formulation and evaluation of chlorzoxazone … · 2015-04-17 · * lavanya.v et al; formulation...

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

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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: [email protected]

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.

mailto:[email protected]

* 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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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



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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



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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



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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



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Graph of Dissolution Studies

Fig No.5 Graph of Dissolution studies

Fig No.6 Zero order kinetic graph



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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



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*Corresponding author address:

Lavanya.V*

*Department of Pharmaceutics,

Vathsalya College of pharmacy, Anantharam,

Bhongir , Nalgonda-508116, Andhra Pradesh, India

formulation and evaluation of chlorzoxazone … · 2015-04-17 · * lavanya.v et al; formulation...

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