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International Journal of Pharmaceutical
Biological and Chemical Sciences
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS)
| JAN-MAR 2013 | VOLUME 2 | ISSUE 1 | 10 - 17
www.ijpbcs.net
Research Article
Pag
e10
FORMULATION AND EVALUATION OF CHLORZOXAZONE SUSTAINED RELEASE
TABLETS BY USING HYDROPHILIC POLYEMERS
Lavanya.V*1, Saritha.D
1, Vishnupriya.A
1
*Department of Pharmaceutics, Vathsalya College of pharmacy, Anantharam,
Bhongir, Nalgonda-508116, Andhra Pradesh, India
*Corresponding Author Email: Lavanyaredde@gmail.com
INTRODUCTION
Sustained release dosage forms provide less dosage
frequency, increased efficacy and constant delivery. The
goal in designing sustained release formulation is to
control the rate of drug release and to maintain desire
drug level in the blood which is therapeutically effective
for an extended period of time. Thus the reduction of
both total dose of drug administered and the incidence of
adverse side effects, better patient compliance can be
achieved.1, 2
Chlorzoxazone (5-chloro-2, 3-dihydro-1, 3-benzoxazol-
2- one) is a centrally acting muscle relaxant used to treat
muscle spasm and the resulting pain and discomfort 3.
Chlorzoxazone inhibits degranulation of mast cells,
subsequently preventing the release of histamine and
slow-reacting substance of anaphylaxis (SRS-A),
mediators of type I allergic reactions. Chlorzoxazone
also may reduce the release of inflammatory
leukotrienes. Chlorzoxazone may act by inhibiting
calcium and potassium influx which would lead to
neuronal inhibition and muscle relaxation. It is having a
shorter half life (1.1hour) with the dose (250-750mg)
administration of 3-4 times a day. Sustained release
tablets can be prepared by direct compression method
using hydrophilic polymers such as HPMCK4M,
Carbopol 971P, Carbopol 974P.
MATERIALS AND METHODS
MATERIALS
Chlorzoxazone was obtained as a gift sample from Drugs
India, Hyderabad. Hydroxy propyl methyl cellulose
K4M was obtained as a gift sample from Loba Chem
Pvt. Ltd, Mumbai. Carbopol 971P, Carbopol 974P,
Lactose, Micocrystalline cellulose, Carbomer, Talc,
Magnesium stearate were obtained as gift samples from
S.D.Fine Chem.Ltd.,Mumbai. All other chemicals and
solvents were purchased from analytical grade.
METHODS
Chlorzoxazone sustained release tablets were prepared
by direct compression method. The drug, polymers and
other ingredients were weighed accurately and passed
through sieve no.30. The content was mixed thoroughly
in a mixer for 10mins, to this add lubricant, and glidant
again mixed for 5mins. The mixture was directly
compressed into tablets using suitable flat –faced punch
and die set on a single punch tablet compression
machine.
EVALUATION PARAMETERS
1. Bulk density:
It is the ratio of total mass of powder to the bulk volume
of powder. It was measured by pouring the weighed
ABSTRACT:
The present study was aimed to formulate and evaluate the Chlorzoxazone sustained release tablet using
polymers such as HPMCK4M, CARBOPOL 971P, CARBOPOL 974P, in order to decrease the dosing
frequency. Chlorzoxazone is a centrally acting muscle relaxant used to treat muscle spasm and the resulting pain
and discomfort; it is having shorter half-life (1.1hr) with dose administration (250-750mg) of 3-4 times a day.
Tablets were prepared by direct compression method and evaluated by different parameters such as weight
variation, hardness, friability, thickness, drug content uniformity and in vitro drug release study. All the tablets
passed the tests. The interaction between drug and polymers were determined by using FTIR studies. The
FTIR study reveals that there is no interaction between drug and polymers. Based on invitro drug release study
F3 formulation showed sustained release effect up to 12hours compared to other formulations. The drug release
pattern was followed by krosmeyer –peppas model for F3 formulation which indicates the diffusion mechanism.
KEYWORDS: Chlorzoxazone, HPMCK4M, CARBOPOL 971P, CARBOPOL 974P, Sustained release. Direct compression method.
* Lavanya.V et al; Formulation And Evaluation Of Chlorzoxazone Sustained Release Tablets By Using Hydrophilic Polymers
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JAN-MAR 2013 | VOLUME 2 | ISSUE 1 | 10-17 | www.ijpbcs.net
Pag
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powder into a measuring cylinder and the volume was
noted. It is expressed in gm/ml.
