug
release from a system depends upon the change in sur-
face area or diameter of particle or system and involves
no diffusion mechanism. Korsmeyer-Peppas model de-
scribes the fraction of drug release relates exponentially
with respect to time. This model is generally used to
analyze the release of pharmaceutical polymeric dosage
forms, when the release mechanism is not well known or
when more than one type of release phenomena could be
involved.
11) Skin irritancy study [17,18]
Area on the back of rats was clean shaved 24 hours
prior to testing. Optimize patch was applied to the clean
area and kept in its place by adhesive tape. After every
hour, the patch was removed and observed visually for
signs of edema or erythema and scored according to
Draize’s scoring index. Patch without drug was used as
control patch.
3. Results and Discussion
3.1. Table 1. Effect of Drug Loading and
Polymer Concentration on Film
The patches in each group are uniform in drug distribu-
tion. The thickness and weight increases with the in-
crease in polymer concentration. The films formed are
transparent in appearance. (Tables 1 and 2)
3.2. Table 2. Characterization of Eudragit RL
100 Patches
3.3. Moisture absorption study
The patches were subjected to different % RH, RT con-
ditions and the absorption of moisture noted the results
are shown as under;
3.3.1. Table 3. Moisture Absorption of PVA Patches
Visual examination indicates that, at 43% RH, RT no
change was observed in PVA patches on 7th day, while
at 75% RH, RT the PVA Patches lost there shape on 7th
Table 1. Effect of drug loading and polymer concentration
on film.
PVAEudragit
RL 100
% Polymer
Concentra-
tion Drug Appear-
ance
Thick-
ness
(mm)
Weight
(mg)
Con-
tent
(mg)
P1
P2
P3
P4
U1
U2
U3
U4
5
6
7
8
-
-
-
-
Transparent
---Do----
---Do----
---Do----
0.019
0.020
0.021
0.023
22.1
24.4
29.1
29.5
1.910
1.877
1.891
1.848
V1
V2
V3
V4
Eu1
Eu2
Eu3
Eu4
5
6
7
8
15
15
15
15
---Do----
---Do----
---Do----
---Do----
0.015
0.017
0.019
0.021
18.6
20.2
23.9
26.4
1.040
1.002
1.035
0.988
F1
F2
F3
F4
El1
El2
El3
El4
5
6
7
8
10
10
10
10
---Do----
---Do----
---Do----
---Do----
0.018
0.019
0.021
0.023
16.2
22.1
25.4
29.2
0.137
0.146
0.170
0.212
J1
J2
J3
J4
Eb1
Eb2
Eb3
Eb4
5
6
7
8
5
5
5
5
Transparent
---Do----
---Do----
---Do----
0.019
0.020
0.021
0.023
22.1
24.4
29.1
29.5
1.910
1.877
1.891
1.848
Table 2. Characterization of Eudragit RL 100 patches.
CodeAppearanceThickness Weight
(Mg) Content (Mg)
Eu1
Eu2
Eu3
Eu4
Transparent
---Do----
---Do----
---Do----
0.019
0.021
0.023
0.025
21.8
23.8
26.4
29.7
2.671
2.713
2.652
2.661
El1
El2
El3
El4
---Do----
---Do----
---Do----
---Do----
0.017
0.018
0.019
0.022
24.8
25.6
29.8
32.1
1.271
1.290
1.281
1.267
EB1
EB2
EB3
EB4
---Do----
---Do----
---Do----
---Do----
0.015
0.017
0.020
0.023
19.8
22.4
27.3
28.6
0.165
0.174
0.151
0.156

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide
202
Table 3. Moisture absorption of PVA patches.
43% RH, RT
Pot. Carbonate 75% RH, RT Sod. Chloride 93% RH, RT Pot. nitrate
CODE Wt. of patch
(mg) Moist. Absorp. (mg) % ABS. Wt. of patch (mg) Moist. Absorp. (mg) %ABS Wt. of patch (mg) Moist. Absorp. (mg) % ABS
P1
P2
P3
P4
16.0
18.5
17.9
24.9
1.7
1.5
0.4
1.4
10.62
8.10
2.23
5.62
16.4
17.9
18.0
24.7
2.7
2.9
3.6
3.9
16.46
16.20
20.00
15.78
15.0
17.0
16.0
19.8
5.6
6.1
8.4
9.2
37.33
35.88
52.50
46.46
V1
V2
V3
V4
22.1
24.4
29.1
29.5
10.5
7.14
5.79
7.15
47.51
29.26
19.89
24.23
21.9
24.6
28.2
30.4
13.8
15.8
8.2
11.1
63.01
64.22
29.07
36.51
22.4
25.2
27.4
29.6
17.0
19.0
13.7
15.6
75.89
75.39
50.00
52.70
F1
F2
F3
F4
18.6
20.2
23.9
26.4
11.17
6.29
7.43
8.03
60.05
31.13
31.08
30.41
18.8
19.9
24.2
27.0
6.7
8.75
8.55
10.10
35.63
43.96
35.33
37.40
19.4
20.9
23.6
27.2
7.6
10.6
10.8
14.3
39.17
51.45
45.76
52.57
J1
J2
J3
J4
16.2
22.1
25.4
29.2
4.1
3.5
2.4
2.8
25.3
15.83
9.44
9.65
16.5
21.4
24.3
28.2
4.9
3.9
8.6
7.0
29.69
18.22
35.39
24.82
16.9
22.6
25.9
29.6
5.6
8.6
9.9
9.0
33.13
38.05
38.22
30.40
Table 4. Moisture absorption of Eudragit RL 100 patches.
