Formulation and Evaluation of Fast Dissolving Tablet of ... · Hardness - Hardness or tablet...

Article ID: WMC003121 ISSN 2046-1690

Formulation and Evaluation of Fast DissolvingTablet of Gliclazide using Combination ofSuperdisintegrantsCorresponding Author:Mrs. Rajeshree Panigrahi,Lecturer, Royal College of Pharmacy and Health Sciences , Andhapasara road, Berhampur, pin- 760002,760001 - India

Submitting Author:Mrs. Rajeshree Panigrahi,Lecturer, Royal College of Pharmacy and Health Sciences , Andhapasara road, Berhampur, pin- 760002,760001 - India

Article ID: WMC003121

Article Type: Research articles

Submitted on:29-Feb-2012, 11:08:12 AM GMT Published on: 29-Feb-2012, 02:49:25 PM GMT

Article URL: http://www.webmedcentral.com/article_view/3121

Subject Categories:PHARMACEUTICAL SCIENCES

Keywords:Fast dissolving tablet, Gliclazide, Wetting time, Water absorption ratio, Superdisintegrants,Disintegration time.

How to cite the article:Panigrahi R , Bhowmik M , Behera S , Choudhury P K, Chowdary K , Mishra G .Formulation and Evaluation of Fast Dissolving Tablet of Gliclazide using Combination of Superdisintegrants .WebmedCentral PHARMACEUTICAL SCIENCES 2012;3(2):WMC003121

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Formulation and Evaluation of Fast DissolvingTablet of Gliclazide using Combination ofSuperdisintegrantsAuthor(s): Panigrahi R , Bhowmik M , Behera S , Choudhury P K, Chowdary K , Mishra G

Abstract

Objective of this study was to formulate directlycompressible fast dissolving tablets of Gliclazide withsufficient mechanical integrity, content uniformity, andacceptable palatability to assist patients of any agegroup for easy administration. Effect of varyingconcentrations of different combination ofsuperdisintegrants such as crospovidone,crosscarmellose sodium, and sodium starch glycolateon disintegration time was studied. Tablets wereevaluated for weight variation, thickness, hardness,friability, taste, drug content, in vitro disintegrating timeand in vitro drug release. Other parameters such aswetting time, water absorption ratio were alsoevaluated. The disintegration time of the optimized C4batch was found to be 10.8 secs.

Introduction

Over a decade, the demand for development of fastdissolving tablet (FDTs) has enormously increased asit has significant impact on the patient compliance.Fast dissolving tablet offer an advantage forpopulations who have difficulty in swallowing. It hasbeen reported that dysphagia is common among allage groups and more specific with pediatric, geriatricpopulation along with institutionalized patients andpatients with nausea, vomiting, and motion sicknesscomplications[1]. Fast dissolving tablet with good tasteand flavor increase the acceptability of bitter drugs byvarious groups of population. Fast dissolving tablet arealso called as fast dissolving tablet, quickdisintegrating tablets, mouth dissolving tablets, fastdisintegrating tablets, rapid dissolving tablets, poroustablets, and rapimelts. However, of all the above terms,United States pharmacopoeia (USP) approved thesedosage forms as orally disintegrating tablets. Recently,European Pharmacopoeia has used the term fastdissolving tablet for tablets that disperses readily andwithin 3 min in mouth before swallowing [2, 3] . UnitedStates Food and Drug Administration (FDA) definedorally disintegrating tablet as “A solid dosage formcontaining medicinal substance or active ingredient

which disintegrates rapidly usually within a matter ofseconds when placed upon the tongue.” Thedisintegration time for orally disintegrating tabletsgenerally ranges from several seconds to about aminute [4, 5].

Evaluation of tablets

Hardness - Hardness or tablet crushing strength, the●

force required to break a tablet in a diametriccompression, was measured using Pfizer TabletHardness Tester [6-8]

Friability test - Friability of tablets was determined●

using Roche Friabilator. This device subjects thetablets to the combined effect of abrasion and shockin a plastic chamber revolving at 25 rpm anddropping the tablets at a height of 6 inches at eachrevolution. Pre-weighed sample of tablets wasplaced in a friabilator and the tablets were subjectedto 100 revolutions. Tablets were then dusted using asoft muslin cloth and reweighed [9-10].

Friability (F) = (1- Wo / W) x 100

Where,

Wo = weight of the tablets before the test.

W = weight of the tablet after the test.