Bulk density = Weight of powder / Bulk volume
2. Tapped density:
It is the ratio of total mass of powder to the tapped
volume of powder. It is determined by placing a
graduated cylinder containing known weight of powder,
mechanical tapper apparatus operated for fixed number
of taps until the powder bed volume has reached a
minimum volume.
Tapped density = Weight of powder / Tapped volume
3. Carr’s Index (I):
It is measured by using values of bulk density and tapped
density.
density Tapped
density Bulk -density Tapped
×100
4. Hausner’s ratio:
Hausner’s ratio is the ratio of tapped density to bulk
density.
Hausner’s Ratio = DensityBulk
Density Tapped
5. Angle of Repose:
The frictional forces in a loose powder can be measured
by the angle of repose, θ.
= tan-1
(h/r)
Where,
h=height of the heap
r=radius of the heap
It is determined by pouring the powder a conical on a
level, flat surface, measured the included angle with the
horizontal.
6. Hardness:
The hardness of the tablet was determined by using a
Monsanto hardness tester. It is expressed in Kg / cm2.
7. Thickness4:
The thickness of the tablets was measured by Digital
Vernier Caliper. It is expressed in mm.
8. Weight Variation4:
Twenty tablets were selected randomly from each
formulation and weighed by using electronic balance and
the test was performed according to official method.
9. Friability (F):
The friability of the tablet was determined using Roche
Friabilator. It is expressed in %. 10 tablets were initially
weighed and transferred into the friabilator. The
friabilator was operated at 25 rpm for 4 mins. The tablets
were weighed again. Friability of tablet should not
exceed 1%.
10. Determination of drug content
Weigh and powdered 10 tablets in a mortar. From this
powder equivalent to 750mg of Chlorzoxazone was
taken in a 100ml volumetric flask to this 5 ml of
methanol was added and then the solution was subjected
to sonication for about 10min for complete solubilization
of drug and the solution was made up to the mark with
methanol, filtered and further appropriate dilutions were
made with phosphate buffer (pH 6.8) and the drug
content was estimated by measuring the absorbance at
282.6 nm by using UV-Visible spectrophotometer.
11. Drug-Excipient Interaction Studies5
This type of interactions were studied with the help of
Shimadzu FTIR spectrophotometer, in which KBR pellet
method used to determine the interactions.
12. In vitro dissolution studies6
The dissolution studies were performed using USP 24
type 2 paddle apparatus , employing paddle stirrer
rotating at 75 rpm, 900 ml of 0.1N HCl for first 2hrs
and phosphate buffer ( pH 6.8) for the remaining hours
as a dissolution medium at 37 ± 0.5ºC. 5 ml aliquots of
dissolution medium was withdrawn at specified time
intervals and the volume of the dissolution medium was
maintained by adding the same volume of fresh
dissolution medium. The absorbance of the withdrawn
samples was measured spectro photometrically at 282.6
nm.
13. Drug release kinetics7
To analyze the mechanism of drug release from the
tablets, the results of in vitro release data were plotted in
various kinetic models like zero order, Higuchi model
and Krosmeyer- peppas.
14. Stability studies
The stability studies were conducted for satisfactory
formulation as per ICH guidelines. The satisfactory
formulation sealed in aluminum packaging and stored at
30±2°C with 65±5% RH for 2months.Samples were
analyzed for physical parameters and drug content.
RESULTS AND DISCUSSION
Evaluation parameters
Tablets of different formulations were subjected to
various physicochemical evaluation parameters such as
weight variation, hardness, friability, thickness, drug
content, and diameter. The results of these studies were
found to be within the limits and given in Table No.3.
Compatibility studies
The standard spectrum of chlorzoxazone shown in fig.1
was compared by FTIR spectrum of physical mixtures
Fig2, 3; 4.FTIR studies proved that the drug is
compatable with excipients.