43% RH, RT
Pot. Carbonate 75% RH, RT Sod. Chloride 93% RH, RT Pot. nitrate
CODE Wt. of
patch (mg) Moist. Absorp. (mg) % ABS.Wt. of patch (mg)Moist. Absorp. (mg) %ABS Wt. of patch (mg) Moist. Absorp. (mg) % ABS
U1
U2
U3
U4
15.9
17.7
18.8
20.1
0.3
2.0
1.5
0.8
1.88
11.29
7.97
3.98
15.3
17.9
18.1
20.7
0.3
1.4
1.3
0.5
1.96
7.82
7.18
2.41
15.6
17.4
18.9
20.4
0.6
2.0
1.2
1.6
3.84
11.49
6.34
7.84
EU1
EU2
EU3
EU4
21.8
23.8
26.4
29.7
0.4
2.9
0.7
1.8
1.83
12.18
2.65
6.06
22.2
23.6
27.1
29.9
1.3
0.5
0.8
2.8
5.85
2.11
2.95
9.36
21.3
23.2
26.8
30.1
1.4
3.3
12.5
0.6
6.57
14.22
9.32
1,99
EL1
EL2
EL3
EL4
24.8
25.6
29.8
32.1
1.2
1.4
0.6
1.6
4.83
5.46
2.01
4.98
24.3
25.1
29.3
31.8
0.8
0.6
1.9
1.3
3.29
2.39
6.48
4.08
21.7
26.1
28.6
32.7
2.5
3.5
2.6
2.8
11.52
13.40
9.09
7.95
EB1
EB2
EB3
EB4
19.8
22.4
27.3
28.6
0.9
1.0
1.4
0.8
4.54
4.46
5.12
2.79
19.6
21.9
27.8
28.3
0.4
0.6
1.1
0.7
2.04
2.73
3.95
2.47
20.1
22.9
27.0
28.9
3.0
1.4
1.5
1.8
14.92
6.11
5.55
6.22
day, however the patches were found to be less stable at
93% RH, RT on 5th day.
3.3.2. Table 4. Moisture Absorption of Eudragit RL
100 Patches
For Eudragit RL100 patches at 43% RH, RT the Patches
lost their shape on 7th day, while at 75% RH, RT the
Patches lost their shape on 5th day and at 93% RH, RT
patch were still more unstable and lost their shape at 4th
day.
Since the absorption pattern is not uniform in both the
cases therefore no conclusion can be drawn regarding the
stability of patch from the above data. At every % RH,
RT condition the Eudragit RL 100 patches absorb less
moisture than PVA patches, but PVA patches were found
to be more stable than the Eudragit RL 100 patches.
3.4. In Vitro Drug Permeation through
Cellophane Membrane
The in-vitro permeation of PVA patches was studied by
using cellophane membrane, results obtained are as
shown under;
3.4.1. Table 5. Drug Permeation from PVA Patches (15
mg)
3.4.2. Table 6. Drug Permeation from PVA Patches (10
mg)
3.4.3. Table 7. Drug Permeation from PVA Patches (5
mg)
3.4.4. Figure 1. Effect of PVA Concentration with
Constant Drug Concentration (15 mg) on Drug
Permeation

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide 203
Table 5. Drug permeation from PVA patches (15 mg).
(%) Percent permeated
Time in (hrs.)
CODE
1 2 3 4 5 6 12 24
V1 4.11 4.98 6.21 7.53 8.85 10.33 11.3912.98
V2 4.39 5.30 6.54 7.79 9.06 10.72 11.9413.48
V3 4.99 6.16 7.48 8.73 10.15 11.58 12.9715.05
V4 4.19 5.14 6.36 7.64 8.98 10.26 11.3712.89
Table 6. Drug permeation from PVA patches (10 mg).
(%) Percent permeated
Time in (hrs.)
CODE
1 2 3 4 5 6 12 24
F1 3.82 5.22 6.27 7.31 8.29 9.26 10.7212.06
F2 4.19 5.61 7.19 8.32 9.54 10.70 12.1413.43
F3 4.79 5.88 7.56 8.94 10.18 11.71 13.1414.86
F4 3.63 5.11 5.93 7.14 8.16 9.36 11.0612.41
Table 7. Drug permeation from PVA patche s (5 mg).
