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ABSTRACT
The present investigation is concerned with formulation and evaluation of
Transdermal gels of Diclofenac sodium, anti-inflammatory drug, to circumvent the first
pass effect and to improve its bioavailability with reduction in dosing frequency and
dose related side effects. Twelve formulations were developed with varying
concentrations of polymers like Carbopol 934P, HPMCK4M and Sodium CMC. The
gels were tested for clarity, Homogeneity, Spreadability, Extrudability, Viscosity,
surface pH, drug Content uniformity, in-vitro drug diffusion study and ex-vivo
permeation study using rat abdominal skin. FTIR studies showed no evidence on
interactions between drug, polymers and excipients. The best in-vitro drug release
profile was achieved with the formulation F4 containing 1 gm of Diclofenac sodium
exhibited 6 h sustained drug release i.e. 98.68 % with desired therapeutic
concentration which contains the drug and Carbopol 934p in the ratio of 1:2. The
surface pH, drug content and viscosity of the formulation F4 was found to be 6.27,
101.3% and 3,10,000cps respectively. The drug permeation from formulation F4 was
slow and steady and 0.89gm of Diclofenac sodium could permeated through the rat
abdominal skin membrane with a flux of 0.071 gm hr-1 cm-2. The in-vitro release
kinetics studies reveal that all formulations fits well with zero order kinetics followed by
non-Fickian diffusion mechanism.
Key words: Transdermal gel, Viscosity, In-vitro drug release, In-vitro drug release
kinetics study, Ex-vivo permeation study.
INTRODUCTION
selective
corneum
percutaneous absorption[3].
penetration
provides
the
barrier.
greatest
Percutaneous
resistance
to
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248
Preformulation studies:
Description
solid
formulation[4-5].
Melting Point
Diclofenac
sodium
(2-{2-[(2,6
dichlorophenyl)
[7].
condition
classical
Non-steroidal
drug
Procedure:
present
of
study,
anti-inflammatory
formulation
and
evaluation
Materials:
grade.
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Evaluation of Gels
S=M.L/T
Extrudability
Clarity
02].
Surface pH [8]
Homogeneity:
Viscosity[8]
[Table 02].
Viscosity
Consistency
Drug content[8]
Spreadability:
was
determined
by using
brookfield
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250
equation.
Mt/M = ktn
is diffusion exponent.
Tissue Isolation
F=K0t
skin membrane
equation.
Log (100-F) = kt
F=
kt1/2
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[Table 06]
HPLC method.
J = dQ / A dt
Where J is flux (mg
HPLC analysis:
skin.
Preformulation studies
Column: C18, 5m
British Pharmacopoeia.
Temp: 35C
Time -10min
ratio)
Compatibility studies
Clarity:
Stability studies
Homogeneity:
All
developed
gels
(F1-F12)
showed
good
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252
Spreadability:
Drug Content:
was
In-vitro
Extrudability:
Surface pH:
release.
Viscosity Measurement:
in
253
drug
release
study
Jul-Sept 2013
of
different
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gel
skin.
R2
followed
of
Stability Studies:
non-Fickian diffusion.
252C/605%RH
zero-order
kinetics.
But
in
case
for
first
30
days
and
Table 1: Formula for the preparation of Diclofenac sodium Transdermal gels using Carbopol 934P, HPMCK4M and
Sodium CMC
Ingredients
Diclofenac sodium (gm)
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
0.5
1.5
2.5
3.5
Sodium CMC
1.5
2.5
Triethanolamine (ml)
0.4
0.6
0.8
1.0
Alcohol (ml)
20
20
20
20
--
10
10
10
10
30
30
30
30
30
30
30
30
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
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Clarity
Homogeneity
Spreadability
Extrudability
Satisfactory
18.75
++
Good
19.85
++
F3
++
Good
22.55
++
F4
+++
Excellent
27.39
+++
F5
++
Good
20.06
F6
++
Good
21.08
++
F7
++
Good
23.54
++
F8
++
Good
24.27
++
F9
++
Good
19.07
++
F10
+++
Excellent
21.81
+++
F11
++
Good
24.57
++
F12
++
Good
23.25
++
pH
Viscosity (cps)
F1
5.710.05
3,20,000
98.530.21
F2
5.790.15
1,92,000
97.210.18
F3
6.120.02
2,40,000
98.920.27
F4
6.270.03
3,10,000
101.30.22
F5
6.640.02
1,44,000
101.460.26
F6
6.450.07
1,47,000
98.920.25
F7
6.820.05
1,38,000
98.820.31
F8
6.600.04
1,36,000
99.950.18
F9
6.910.02
1,52,000
97.940.33
F10
6.730.09
1,60,000
98.080.40
F11
5.980.12
1,70,000
97.240.38
F12
5.650.14
1,80,000
99.130.19
First order
R2
R2
R2
R2
F1
0.989
0.899
0.996
0.783
0.955
F2
0.990
0.871
0.997
0.780
0.955
F3
0.989
0.870
0.990
0.7765
0.951
F4
0.990
0.932
0.997
0.784
0.953
F5
0.990
0.922
0.993
0.788
0.951
F6
0.990
0.908
0.995
0.789
0.952
F7
0.984
0.969
0.944
0.784
0.927
F8
0.987
0.963
0.972
0.809
0.939
Formulation code
255
Korsmeyer-Peppas
Higuchi
F9
0.989
0.927
0.983
0.787
0.942
F10
0.982
0.977
0.980
0.774
0.952
F11
0.987
0.967
0.972
0.789
0.940
F12
0.985
0.970
0.960
0.793
0.936
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Formulation Days
F4
F4
F4
F4
F4
0
15
30
60
90
Temperature
Drug In-vitro drug
and Relative
Appearance pH
content
release
Humidity
252C/605%RH
Clear
6.27 101.3
98.68
252C/605%RH
Clear
6.25 101.1
98.60
252C/605%RH
Clear
6.20
99.8
98.50
402C/755%RH
Clear
6.18
99.5
98.35
402C/755%RH
Clear
6.15
99.2
98.20
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Fig 5: FTIR Spectra of Diclofenac sodium + Carbopol 934P + HPMCK4M + Sodium CMC
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Fig 10: Comparison of In-vitro drug release profile of formulations F4, F8 and F10
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CONCLUSION
B.,Jack
L.,Semisolids.
In:
Lachmann
L,
pharmacokinetics
and
possibly
permeate
through
human
abdominal
REFERENCES
carboxymethyl
259
Hydroxypropyl
Guar
and
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