In vitro dissolution studies
The results of dissolution studies for different
formulations from F1 to F9 were showed in Fig.5.The
formulations F1, F4, F7 shows 100%drug release within
* Lavanya.V et al; Formulation And Evaluation Of Chlorzoxazone Sustained Release Tablets By Using Hydrophilic Polymers
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JAN-MAR 2013 | VOLUME 2 | ISSUE 1 | 10-17 | www.ijpbcs.net
Pag
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8hrs, formulations F2, F5, F8 shows 100% drug release
within 10hrs where as formulations F3, F6, F9shows
sustained release up to 12hrs which were found to be
F3,F6,F9. Among all formulations F3 showed good
sustained release. The Invitro dissolution studies
revealed that drug release rate was retarded with
proportional to polymer concentration. The amount of
polymer influences drug release showed in Fig.5.
Drug release kinetics
The release data was fitted to various mathematical
models to evaluate the kinetics and the mechanism of
drug release. The data was analyzed for the optimized
formulation F3, Among the models, zero order, first
order,Higuchi,and Krosmeyer peppas the formulation F3
was best fitted in Krosmeyer-peppas and its r2value was
found to be 0.993 which indicates diffusion is the
mechanism of drug release.
Stability studies
F3 formulation was subjected to stability studies. It was
suggested that there was no significant change physical
parameters such as weight variation, hardness, friability,
thickness; drug content. Which is shown in Table No 5.
CONCLUSION
From the above study it may be concluded that at higher
concentration of HPMC K4M, CARBOPOL (971P,
974P) were retarded the release of chlorzoxazone. As the
concentration of polymer increases drug release was
retarded. Hence the polymer concentrations were
optimized to produce the oral SR tablets of
Chlorzoxazone.
REFERENCES
1. Brahmankar, D.M., Sunil B, Jaiswal ., Biopharmaceutics
and Pharmacokinetics, 1995, 335-338.
2. Shanmugam, S., Ramya Chakrahari., Int. J. PharmTech
Res. 2011, 3, 526-527.
3. Dong, D.L., Luan, Y., Feng, T.M., Fan, C.L., Yue, P.,
Yang, B.F.,Eur J Pharmacol. 2006, 545, 161–166.
4. Lakade, S.H., Bhalekar, M.R., Research J. Pharm. &
Tech. 2008, 1 (4), 410-413.
5. Raghavendra Rao, N.G., Ashok Yadav., Int J. Pharm &
Res. 2010, 2(1), 34-42.
6. Lakshmana Prabu, S., Shirwaikar, A.A., Shirwaikar A.,
Ars Pharm.2009, 50 (1), 32- 42.
7. Clement Jackson, Musiliu Adedokun., Int J Pharm Pharm
Sci. 2011, 3 (5), 64-67.
Table No 1 Composition of Chlorzoxazone SR tablet formulations
INGREDIENTS(mg/tablet) F1 F2 F3 F4 F5 F6 F7 F8 F9
Chlorzoxazone 750 750 750 750 750 750 750 750 750
HPMCK4M 70 90 110 - - - - - -
CARBOPOL 971P - - - 70 90 110 - - -
CARBOPOL 974P - - - - - - 70 90 110
Lactose 130 110 90 130 110 90 130 110 90
Microcrystalline cellulose 50 50 50 50 50 50 50 50 50
Carbomer 50 50 50 50 50 50 50 50 50
Magnesium stearate 5 5 5 5 5 5 5 5 5
Talc 3 3 3 3 3 3 3 3 3
Total(mg) 1058 1058 1058 1058 1058 1058 1058 1058 1058
Table No 2 Preformulation parameters of Chlorzoxazone
Bulk density(gm/cc) 0.436 0.528 0.45 0.44 0.57 0.42 0.46 0.55 0.53
Tapped density(gm/cc) 0.524 0.6 0.53 0.52 0.63 0.48 0.52 0.62 0.6
Angle of repose(Ө) 25°.46' 26°.50' 23°.26' 27°.75' 23°.49' 26°.56' 25°.25' 24°.24' 23°.31'
Compressibility index (%) 16.7 12 17.77 15.38 9.52 12.86 11.53 11.29 11.66
Hausners' ratio 1.2 1.13 1.17 1.18 1.1 1.14 1.13 1.12 1.13
* Lavanya.V et al; Formulation And Evaluation Of Chlorzoxazone Sustained Release Tablets By Using Hydrophilic Polymers
