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Transcript
155
FORMULATION AND EVALUATION OF MELOXICAM GELS
FOR TOPICAL ADMINISTRATION
Nagia A. El-Megrab, Hanan M. El-Nahas* and Gehan F.Balata
‫تم في هذه الدراسة تحضير عقار ميلوكسيكام في شكل مستححلاا قييقتة هيميتة مهيميتا قهتيتة تححتوم علتا متاق ا يتل‬
‫( مهيميتا كحوليتة تححتوم علتا‬hydrogel) ‫ مكذلك تم تحضير هيميتا ماييتة‬.)‫أمليا أم حامض أمليك (الوسط الدهتي‬
‫ تم قراسة معدل انطيق العقتار متن لتيل ء تا‬.(topical) ‫ كماق إهيمية السحخدامها عن طر ق الجلد‬940 ‫ماق كربوبول‬
%1‫ ) التذم ححتوم علتتا‬7.4 ‫ستيلوفا مكتذلك نذات حتة متن لتيل أللتد ايرنتل فتي محلتول سونستن الكتابج (أ هيتدرمأليتي‬
‫) علا لصتاي‬%1 ، 0.65 ، 0.5( ‫ ميد تم قراسة تأثير تركيز الدما الماديي‬.‫حجم من ماق كار حا لور ل صوق وم‬/ ‫مز‬
‫نذات ة ماق ميلوكسيكام من مسححلاا ماق إ يل أمليا هي أحسن صيغة تم الحصول عليها مقارنتة بتالهيم الحجتارم لعقتار‬
‫ أألر ت قراسة لماق ميلوكسيكام كعقار مضاق ليلحهابا بعد تتامله عن طر تق الذتم مالجلتد للذنترا ممقارنحته‬. ‫بيرمكسيكام‬
‫ أم تحت هتتذه الدراستة أ أعلتتا معتدل معملتتي نطتتيق التدما مامحصاصتته متن لتتيل الجلتد كتتا متتن‬.‫بهتيم بيرمكستتيكام‬
‫ أم تتحت الدراستتة الحتتي أألر تتت علتتا الذنتترا أ هتتيم متتاق‬. ‫المستتححلل التتدييق الهيمتتي المححتتوم علتتا ا يتتل أمليتتا‬
‫ من ماق ا يل أمليا ) أعطا حما ة كايتر تد االلحهتاق مقارنتة‬%1 ‫ميلوكسيكام (المسححلل الدييق الهيمي المححوم علا‬
.(feldene®) ‫بهيم ماق بيرمكسيكام‬
For topical administration of meloxicam (ME), microemulsion gels and lipogels containing either
ethyl oleate or oleic acid as an oil phase were prepared. In addition, Hydrogel and hydroalcoholic
gels containing carbopol 940 as a gelling agent were also prepared. In-vitro drug release through
cellophane membrane and permeation through the excised rabbit skin in Sörensen`s phosphate
buffer (pH 7.4) containing 1% w/v sodium lauryl sulphate were performed .The influence of
initial drug concentration (0.5, 0.65, 1% w/w) was studied. The permeation properties of ME from
ethyl oleate microemulsion which is the best formula achieved was studied in comparison to the
commercially available piroxicam gel. Moreover, the anti-inflammatory activity of ME after oral
and topical administration in rats was studied and compared to that of piroxicam gel. The results
of an in-vitro drug release and its percutaneous permeation revealed that the ethyloleate
microemulsion gel showed the highest results. Meloxicam gel (ethyl oleate microemulsion gel
1%) showed good protection against inflammation as compared to Feldene® gel in rats.
Key words: Meloxicam, lipogels, hydrogels, microemulsion gels, carrageenan.
Introduction
Meloxicam, a non-steroidal anti-inflammatory
drug (NSAID), is a preferential inhibitor of cyclooxygenase-2 and has demonstrated potent analgesic
Department of Pharmaceutics. Faculty of Pharmacy . University
of Zagazig. Zagazig, Egypt.
*
To whom correspondence should be addressed.
E. mail: [email protected]
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
and anti-inflammatory activity after oral administration (1). NSAIDs have been widely used in the
treatment of rheumatoid arthritis and other related
conditions. However, they carry the risk of undesirable systemic side effects and gastrointestinal
irritation at the usual dose of oral administration (2).