(%) Percent permeated
Time in (hrs.)
CODE
1 2 3 4 5 6 12 24
J1 3.42 4.81 5.83 6.85 7.82 8.77 10.2111.53
J2 3.79 5.20 6.76 7.87 9.07 10.21 11.6312.91
J3 4.40 5.46 7.13 8.49 9.71 11.21 12.6314.32
J4 3.23 4.71 5.48 6.68 8.48 9.84 11.3412.57
Figure 1. Effect of PVA concentration with constant drug
concentration (15 mg) on drug permeation.
3.4.5. Figure 2. Effect of PVA Concentration with
Constant Drug Concentration (10 mg) on Drug
Permeation
3.4.6. Figure 3. Effect of PVA Concentration with
Constant Drug Co ncent r a tion (5 mg) on Drug
Permeation
The in vitro drug permeation in all the cases increase up
to 7% w/w polymer concentration while at 8% it de-
creases with constant drug load, the permeation of drug
increases with increase in polymer content up to 7% w/w
and thereafter it decrease. With constant polymer con-
centration, higher drug load gives higher permeation of
drug. Thus the maximum percent permeation in V, F,
Figure 2. Effect of PVA concentration with constant drug
concentration (10 mg) on drug permeation.
Figure 3. Effect of PVA concentration with constant drug
concentration (5 mg) on drug permeation.
and J series was observed with 7% w/w polymer concen-
tration and it was 15.05%, 14.86%, 14.32% respectively
as represented by Figure 1, 2 and 3 for PVA concentra-
tion.
3.5. In Vitro Drug Permeation through
Cellophane Membrane
The drug permeation through cellophane membrane was
studied, results obtained are as shown under;
3.5.1. Table 8. Drug Permeation from EUDRAGIT RL
100 Patches (15 mg)
3.5.2. Figure 4. Effect of EUDRAGIT RL 100 conc.
with Constant Drug Concentration (15 mg) on
Drug Permeation
3.5.3. Table 9. Drug Permeation from EUDRAGIT RL
100 Patches (10 mg)
3.5.4. Figure 5. Effect of EUDRAGIT RL 100 conc.
with Constant Drug Concentration (10 mg) on
Drug Permeation

204 Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide
Table 8. Drug permeation from EUDRAGIT RL 100
patches (15 mg).
(%) Percent permeated
Time in (hrs)
CODE 1 2 3 4 5 6 12 24
EU1 5.76 6.61 7.83 8.74 10.25 11.49 13.0614.60
EU2 6.23 7.46 8.55 9.85 10.85 12.13 13.4615.44
EU3 5.28 6.54 7.92 8.89 10.48 11.48 13.1514.72
EU4 5.45 6.41 7.54 8.56 9.87 11.11 12.3713.92
Figure 4. Effect of EUDRAGIT RL 100 conc. with constant
drug concentration (15 mg) on drug perm e ation.
Figure 5. Effect of EUDRAGIT RL 100 conc. with constant
drug concentration (10 mg) on drug perm e ation.
Table 9. Drug permeation from EUDRAGIT RL 100
patches (10 mg).
(%) Percent permeated
Time in (hrs)
CODE 1 2 3 4 5 6 12 24
EL1 4.28 5.25 6.44 8.05 9.21 10.68 11.8413.22
EL2 5.21 5.94 6.97 8.56 9.69 11.05 12.315.39
EL3 3.76 5.54 6.56 7.94 9.32 10.67 11.9213.63
EL4 4.09 5.32 6.33 7.65 8.84 10.16 11.5013.06
3.5.5. Table 10. Drug Permeation from EUDRAGIT RL
100 (5 mg)
3.5.6. Figure 6. Effect of EUDRAGIT RL 100 conc.
with Constant Drug Concentration (5 mg) on
Drug Permeation
The in vitro drug permeation in all the cases increase
upto 6% w/w polymer concentration & there after it
decreases. Higher drug load gives higher permeation of
drug. thus the maximum percent permeation in EU2,
EL2, EB2 series was observed with 6% w/w polymer
Table 10. Drug Permeation from EUDRAGIT RL 100 (5
mg).
(%) Percent permeated
Time in (hrs) CODE 1 2 3 4 5 6 12 24
EB13.895.116.017.60 8.74 10.66 11.8213.21
EB24.825.536.548.11 9.22 11.26 13.1515.20
EB33.375.136.137.49 8.86 10.42 11.6613.60
EB43.704.915.907.20 8.37 9.76 11.4212.67
Figure 6. Effect of EUDRAGIT RL 100 conc. with constant
drug concentration (5 mg) on dr ug permeation.
concentration and it was 15.05%, 14.86%, 14.32% res-
pectively after 24 hrs. PVA 7% w/w gives maximum
drug permeation while EUDRAGIT RL 100 at 6% w/w
gives maximum permeation of drug. The maximum %
permeation with PVA was 15.05 while with EUDRAGIT
RL 100 it was 15.44%. For same drug content, the per-
meation through EUDRAGIT RL100 was better and
higher than with PVA. Also with constant polymer con-
centration the drug permeation by EUDRAGIT RL100
was higher than PVA.
