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Kamble S.R. , Prachi Udapurkar , Nakhat P.D. , Yeole P.G. and Biyani K.R.
1
Anuradha College of Pharmcy, Anuradha Nagar, Sakegaon Road Chikhli, Buldana-443 201
ABSTRACT
Submitted: 15/4/2010
Revised: 30/6/2010
Accepted: 28/8/2010
The studies were conducted with an object to develop stable safe and efficient delivery system for aceclofenac. During the course of studies
different organogel formulations of aceclofenac for topical application were prepared by using sorbitan monostearate (span 60), isopropyl
myristate, purified water, sorbic acid, potassium sorbate, tween 20, vitamin E, methyl salicylate and menthol. The formulated organogels were
evaluated for psychorheological characteristic, drug content, pH, spreadability. The viscosities of different formulations were determined by
using Brookfield Viscometer at 25C, the viscosity of formulations increases as the surfactant concentration increases. The developed
2
formulation then subjected to in vitro diffusion study. The two formulations showed best release having flux > 0.2 mg/cm /hr were selected and
modified with incorporation of 10% methyl salicylate and 5% menthol. Further efficacy of these formulations was evaluated and compared with
standard marketed formulation by anti-inflammatory activity on albino rats using carageenan-induced rat paw edema model, promissing
edema inhibition withen three hr was observed. Safety was determine through skin irritancy testing on Guinea pigs for seven days showing no
signs of skin irritation. Finally stability studies were carried out for three months showed no separation of gel indicating overall stability. The
result indicates that Sorbitan Monostearate organogels serves as a better vehicle for topical delivery of aceclofenac.
KEYWORDS: Aceclofenac, Sorbiton monostearate, Organogel
INTRODUCTION
Aceclofenac is a phenylacetic acid derivative which has an
established use in inflammation caused by soft tissue injury
and rheumatic diseases including osteoarthritis.1 The main
concern with this drug is that relatively high quantities of drug
must first be systemically administered to treat inflammation
which may be the cause of many adverse effects. Hence in the
present study attempt has been made to improve its
therapeutic performance by developing topical gel
formulation which will improve penetration across skin,
increase availability at desired site and improve patient
compliance with avoidance of undesirable effects. Gels are
intermediate states of matter containing both solid and liquid
components. The solid component comprises a three
dimensional network of interconnected molecule or
Address for Correspondence:
Kamble S.R, Anuradha College of Pharmcy, Anuradha Nagar, Sakegaon Road Chikhli,
Buldana-443 201
E- mail: ksantosh_49@rediffmail.com
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Kamble et al.: Development and Evaluation of Sorbitan Monostearate Organogels as a Topical Delivery System for Aceclofenac
Preperation of Organogel:
Organogels (F1-F7) were formulated by preparing oil phase
and aqueous phase at 60. The composition of oil phase was
sorbitan monostearate (7-13%), sorbic acid (0.2%), tween 20
(2%) and isopropyl merystate while that of aqueous phase
was potassium sorbate (0.2%) in purified water finally
aceclofenac (1.5%) was incorporated in oil phase and
aqueous phase was slowly added to it with stirring. Organogel
(F8 and F9) were formulated by modifying F1 and F2
respectively with incorporation of 10% methyl salicylate and
5% menthol respectively. The composition of different
formulation is summarized in Table No 1.
Evaluation of Organogel:
Psychorheological Characterization:
The formulated gels were inspected visually for colour,
presence of any clog and sudden viscosity changes. To
evaluate the feel, the formulations were applied on the skin
and the feel was experienced psychorheologically. 5
Drug content:
Each formulation (0.5g) was dissolved in 50 ml ethanol. The
solution was filtered through 42 membrane; 1ml of the
above filtrate was pipetted out and diluted to 10ml with
ethanol. The absorbance was measured at 276.5 nm, using
double beam UV visible spectrophotometer (Model: UV2401 PC, Shimadzu Corporation, Singapore).6
pH Determination:
The pH of formulated organogels was determined using pH
meter. The electrode was immersed in organogels and
readings were recorded on pH meter.7
Viscosity:
Contents
F1
F2
F3
F4
F5
F6
F7
Aceclofenac (% wt)
1.5
1.5
1.5
1.5
1.5
1.5
1.5
Span 60 (% wt)
10
11
12
13
Tween 20 (% wt)
0.2
0.2
0.2
0.2
0.2
0.2
0.2
Vitamin E (% wt)
0.1
0.1
0.1
0.1
0.1
0.1
0.1
Isopropyl myristate up to (% wt )
100
100
100
100
100
100
100
0.2
0.2
0.2
0.2
0.2
0.2
0.2
30
30
30
30
30
30
30
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Kamble et al.: Development and Evaluation of Sorbitan Monostearate Organogels as a Topical Delivery System for Aceclofenac
Kamble et al.: Development and Evaluation of Sorbitan Monostearate Organogels as a Topical Delivery System for Aceclofenac
Formulation
Drug
content* (%)
pH
Viscosity
(centipoise)
Spreadability*
(gcm/sec)
F1
F2
F3
F4
F5
F6
F7
F8
F9
99.89 0.41
98.66 0.40
99.61 1.02
100.2 0.43
99.07 0.82
99.61 1.438
98.07 0.40
99.89 0.41
98.66 0.40
5.16
5.25
5.40
5.53
5.30
5.58
5.31
5.11
5.20
27500
30400
33000
36800
38500
42600
47200
27500
30400
52.70 1.03
50.18 1.05
45.56 0.46
43.07 0.79
39.11 0.52
37.23 0.37
32.19 0.20
52.70 1.03
50.18 1.05
In vitro parameters
Flux
Permeability
2
(mg/cm /hr)
coefficient
0.216
0.201
0.201
0.192
0.174
0.164
0.184
0.216
0.201
0.029
0.027
0.028
0.026
0.023
0.022
0.024
0.029
0.027
CONCLUSION
Findings of this study suggest that sorbiton monostearate
based organogels is able to provide desired anti-inflammatory
action. In vitro permeation study demonstrated that organogel
was effective in providing faster drug release. In vivo study
confirmed the findings of in vitro study. The result indicates
that organogel exhibits useful pharmaceutical properties and
serves as a better vehicle for topical delivery of aceclofenac.
Hence, sorbiton monostearate based organogels seems to be a
promising novel topical delivery system for aceclofenac.
However, the role of the formulation developed in this study
can only be settled with clinical investigations on humans
with emphasis on therapeutic index and side effects followed
by pilot scale studies of manufacturing the product for
commercial use.
ACKNOWLEDGMENT
The Authors are grateful to Suyash Laboratories, Mumbai
(India) for gift sample of aceclofenac.
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Kamble et al.: Development and Evaluation of Sorbitan Monostearate Organogels as a Topical Delivery System for Aceclofenac
Kamble et al.: Development and Evaluation of Sorbitan Monostearate Organogels as a Topical Delivery System for Aceclofenac
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