Considering the fact that most inflammatory
diseases occur locally and near the surface of the
body, topical application of NSAIDs on the inflamed
site can offer the advantage of delivering a drug
156
EL-MEGRAB ET AL
directly to the disease site and producing its local
effect. This occurs by avoiding gastric irritation and
also reduces adverse systemic effects (3, 4).
However, the barrier properties of intact skin limit
the permeability of wide variety of substances,
including pharmaceutical active agents.
To overcome these problems, the development of
an optimal vehicle system for rapid skin permeation
of ME is required. Currently, microemulsions have
been recognized as good vehicles for percutaneous
absorption of drugs (5, 6). They are clear or slightly
opalescent, isotropic; thermodynamically stable
systems of two immiscible liquids. Microemulsions
are created by the presence of a suitable surfactant,
usually in conjunction with a co-surfactant. They are
relatively stable and can solubilize a considerable
amount of hydrophobic drugs in their lipophilic
domain (7).
Recently, lipogels-semisolid ointment like preparations have been investigated as vehicles for
topical drug delivery. Lipogels are obtained by
gelling an oleaginous phase with a lipophilic
substance (8-10).
The purpose of this study was to formulate ME
in different types of gels, namely, hydrogel,
hydroalcoholic gel, microemulsion gel and lipogel
using different oils. The second goal was to evaluate
the properties of ME gels like in-vitro drug release,
percutaneous absorption and comparison antiinflammatory effect of this gel with the marketed
piroxicam gel.
Experimental
Materials:
Meloxicam powder was donated as a gift from
Delta Pharma, Tenth of Ramadan City, Egypt),
Mexicam® tablets were purchased from Delta
Pharma, Tenth of Ramadan City, Egypt), Feldene®
gel was purchased from (Pfizer Pharm.Co., Cairo,
Egypt), Carbopol 940 was purchased from (BF
Goodrich Co., OH), Ethyl oleate (EO) was
purchased from (Aldrich Chemical, Milwaukee,WI),
Oleic acid was purchased from (Fluka, Buchs, CH),
Glyceryl monostearate
(Henkel,
Düsseldorf,
Germany), Propylene glycol (PG) was purchased
from (Carl Roth, W, Germany), Tween 80
(Polyoxyethylene Sorbitan Monooleate) , Sodium
Lauryl sulphate, Potassium dihydrogenorthophosphate, disodiumhydrogen phosphate, sodium
chloride and ethanol were purchased from (ElSaudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
Nasser Pharmaceutical Chemicals, Cairo, Egypt),
Triethanolamine was purchased from (Merck,
Darmstadt, Germany), Carrageenan and hydroxyl
propylmethylcellulose (HPMC) were purchased
from (Sigma, St, Louis, MO),all chemicals were
analytical grade. Semipermeable Cellophane
membrane 30/32 (Fischer Scientific Co., London,
England). Distilled water, was used in the experiments.
Methods:
Preparation of hydrogel and hydroalcoholic gel
samples:
The gel samples were prepared by dispersing 1%
Carbopol 940 in a mixture of water and PG (80: 20
w/w) in case of hydrogel or a mixture of water,
ethanol and PG ( 40: 40: 20 w/w) in case of
hydroalcoholic gel. ME (1% w/w) was added to the
mixtures and kept under magnetic stirring for 12 hrs
(Formulas 1 and 2, Table 1). The dispersions were
then neutralized (pH 7.4) and their viscosity was
improved by adding triethanolamine 0.01% (11).
Preparation of microemulsion gel samples:
The appropriate amounts of Tween 80, PG and
oil (EO or oleic acid) were weighed into screwcapped vial as surfactant, co-surfactant, and oil
(50:10:40) respectively. ME was added in a
concentration of 1% w/w into the vial. The mixture
was shaken by using a magnetic stirrer (1 cm), then
the microemulsion gel was formed by the addition of
25 % water with continuous stirring, and it was
enhanced by using a vortex mixer for 2 min. The gel
of ME samples were stored at 25°C for 24 hrs for
equilibration (Formula 3, Table 1).
Preparation of lipogel samples:
The calculated amount (15% w/w) of
monoglyceryl stearate was heated at 70 °C with oil
(EO or oleic acid) to complete melting, then 1% ME
was dissolved into the melted mass (formula 4 table
1). The mass was then gelled by cooling under
stirring (100 rpm) to 50°C until clouding of the
melted mass, then allowing to gel at rest. The sample
was then maintained at 25 °C for 24 hrs before use
(10).