Therefore, with EUDRAGIT RL 100 better permea-
tion may be obtained with less polymer requirement in
in-vitro studies, therefore, EUDRAGIT RL 100 was
better polymer than PVA.
3.6. Effect of Penetration Enhancer on Film
The compositions of various films and patches obtained
were examined and characterized for the parameter are
shown as below;
3.6.1. Table 11. Compositions of Patches with Different
Penetration Enhancers.
3.6.2. Table 1 2. Ch aracterization of PVA &
EUDRAGIT RL 100 with Diff erent Penetration
Enhancers
In both the cases the patches formed are uniform with
respect to drug content also with increase in the amount
of penetration enhancer the weight of the patch also
increase linearly .The thickness was also to be uniform
throughout the patch.
C opyright © 2011 SciRes. PP

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide
205
Table 11. Compositions of patches with different penetra-
tion enhancers.
CODE Polymer (mg) Drug (mg) Urea (mg) DMSO (mg)
S1/M1 PVA/Eudragit
RL100 - 700 5 35 --
S2/M2 PVA/Eudragit
RL100 - 700 5 70 --
T1/R1 PVA/Eudragit
RL100 - 700 5 -- 35
T2/R2 PVA/Eudragit
RL100 - 700 5 -- 70
Table 12. Characterization of PVA & EUDRAGIT RL 100
with different penetration enhancers.
CODE AppearanceThickness
(mm) Weight (mg)Drug con- tent (mg)
S1 Transparent 0.018 26.3 0.302
M1 Transparent 0.017 24.3 0.472
S2 Transparent 0.020 29.1 0.453
M2 Transparent 0.018 27.9 0.879
T1 Transparent 0.017 28.2 0.226
R1 Transparent 0.019 26.2 0.335
T2 Transparent 0.019 32.1 0.430
R2 Transparent 0.021 29.4 0.789
Table 13. Moisture Absorption by PVA and EUDRAGIT RL 100 Patches with Different Penetration Enhancers.
43% RH, RT 75% RH, RT 93% RH, RT
CODE Wt. of Patch
(Mg) Moist. Ab- sor. (Mg)% Absorption Wt. of Patch (Mg) Moist. Ab- sor. (Mg)%Absorption Wt. of Patch (Mg) Moist. Ab- sor. (Mg) % Absorption
S1 26.1 4.5 17.24 27.2 11.9 43.75 28.0 15.0 53.57
S2 28.7 6.2 21.60 28.5 14.1 49.47 28.3 16.8 59.36
T1 28.0 3.1 11.07 28.3 7.4 26.14 27.9 11.2 40.14
T2 31.7 7.1 22.39 31.6 11.8 37.34 32.0 14.6 45.62
M1 24.6 2.1 8.53 24.8 3.9 15.72 24.2 4.8 19.83
M2 27.4 3.6 13.13 27.8 5.4 19.42 27.9 6.7 24.01
R1 26.4 1.8 6.8 26.6 2.6 9.77 26.8 3.5 13.05
R2 29.2 2.9 9.93 29.4 3.7 12.58 29.5 5.1 17.22
3.7. Moisture Absorption
3.7.1. Table 13. Moisture Absorption by PVA and
EUDRAGIT RL 100 Patches with Different
Penetration Enhancers
At 43% RH, RT, the moisture absorption by PVA pa-
tches is comparable with patch without the enhancers i.e.
J3. The moisture absorption increases with increase in
enhancer content. DMSO 10% w/w gives greater ab-
sorption than other i.e. 22.39%. It is found that 75% RH,
RT the absorption pattern is higher than at 43% RH, RT.
At 75% RH, RT maximum absorption is shown by urea
10% w/w with 49.47% absorption & at 95% RH, RT
with 59.36%. All humidity condition the absorption in-
creases with increase in enhancer content. As the humid-
ity increases, there increase in moisture absorption and
this increase linear. However, at 43% RH, RT all the
patches retain their shape at the end of 7th day, At 75%
RH, RT the urea patches lose their shape on 7th day,
while DMSO patches a little sticky to touch. At 95% RH,
RT the urea patches lose their shape on 4th day while
DMSO patches still sticky & lose their shape on 6th day.