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JAN-MAR 2013 | VOLUME 2 | ISSUE 1 | 10-17 | www.ijpbcs.net
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Table No 3 Evaluation studies of Chlorzoxazone
Formulation Weight
variation(mg)
Hardness
(kg/cm²)
Friability (%) Thickness
(mm)
Drug content
(%)
F1 1058.1±0.44 5.2 0.42 5.37 98.8
F2 1057.85±0.36 5.5 0.28 5.37 99.7
F3 1058±0.45 5.2 0.35 5.37 98.8
F4 1058.1±0.30 5.3 0.24 5.34 99.3
F5 1057.95±0.39 5.2 0.31 5.38 99.7
F6 1058.05±0.22 5.4 0.47 5.37 97.7
F7 1058.15±0.36 5.2 0.32 5.38 98.8
F8 1058.05±0.39 5.3 0.49 5.37 97.4
F9 1058±0.324 5.3 0.38 5.38 98.4
Table No 4 Dissolution tables of formulations
Time
(hrs) F1 F2 F3 F4 F5 F6 F7 F8 F9
0 0 0 0 0 0 0 0 0 0
1 5.52 6.12 1.30 4.2 2.38 2.41 5.55 4.38 3.78
2 8.07 7.2 2.50 8.4 7.08 4.32 9.24 6.87 5.76
3 26.16 24.36 8.52 28.08 20.28 11.4 21.96 15.36 12.48
4 42.54 33.96 17.64 38.46 38.28 17.6 34.68 31.08 23.76
5 58.5 48.96 26.88 53.76 44.64 29.06 52.56 36.84 32.94
6 73.8 56.88 35.64 72.6 59.4 39.6 62.4 47.28 41.1
7 86.4 65.4 42.36 83.4 64.2 48.8 82.2 63.6 57.1
8 92.4 70.8 58.2 91.2 76.2 51.96 96 78 63.6
9 85.8 64.8 88.8 68.4 84 74.4
10 91.8 77.4 93.6 78.6 93 80.4
11 89.4 89.4 88.2
12 97.8 95.4 94.2
STABILITY STUDIES
Table No.5 Stability studies:
Fig No.1FTIR Spectrum of Chlorzoxazone
Formulation Parameters At room
temperature
30±20c/65±5%RH
after 1 month
30±20c/65±5%RH after s 2
nd
month
F3 Appearance white white white
Drug content 98.8 98.1 97.7
* Lavanya.V et al; Formulation And Evaluation Of Chlorzoxazone Sustained Release Tablets By Using Hydrophilic Polymers
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JAN-MAR 2013 | VOLUME 2 | ISSUE 1 | 10-17 | www.ijpbcs.net
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Fig No 2.FTIR Spectrum of physical mixture (Chlorzoxazone and HPMCK4M)
Fig No.3 FTIR spectrum of physical mixture (Chlorzoxazone and Carbopol 971P)
Fig No.4 FTIR spectrum of physical mixture (Chlorzoxazone and Carbopol 974P)
FIGURES
* Lavanya.V et al; Formulation And Evaluation Of Chlorzoxazone Sustained Release Tablets By Using Hydrophilic Polymers
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JAN-MAR 2013 | VOLUME 2 | ISSUE 1 | 10-17 | www.ijpbcs.net
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Graph of Dissolution Studies
Fig No.5 Graph of Dissolution studies
Fig No.6 Zero order kinetic graph
* Lavanya.V et al; Formulation And Evaluation Of Chlorzoxazone Sustained Release Tablets By Using Hydrophilic Polymers
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JAN-MAR 2013 | VOLUME 2 | ISSUE 1 | 10-17 | www.ijpbcs.net
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Fig No.7 First order kinetic graph
Fig No.8 Higuchi equation graph
Fig No. 9 korsemeyer –Peppas kinetic graph
R² = 0.992
0
0.5
1
1.5
2
2.5
0 2 4 6 8 10 12 14
Log
% r
em
ain
ing
CD
R
Time(hr)
R² = 0.993n=0.75
0
0.5
1
1.5
2
2.5
0 0.2 0.4 0.6 0.8 1 1.2
Log
% c
um
ula
tive
dru
g re
leas
e
Log time
* Lavanya.V et al; Formulation And Evaluation Of Chlorzoxazone Sustained Release Tablets By Using Hydrophilic Polymers
International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS) | JAN-MAR 2013 | VOLUME 2 | ISSUE 1 | 10-17 | www.ijpbcs.net
Pag
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*Corresponding author address:
Lavanya.V*
*Department of Pharmaceutics,
Vathsalya College of pharmacy, Anantharam,
Bhongir , Nalgonda-508116, Andhra Pradesh, India
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