Effect of initial drug concentration:
Further study was done upon ethyl oleate
microemulsion gel as it gave the best results of drug
release and skin permeation. The effect of initial ME
FORMULATION AND EVALUATION OF MELOXICAM GELS
concentration was tested on the permeation
properties of that gel by using other two drug
concentrations 0.5 and 0.65% besides 1% ME.
Solubility measurements:
The solubility of ME in either EO or oleic acid
was determined by adding excess amount of drug
into 10 ml of oil in a screw-capped vial. The vials
were equilibrated at 25°C for 72 hrs in a thermostatic
shaker water bath. The suspension was centrifuged
at 3000 rpm for 15 min, and the supernatant was
diluted with ethanol and used for the determination
of ME spectrophotometrically at λmax = 362 nm, the
blank was EO or oleic acid in ethanol.
Viscosity measurements:
The different formulations were tested at room
temperature using Viscostar viscometer (Fungilab
S.A., Spain). The measurements were made using
spindle number 5 at 2 rpm.
In-Vitro drug release:
A one gram sample of each formulation was
accurately weighed and placed on a semipermeable
cellophane membrane (previously immersed in
sörencen`s phosphate buffer, pH 7.4 for 20 hrs) to
occupy a circle of 2.9 cm diameter. The loaded
membrane was stretched over the lower open end of
a glass tube of 2.9 cm diameter and made water tight
by rubber band. The tube was immersed in a beaker
containing 150 ml of Sörencen’s phosphate buffer
pH 7.4. Sodium lauryl sulphate 1% w/w was added
to the medium to ensure sink condition. The system
was maintained for 4 hrs at 32°C in a thermostatic
shaker water bath at 100 rpm (Figure1). Samples 3
ml were withdrawn at intervals of 15, 30, 45, 60, 90,
120, 180, and 240 min, the volume of each sample
was replaced by the same volume of fresh buffer to
maintain constant volume, samples were analyzed
without dilution or filtration
for ME content
spectrophotometrically at λmax = 362 nm. In case of
Feldene® gel, samples were analyzed for piroxicam
content at λmax = 358 nm.
In-Vitro permeation studies:
In-vitro permeation studies with excised rabbit
skin (13) were performed as follows: Abdominal
full-thickness skin of male rabbit was obtained from
white New Zealand rabbits weighing 3-4 kg. The
skin was carefully removed from animals and the
hair was clipped without damaging the skin. The fat
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
157
was removed with the aid of scissor and skin was
washed and soaked over night in 0.9 % sodium
chloride solution. The excised skin was used as a
permeation membrane with the epidermal surface
upward, the stratum corneum was facing the donor
side of the cell and the dermal side of the skin was
allowed to be in contact with a buffer solution
(Figure 1). The procedure for the release test
described above was used except that the receptor
medium contained 150 ml 0.9% sodium chloride of
pH 7.4 with the addition of sodium lauryl sulphate
(1% w/v). Samples of 3 ml were withdrawn
periodically for 9 hrs and replaced with an equal
volume of fresh receptor solution. ME and
piroxicam were assayed spectrophotometrically at
362 nm and 358nm, respectively.
Calculation of cumulative drug release:
The amount of ME in the total receptor solution
was determined from a calibration curve. The
cumulative drug permeated (Qn) corresponding to
the time of the nth sample was calculated from the
following equation (14):
n-1
Qn = VRCn + Σ VsCi
i=0
Where Cn and Ci are the drug concentrations of
the receptor solution at the time of the nth sample
and the i ( the first) sample, respectively and VR and
VS are the volumes of the receptor solution and the
sample, respectively.
Calculation of permeation parameters:
The permeation profiles of ME across rabbit skin
from different gel formulations were constructed by
plotting the total cumulative amount of ME
penetrated per unit surface area (μg/cm2) versus
time (hour) as shown in figure 4. Meloxicam steady
state flux (Jss) was calculated as the slope of linear
regression line at the steady state phase for each
experimental run. Permeability coefficient (Kp) was
calculated using the relation derived from Fick’s first
law of diffusion, which described in the following
equation:
Jss = Kp /Co
where, Co is the initial drug concentration in the
donor (15).
158
EL-MEGRAB ET AL
Anti-inflammatory activity of Meloxicam gel:
Acute inflammatory activity model, carrageenan
induced rat paw edema method (16) was applied in
this study.