It is found that around 43% RH, RT, the moisture ab-
sorption by EUDRAGIT RL 100 patches is comparable
with patch without the enhancers i.e. EB3 urea 10% w/w
absorb moisture more than any other. When the condi-
tions were of 75% RH, RT and at 95% RH, RT the ab-
sorption pattern was found to be higher than at 43% RH,
RT At 75% RH, RT maximum absorption is shown by
urea 10% w/w with 19.42% absorption & at 95% RH,
RT with 24.015. Around all the humidity condition the
absorption increases with increase in enhancer content.
As the humidity increases, there increase in moisture
absorption and this increase linear.
At 43% RH, RT all the patches retain their shape at
the end of 7th day, At 75% RH, RT the urea patches lose
their shape on 6th day, while DMSO patches a little
sticky to touch. At 95% RH, RT the urea patches lose
their shape on 3rd day while DMSO patches still sticky
& lose their shape on 6th day.
Therefore amongst the enhancers, the patches of
UREA & DMSO are stable for 7 days under different
humidity condition.
3.8. In Vitro Drug Permeation through
Cellophane Membrane
The patches were then subjected to in vitro drug permea-
tion through cellophane membrane and the results ob-
tained are indicated as below;
3.8.1. Table 14. Drug Permeation from PVA Patches 5
(Mg) with Different Urea Concentration
3.8.2. Figure 7. Effect on Drug Permeation from PVA
Patches 5 (Mg) with Different Urea Concentration
3.8.3. Table 15. Drug Permeation from PVA Patches 5
(Mg) with Different DMSO Concentration
3.8.4. Figure 8. Effect on Drug Permeation from PVA
Patches 5 (Mg) wi th Different DMSO
Concentration
The result obtained is compared with patches without

206 Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide
Table 14. Drug permeation from PVA patches 5 (Mg) with
different urea concentration.
Percent Permeated Time (Hrs) Enhancement
CODE
1 2 3 4 5 6 12 24 Ratio
S1 4.45 5.42 7.50 9.07 11.02 13.71. 15.38 18.09 1.263
S2 6.65 8.29 10.61 13.06 16.08 18.24 21.64 25.92 1.810
Figure 7. Effect on drug permeation from PVA patches 5
(Mg) with different urea concentration.
Table 15. Drug Permeation from PVA Patches 5 (Mg) with
Different DMSO Concentration
Percent Permeated Time (Hrs) Enhancement
CODE
1 2 3 4 5 6 12 24 Ratio
T1 2.35 3.91 5.74 7.93 9.18 11.28 13.73 16.34 1.141
T2 3.19 5.40 7.11 8.99 10.85 13.81 16.29 19.89 1.388
penetration enhancers i.e. J3. Amongst the different pro-
portion of urea used, urea at 10% w/w concentration
gives maximum drug permeation i.e. of 25.92% with the
enhancement ratio of 1.810. DMSO also increases the
permeation at all concentration. it gives 16.34% , 19.89%
of drug permeation for 5% w/w and 10% w/w of DMSO
respectively with the enhancement ratio of 1.141 & 1.388
respectively. Therefore amongst the various penetration
enhancers used in different proportions urea at 10% w/w
concentration gives maximum drug permeation i.e. of
25.92% with the enhancement ratio of 1.810. Therefore
for budesonide in PVA matrix urea 10% w/w is the best
Figure 8. Effect on drug permeation from PVA patches 5
(Mg) with different DMSO concentration.
penetration enhancer.
3.8.5. Table 16. Drug Permeation from EUDRAGIT RL
100 Patches 5 (Mg) with Different Urea
Concentration
3.8.6. Figure 9. Effect of Different Urea Concentration
on Drug Permeation from EUDRAGIT RL 100
Patches 5 (Mg)
3.8.7. Table 17. Drug Permeation from EUDRAGIT RL
100 Patches 5 (Mg) with Different DMSO
Concentration
3.8.8. Figure 10. Effect of Different DMSO
Concentration on Drug Permeation from
EUDRAGIT RL 100 Patches 5 (M g)
The result obtained is compared with patches without
penetration enhancers i.e. EB3. Amongst the different
proportion of urea used, urea at 10% w/w concentration
gives maximum drug permeation i.e. of 27.38 % with the
enhancement ratio of 2.01. DMSO also increases the
permeation at all concentration. It gives 18.53%, &
24.10% of drug permeation for 5% w/w and 10% w/w of
DMSO respectively with the enhancement ratio of 1.362
& 1.772 respectively. Therefore amongst the various
Table 16. Drug permeation from EUDRAGIT RL 100
patches 5 (Mg) with different urea concentration.
Percent Permeated Time (Hrs) Enhancement
CODE
123456 12 24 Ratio
M14.926.949.4211.22 13.51 15.93 18.07 20.65 1.515
M25.436.969.5912.33 14.90 17.76 21.90 27.38 2.013
C opyright © 2011 SciRes. PP

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide 207
Figure 9. Effect of different urea concentration on drug
permeation from EUDRAGIT RL 100 patches 5 (Mg).