The rats weighing about 200 gm were divided
into 6 groups, each group containing 4 rats. The
animals of groups 1, 2 and 3 received 1ml oral
suspension of meloxicam (0.2 mg/kg) in 0.9 %
sodium chloride (17), 200 mg of EO microemulsion
gel topically and 200 mg of feldene® gel topically,
respectively. The gels were applied to the surface of
the right hind paw, then the treated area was
immediately covered by thin vinyl sheet and gauze.
Two hours later, the covers were removed and 0.1
ml of 1% carrageenan solution was injected
subcutaneously into both treated area and the left
hind paw. The animals of control groups 4,5 and 6
were treated with sodium chloride solution orally,
microemulsion placebo gel topically and HPMC
placebo gel topically respectively. The carrageenan
was injected in the same manner as above. Three
hours later, the thickness of the right and left paws
was measured using a dial micrometer and the
percentage inhibition of edema was calculated (18).
The data were reported as mean ± SEM (n=4) and
statistical analysis was carried out using ANOVAtest at a level of significance of P< 0.05.
Results and Discussion
In-Vitro Drug Release and Permeation Studies
Effect of gel type:
The data obtained from release and permeation
studies were shown in Figures 2-5 and Table 2. The
amount of ME released from all gel formulations
show a linear relationship with the square root of
time (r >0.9), therefore, the release rate of the test
drug followed Higuchi theoretical model (19).
It was observed that the in-vitro release data as
well as the permeation studies were superior from
EO microemulsion gel. The cumulative amounts
permeated at 9 hrs were 616.1, 295.15, 141.5 and
235.2 μg/cm2 for EO microemulsion gel, EO lipogel,
carpobol gel and hydroalcoholic carpobol gel
respectively. These results were in agreement with
El-Laithy and El-Shaboury, Who reported that
maximum fluconazole permeation and 1.5 fold
improvement in drug release were achieved from
microemulsion prepared with jojoba oil in
comparison to its corresponding lipogel (20).
Thacharodi and Panduranga (7) explained the
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
mechanism by which microemulsions enhance the
percutaneous absorption of drugs on the basis of the
combined effect of both the lipophilic and
hydrophlilic domains of microemulsion. The lipophilic domain of the microemulsion can interact with
the stratum corneum in many ways. The drug
dissolved in the lipid domain of a microemulsion can
directly partition into the lipid of the stratum
corneum or lipid vesicles themselves can intercalate
between the lipid chains of stratum corneum, thereby
destabilizing its bilayer structure. These interactions
will lead to increased permeability of the lipid
pathway to the drugs. On the other hand, the
hydrophilic domain of the microemulsion can
hydrate the stratum corneum to a greater extent.
When the aqueous fluid of the microemulsion enters
the polar pathway, it will increase inter lamellar
volume of stratum corneum lipid bilayer, resulting in
the disruption of its interfacial structure. Since, some
lipid chains are covalently attached to corneocytes,
hydration of these proteins will also lead to the
disorder of lipid bilayers. Similarly, swelling of the
intercellular proteins may also disturb the lipid
bilayers; a lipophilic penetrant like ME can then
permeate more easily through the lipid pathway of
stratum corneum.
It was observed that the type of oil affect the
release and permeation properties of ME from
microemulsion gels and lipogels. The cumulative
amounts of ME permeated From EO microemulsion
gel and lipogel were 616.1 and 295.1 μg/cm2
respectively, compared with 260.5 and 248.8 μg/cm2
from oleic acid microemulsion gel and lipogel,
respectively. This may be due to increased solubility
of ME in oleic acid where it was 0.35 mg/ml and
2.42 mg/ml in EO and oleic acid respectively (Table
3), which lead to decreased partitioning of ME into
the skin and hence decreased permeation (21).
Our investigation revealed that meloxicam gels
have greater viscosity in oleic acid formulation than
EO formulation (Table 4). Consequently there was a
decreased release and permeation of ME from oleic
acid gels than EO gels. The result is in agreement
with that previously mentioned by Hüttenrauch et al
(22) and Ugri-Hunyavari and Erös (23). They stated
that, gel having a compact and close structure may
have a slower release rate than one of lower
consistency.
The enhanced drug release and permeation
properties from the hydroalcoholic carbopol gel
compared to the hydrogel, could be ascribed to two
FORMULATION AND EVALUATION OF MELOXICAM GELS
Feldene gel
EO lipogel
EO microemulsion gel
Oleic acid microemulsion gel
Oleic acid lipogel
500
400
2
Amount released (ug/cm )
factors; first, ethanol is a vehicle known to increase
the permeation of drugs through the skin either by
attacking the dense barrier structure of the skin (24)
or by augment the solubility and partitioning of the
drug in stratum corneum (25 ). Second, ethanol
decreases the viscosity of carpobol gel (Table 4)
which lead to improved drug release and permeation
from the gel (Figures 3 and 5). The results are in
agreement with the previous investigation performed
by Chi and Jun (26), who demonstrated that the
enhancement effect of ethanol in ketoprofen gel
formulations is due to decrease of viscosity and
increased solubility of drug in the gel.
Comparison of the results (Figures 2 and 3)
indicated that although there is a better in-vitro
release of piroxicam than meloxicam from their
formulations, figure 4 and 5 reflect inferior skin
permeation of the former. These results can be
attributed to the physicochemical properties of drugs
such as partition coefficient, vehicle solubility and
molecular weight which determine there permeation
through the complicated structure of the skin
(27,28).
159
300
200
100
0
0
0.5
1
1.5
2
2.5
Time1/2(hrs)
Figure 2. Release profiles of meloxicam from
different microemulsion gels and lipogels across
standard cellophane membrane in comparison with
feldene® gel. (n=3, mean + SE).
Feldene gel
Carbobol gel
Hydroalcoholic carbobol gel
500
Rabbit skin loaded with
sample (donor)
Cover with a small open
250 ml beaker
Shaking water
bath →
Figure 1. Cross-sectional diagram of the drug
permeation apparatus (Thermostatic shaker water
bath).
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
400
2
Amount released (ug / cm )
Effect of initial drug concentration:
Figure 6 and Table 2 show the effect of initial
drug concentration (0.5, 0.65, 1% w/w) on the
release and permeation of ME from EO microemulsion gel. The results revealed that increasing the
drug concentration, results in increasing the cumulative amount permeated. The cumulative amounts
permeated at 9 hrs were 133.6, 208.5 and 616.1
μg/cm2 for gel prepared with 0.5, 0.65, and 1% ME,
respectively. A close parallel results were reported
by Fergany (29).
300
200
100
0
0
0.5
1
1.5
Time
1/2
2
2.5
(hrs)
Figure 3. Release profiles of meloxicam from two
carbopol gels across standard cellophane membrane
in comparison with Feldene gel.
Anti-inflammatory activity of meloxicam gel:
Table 5 shows the inhibitory effects of ME gel
on the carrageenan- induced paw edema compared
with oral Mexicam® and Feldene® gel (0.5%
piroxicam). The data were reported as mean ± SEM
(n=4) and statistical analysis was carried out using
ANOVA-test at a level of significance of P< 0.05.
ME gel (EO microemulsion) produced significant
inhibitory effects, with a 42.37% inhibition after 4
hrs and the activity was approximately equivalent to
that of Mexicam® oral tablet, while more effective
160
EL-MEGRAB ET AL
Feldene gel
Carbopol gel
Hydroalcoholic carbopol gel
300
2
Amounte permeated (ug/cm )
than that of Feldene® gel. In this experiment, the
normal saline and the placebo gel had no effect on
carrageenan edema. ME gel significantly inhibited
inflammation in the treated paw and had also some
influence on edema of non-applied paw. While,
Feldene had no influence on edema of non-applied
paw indicating absence of any systemic effects.
These results were in agreement with that previously
mentioned by Gupta et al (1). They reported that,
meloxicam gel (1%w/w) showed increased
protection against inflammation as compared to
piroxicam (0.5 % w/w) and diclofenac (1% w/w)
gels.
250
200
150
100
50
0
0
2
4
6
8
10
Time (hr)
Feldene gel
EO lipogel
EO microemulsion gel
Oleic acid microemulsion gel
Oleic acid lipogel
Amount permeated (ug/cm2)
600
500
400
300
200
100
0
0
1
2
3
4
5
6
7
8
9
10
Time (hrs.)
meloxicam permeated (ug/cm2)
Figure 5. Permeation profiles of meloxicam from
two carbopol gels across abdominal rabbit skin in
comparison with Feldene® gel.