Table 17. Drug permeation from EUDRAGIT RL 100
patches 5 (Mg) with different DMSO concentration.
Percent Permeated Time (Hrs) Enhancement
CODE
1 2 3 4 5 612 24 Ratio
R1 4.22 5.87 7.84 9.75 11.22 13.68 15.44 18.53 1.362
R2 5.01 6.90 9.00 12.04 15.59 17.64 20.61 24.10 1.772
Figure 10. Effect of different DMSO concentration on drug
permeation from EUDRAGIT RL 100 patches 5 (Mg).
penetration enhancers used in different proportions urea
at 10% w/w concentration gives maximum drug permea-
tion i.e. of 27.38% with the enhancement ratio of 2.01.
Therefore for budesonide in EUDRAGIT RL 1OO ma-
trix urea 10% w/w is the best penetration enhancer. For
both PVA & EUDRAGIT RL 100 patches urea is the
best penetration enhancers than DMSO.
3.9. Effect of Plasticizers on Films
The compositions of various films are shown as follows;
3.9.1. Table 18. Compositions of Patches with
Different Plasticizers
The patches obtained were examined and characterized
for the parameter as shown below
3.9.2. Table 19. Characterizati on of P VA & Eudragit
RL 100 Patches with Different Plasticizers
In both the cases the patches formed are uniform with
respect to drug content also with increase in the amount
of plasticizers the weight of the patch also increase line-
arly. The thickness was also to be uniform throughout
the patch.
3.10. Moisture Absorption
3.10.1. Table 20 . Moi sture Absorption Study of PVA
and EUDRAGIT RL 100 Pa tches with
Different Plasticizers
At 43% RH, RT, the moisture absorption by PVA pa-
tches is comparable with patch without the enhancers i.e.
J3. The moisture absorption increases with increase in
plasticizer content. PEG-400 10% w/w gives greater ab-
sorption than other i.e. 59.87%. Around 75% RH, RT the
absorption pattern is higher than at 43% RH, RT. At 75%
RH, RT maximum absorption is shown by PEG-400 10%
w/w with 50.75% absorption & at 95% RH, RT with
59.87%. In all humidity condition the absorption in-
creases with increase in plasticizer content. As the hu-
Table 18. Compositions of patches with different plasticize-
ers.
CODEPolymer - mg Drug
(mg) PEG 400 (mg) Glyceryl triace- tate (mg)
PE1/SO1 PVA/Eudragit RL
100 - 700 5 35 --
PE2/SO2 PVA/Eudragit RL
100 - 700 5 70 --
GL1/LO1 PVA/Eudragit RL
100 - 700 5 -- 35
GL2/LO2 PVA/Eudragit RL
100 - 700 5 -- 70
Table 19. Characterization of PVA & Eudragit RL 100
patches with different plasticizers.
CODEAppearance Thickness
(mm) Weight (mg) Drug content (mg)
PE1Slightly hazy 0.020 28.5 0.302
PE2Slightly hazy 0.024 31.9 0.472
GL1 Very Slightly
sticky 0.021 31.0 0.453
GL2 Very Slightly
sticky 0.026 34.60 0.879
SO1Transparent 0.018 26.5 0.226
SO2Transparent 0.020 29.2 0.335
LO1Transparent 0.019 28.1 0.430
LO2Transparent 0.022 30.3 0.789

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide
208
Table 20. Moisture absorption study of PVA and EUDRAGIT RL 100 patches with different plasticizers.
43% RH, RT 75% RH, RT 93% RH, RT
CODE Wt. of Patch
(mg) Moist. Absorb. (mg) % absorp- tion Wt. o f Patch (mg) Moist. Absorb. (mg) % absorp- tion Wt. of Patch (mg) Moist. Absorb. (mg) % absorp- tion
PE1 28.7 5.1 17.77 28.9 12.8 44.29 28.5 15.4 54.03
PE2 32.4 7.4 22.83 33.1 16.8 50.75 32.9 19.7 59.87
GL1 31.4 4.1 13.05 30.8 8.2 26.62 30.9 13.2 42.71
GL2 34.6 7.2 20.80 34.3 13.5 39.35 34.1 17.2 50.43
SO1 26.2 2.2 8.39 26.7 3.4 12.37 26.5 6.9 26.03
SO2 29.8 3.5 11.74 29.1 6.8 23.36 29.7 9.7 32.65
LO1 28.4 3.5 12.32 29.1 6.9 23.71 28.6 10.8 37.76
LO2 30.2 4.8 15.89 29.8 7.6 25.50 30.6 11.2 36.60
midity increases, there increase in moisture absorption
and this increase linear.