800
700
600
500
400
300
200
100
0
0
0.2
0.4
0.6
0.8
1
1.2
meloxicam concentration (W/W%)
Figure 4. Permeation profiles of meloxicam across
abdominal rabbit skin from different microemulsion
gels and lipogels in comparison with feldene® gel.
(n=3, mean + SE).
Figure 6. Effect of initial drug concentration on the
amount of meloxicam permeated from EO
microemulsion gel through abdominal rabbit skin.
Table 1: Components of different gel formulations.
Formula
Formula 1
Carbopol hydrogel
Formula 2
Carbopol hydroalcoholic gel
Formula 3
Microemulsion gel
Formula 4
Lipogel
Quantities by grams required to prepare 10 grams of gel
0.1 g corbopal, 9.9g (80 : 20%w/w) water : PG
0.1 g carbopol , 9.9g (40:40:20%w/w) water : PG : EOH
5g Tween80, 1g PG, 4g ethyl oleate or oleic acid, 2.5g water
1.5g monoglyceryl stearate, 8.5g ethyl oleate or oleic acid
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
FORMULATION AND EVALUATION OF MELOXICAM GELS
161
Table 2: Percutaneous permeation parameters of ME through abdominal rabbit skin from various
formulations (Mean ± SE, n = 3)
Formulation
Higuchi model
(r)
Microemulsion gel:
EO
Oleic acid
Lipogel:
EO
Oleic acid
Feldene®
(0.5% piroxicam gel)
Meloxicam (%)
0.5
0.65
1
Carbopol gel
Hydro alcoholic
carbopol gel
Cumulative
amount at 9hrs
(Q9h, μg/cm2)
Permeability
Coefficient
(Kp, Cm/hr × 10 -5)
0.98
0.98
616.1± 59.73
260.5±49.98
25.88±0.051
14.65±3.91
258.8±0.51
146.5±39.1
0.99
0.99
295.15 ±102.2
248.8 ± 35.85
15.2 ±10.7
17.23 ± 5.44
152
±107
172.3 ± 54.4
0.98
198.1 ± 1.2
11.89 ± 0.559
237.8 ± 11.18
0.99
0.98
0.98
133.6± 1.34
208.5± 15.77
616.1 ± 59.73
4.38± 0.05
6.1± 0.997
25.88 ± 0.051
87.6 ± 1.00
93.8 ± 19.94
258.8 ± 0.51
0.98
0.98
141.5
± 9.99
235.2 ± 19.93
6.34 ± 1.38
15.81 ± 0.655
63.4 ± 13.8
158.1 ± 6.55
Table 4: Viscosity measurements of different gel
bases (Mean ± SE, n=3)
Table 3: Solubility of ME in the oils.
Oil
Flux
(Jss, μg/cm2/hr)
Gel base
Microemulsion gel:
EO
Oleic acid
Lipogel:
EO
Oleic Acid
Carbopol gel
Hydroalcoholic carbopol gel
Feldene® gel
Solubility (mg/ml)
Ethyl oleate
0.355
Oleic acid
2.42
Viscosity (cp)
32313 ± 2899
74843± 5838
39403 ± 10946
144596 ± 1998
220612 ± 1156
131030 ± 7554
148080 ± 5071
Table 5: Evaluation of the anti-inflammatory activity of meloxicam microemulsion gel (Mean ± SE, n=4).
Sample
% Swelling (mean SEM)
% inhibition
Control 1
57.45 ± 3.95
-
Meloxicam tablet
33.54* ± 10.25
41.62
Treated foot
Non treated foot
Treated foot
Non treated foot
Control 2
46.28 ± 9.97
63.66
±18.53
EO microemulsion
26.67 ± 5.54*
50.73
± 13.3
Control 3
55.78
± 5.53
51.78
± 8.52
42.37
24.79
20.31
Zero
Feldene® gel
41.95
± 9.51*
59.34 ± 8.94
Control 1 = animals administered normal saline.
Control 2 = animals treated with placebo microemulsion gel.
Control 3 = animals treated with placebo HPMC gel.
P*< 0.05 compared with the control.
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
162
EL-MEGRAB ET AL
Conclusion
The results indicated that topical preparation of
miloxicam (EO microemulsion gel) could be an
effective topical dosage form beside its oral dosage
form (Mexicam® tablet) in inflammatory conditions
with the possibility of less systemic side effects.
13.
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