At 43% RH, RT all the patches retain their shape at the
end of 7th day, At 75% RH, RT the PEG-400 patches
lose their shape on 7th day, while glyceryl triacetate
patches a little sticky to touch. At 95% RH, RT the PEG-
400 patches lose their shape on 5th day while glyceryl
triacetate patches still sticky & lose their shape on 6th
day. At 43% RH, RT, the moisture absorption by
EUDRAGIT RL 100 patches is comparable with patch
without the enhancers i.e. EB3. Glyceryl triacetate 10%
w/w absorbs moisture more than any other. At 75% RH,
RT and at 95% RH, RT the absorption pattern is higher
than at 43% RH, RT At 75% RH, RT maximum absorp-
tion is shown by glyceryl triacetate 10% w/w with
25.50% absorption & at 95% RH, RT with 36.60%. At
all humidity condition the absorption increases with in-
crease in enhancer content. As the humidity increases,
there increase in moisture absorption and this increase
linear. At 43% RH, RT all the PEG-400 patches retain
their shape at the end of 7th day, while glyceryl triacetate
patches lost their shape on 6th day. At 75% RH, RT the
PEG-400 patches lose their shape on 6th day, while glyc-
eryl triacetate patches lost their shape on 5th day. At
95% RH, RT the PEG-400 patches lose their shape on
4th day while glyceryl triacetate patches still sticky &
lose their shape on 3rd day. Therefore amongst the plas-
ticizers, the patches of PEG-400 & glyceryl triacetate are
stable for 7 days under different humidity condition, and
selected for final formulation of EUDRAGIT RL 100 &
PVA respectively.
3.11. In Vitro Drug Permeation
3.11.1. Table 21. Drug Permeation from PVA Patches
with Different PEG-400 and Glyceryl Triacetate
Concentration
3.11.2. Table 22. Drug Permeation from Eudragit RL
100 Patches with Different PEG-400 and Glyc-
eryl Triacetate Concentration
3.11.3. Figure 11. Effect of Different Conc. of PEG-400
on Drug Permeation from PVA Matrix
3.11.4. Figure 12. Effect of Different Conc. of Glyceryl
Triacetate on Drug Permeation from PVA Matrix
3.11.5. Figure 13. Effect of Different Conc. of PEG-400
on Drug Permeation from EUDRAGIT RL 100
Matrix
3.11.6. Figure 14. Effect of Different Conc. of
Glyceryl Triacetate on Drug Permeation from
EUDRAGIT RL 100 Matrix
The results are compared with patches without plasticiz-
ers i.e. J3. The PVA patches with 5% & 10% w/w of
PEG-400, the permeation increased from 16.50% to
19.96%. Similarly with glyceryl triacetate the permeation
increased from 17.56% to 23.76 % respectively thus the
glyceryl triacetate with 10% gives maximum permeation
hence it is selected for final formulation.
The results are compared with patches without plasti-
cizers i.e. EB3. The EUDRAGIT RL 100 patches with
Table 21. Drug permeation from PVA patches with differ-
ent PEG-400 and Glyceryl triacetate conce nt r ation.
Percent permeated
Time in (hrs.)
CODE
1 2 3 4 5 6 12 24
PE1 2.394.525.968.20 9.75 11.21 13.8116.50
PE2 3.145.126.829.15 11.30 14.38 17.0719.96
GL1 3.284.946.918.87 10.49 12.64 14.7817.56
GL2 5.017.139.0211.26 13.78 16.40 19.7823.76
Table 22. Drug permeation from Eudragit RL 100 patches
with different PEG-400 and Glyceryl triacetate concentra-
tion.
Percent permeated
Time in (hrs.)
CODE
1 2 3 4 5 6 12 24
SO1 4.226.068.4610.68 12.71 15.05 17.5320.94
SO2 5.016.298.7911.07 13.72 16.39 20.1924.33
LO1 4.175.647.839.41 11.38 13.89 16.6519.42
LO2 4.826.569.0710.99 13.46 16.30 18.9722.54

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide 209
Figure 11. Effect of different Conc. of PEG-400 on drug
permeation from PVA matrix.
Figure 12. Effect of different Conc. of Glyceryl Triacetate
on drug permeation from PVA matrix.
Figure 13. Effect of different Conc. of PEG-400 on drug
permeation from EUDRAGIT RL 100 matrix.
5% & 10% w/w of PEG-400, the permeation increased
from 20.94% to 24.33% .Similarly with glyceryl triaceta-
te the permeation increased from 19.42% to 22.54% resp.
thus the PEG-400 with 10% gives maximum permeation
Figure 14. Effect of different Conc. of GLYCERYL TRI-
ACETATE on drug permeation from EUDRAGIT RL 100
Matrix.
hence it is selected for final formulation.
3.12. Final Preparation
3.12.1. Preparation and Evaluation of Patch Using
Optimum Concentration
Composition of various film prepared is shown in Table
23.
3.12.1.1. Table 23. Composition of Films of PVA and
EUDRAGIT RL 100
The patch obtained was studied and their characterization
was done and is listed in following Table 24.
3.12.1.2. Table 24. Characterization of PVA and
EUDRAGIT RL 100 Patch
The patch in each group is uniform in drug content and
thickness through the patch. And further In Vitro drug
permeation, moisture absorption and WVTR studies
were carried out.
3.12.2. Moisture Absorption: Table 25. Moisture
Absorption Study of Final PVA and
EUDRAGIT RL 100
Table 23. Composition of films of PVA and EUDRAGIT
RL 100.
CODEPOLYMER (mg)DRUG
(Mg) PLASTISIZER (Mg) ENHANCER (Mg)
FP-1PVA-700 5 GLY.TRI-70 UREA-70
FE-1 EUDRAGIT RL
100 - 700 5 PEG400- 70 UREA-70
Table 24. Characterization of PVA and EUDRAGIT
RL 100 patch.
CODEAPPEARANCETHICKNESS WEIGHT
(Mg) DRUG CON- TENT (Mg)
FP-1Transparent 0.019 33.4 1.971
FE-1Transparent 0.018 31.6 2.174

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide
210
Table 25. Moisture absorption study of final PVA and EUDRAGIT RL 100.
43% RH, RT 75% RH, RT 93% RH, RT
CODE Wt. of Patch
(mg) Moist. Absorb. (mg) % absorp- tion Wt. o f Patch (mg) Moist. Absorb. (mg) % absorp- tion Wt. of Patch (mg) Moist. Absorb. (mg) % absorp- tion
FP-1 34.4 9.8 28.48 34.9 17.9 51.28 34.1 21.3 62.46
FE-1 31.9 6.7 21.01 31.7 12.8 40.37 32.1 15.9 49.53
Table 26. WVTR of PVA and Eudragit RL-100 patches.
43% RH, RT 75% RH, RT
CODE Wt. of Patch (mg) Moist. Absorb. (mg) % absor ptionWt. of Patch (mg) M oi st. Absorb. (mg) % absorption
FP-1 0.0021 0.020 0.217 0.0151 0.022 0.882
FE-1 0.0391 0.017 12.76 0.145 0.018 18.86
Table 28. In-Vivo drug permeation from EUDRAGIT RL
100 patches.
3.12.3. Water Vapor Transmi ssi on Ra te Study
(WVTR): Table 26. WVTR of PVA and
Eudragit RL-100 Patches
Percent permeated
Time ( hrs)
CODE
1 2 3 4 5 6 12 24
FE-110.9414.25 17.60 20.85 24.26 27.71 32.07 37.25
At all humidity condition the absorption increases. As At
all humidity condition the absorption increases. As the
humidity increases, there is a increase in moisture ab-
sorption and this increases linearly. The patch FP-1 gives
maximum absorption at 93% RH, RT i.e. 62.46 than any
other. At 43% RH, RT the PVA patches retain their
shape at the end of 7th day, At 75% RH, RT the PVA
patches lose their shape on 7th day, At 95% RH, RT the
PVA patches lose their shape on 5th day.
3.12.4. Drug Permeation through Cellophane
Membrane
3.12.4.1. Table 27. In-Vitro Drug Permeation from
EUDRAGIT RL 100 Patches
3.12.4.2. Table 28. In-Vivo Drug Permeation from
EUDRAGIT RL 100 Patches
3.12.4.3. Figure 15. Drug Permeation of Patch FP-1
3.12.4.4. Figure16. Drug Permeation of Patch Fe-1
At all humidity condition the absorption increases. As
the humidity increases, there increase in moisture ab-
sorption and this increase linearly. The patch FE-1 gives
maximum absorption at 93% RH, RT i.e. 49.53% than
any other. At 43% RH, RT the EUDRAGIT RL 100
Figure 15. Drug Permeation of Patch FP-1.
Table 27. In-Vitro drug permeation from EUDRAGIT RL
100 patches.
Percent permeated
Time ( hrs)
CODE
1 2 3 4 5 6 12 24
FE-1 10.94 14.25 17.60 20.85 24.26 27.71 32.07 37.25
Figure 16. Drug Permeation of Patch Fe-1.

Design, Formulation and Evaluation of Transdermal Drug Delivery System of Budesonide 211
patches lost their shape at the end of 7th day, At 75% RH,
RT the EUDRAGIT RL 100 patches lose their shape on
6th day, At 95% RH, RT the EUDRAGIT RL 100
patches lose their shape on 4th day. In PVA and
EUDRAGIT RL 100 patches the water vapor transmis-
sion rate was found to be higher at 75% RH, RT condi-
tions. Therefore at both % RH, RT condition the PVA
and EUDRAGIT RL 100 patches provides the best resis-
tance to water vapor. Therefore, when applied to animals
(in further studies) these patches may provide more oc-
clusion to water vapor loss from skin thus making at-
mosphere beneath the skin more humid that aid in drug
permeation.
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