Water absorption capacity - Water absorption ratio●

was determined by the following ratio

R = 100 x Wb / Wa

Where,

Wb = Weight of tablet before water absorption

W =Weight of tablet after water absorption

Wetting time - A piece of tissue paper folded twice●

was placed in a small Petri dish containing 6 ml ofwater. A tablet was put on the paper and the timerequired for complete wetting was measured[11, 12].In vitro disintegration time - Tablets were added to●

10 ml of Sorenson’s buffer solution of pH 6.28 at 37± 0.5°C. Time required for disintegration of thetablets was noted[13]

In vitro dissolution studies - Dissolution studies●

were carried out by USP-II dissolution apparatus.The tablet was taken from each formulation tocarry out the dissolution study in the pH 6.2 buffersolution as dissolution medium (pH of saliva)[14, 15]. Mouth feel: Mouth-feel is critical, and patients●

should receive a product that feels pleasant. Onetablet from each batch was tested for the sensation



by placing the tablet on the tongue. The healthyhuman volunteers were used for evaluation of mouthfeel. Taste evaluation was done by a panel of 5members using time intensity method. Sampleequivalent to 40 mg i.e. dose of drug was held inmouth for 10 secs. Taste were recorded instantlyand then after 10 secs, 1, 2, 4 and 6 minutes.Volunteer’s opinion for the taste were rated bygiving different score values i.e. 0 = good, 1 =tasteless, 2 = slightly bitter, 3 = bitter, 4 = awful.

Materials and Methods

Gliclazide was procured by Modern Lab., Indore(M.P.), Croscarmellose sodium, Crospovidone,Sodium starch glycolate, Microcrystalline cellulose aregifted by Signet chemical corporation, Mumbai,Magnesium stearate, Aerosil was procured by Nobleenterprises, Berhampur (Odisha).

FORMULATION OF FAST DISSOLVING TABLETSOF GLICLAZIDE

According to the formula given in Table 1, 3, 10 and12 a total number of twenty formulations wereprepared by direct compression method. All theingredients were passed through 60-mesh sieveseparately and collected, finally compressed intotablets after lubrication with magnesium stearate andaerosil by using 8 mm capilet punch using RIMEK 8station tablet compression machine. A combination oftwo superdisintegrants viz. crospovidone –croscarmellose, crospovidone – sodium starchglycolate were taken in 3% and 5% concentration indifferent ratios like 10:90, 25:75, 50:50, 75:25, 90:10respectively.

Results and Discussion

In the presence of disintegrants the matrix might bedistorted resulting in higher surface area, allowing thesuper disintegrant to readily pickup water & therebyrendering rapid rate of dissolution. The concentrationof superdisintegrants in the formulation also affects thedissolution rate.

The drug Gliclazide was exposed to a combination ofsuperdisintegrants as crospovidone – croscarmelloseand crospovidone – sodium starch glycolate in 3% and5% concentration in different ratios of 10:90, 25:75,50:50, 75:75 and 90:10 respectively. In case of CPV +CCM (3%) – 75:25 ratio was selected which showed9.5 secs D.T and 5.6 kg/cm2 Hardness, for CPV +SSG (3%) – 90:10 ratios was selected with 10.6 secsD.T and 4.83 kg/cm2 Hardness and for CPV + CCM(5%) – C15 90:10 ratio was selected which showed

28.3secs D.T and 6.4 kg/cm2 Hardness, for CPV +SSG (5%) – 50:50 ratios was selected with 33secsD.T and 6.06 kg/cm2 Hardness. Selected formulationswere exposed to t - test taking disintegration time intoconsideration. It was found that there is extremelysignificant difference in disintegration time among thetwo formulations. In-vitro dissolution of was carried outin phosphate buffer pH – 6.8. Formulation C4 containing CPV+CCM (3%) in 75:25 ratio showedmaximum drug release of 95.06% in 30 minscompared to other formulations and formulation C15containing CPV+CCM (5%) in 90:10 ratio showedmaximum drug release of 95.78 % in 30 minscompared to other formulations. Plots of log % drugremained Vs time were found to be linear. Dissolutiondata of the above formulations was exposed to drugrelease kinetics study. From the drug release kineticstudy it is found that the formulations exhibits firstorder release. Formulation C4 containing CPV+CCM(3%) in 75:25 ratio shows dissolution rate K1

0.0780min?1, half life (t ½) 8.88 mins, % D.E30 69.15%as shown respectively.

Conclusion

All the formulations fulfilled the official requirements ofhardness, disintegration time, wetting time and waterabsorption ratio. The formulation C4 was finallyselected to be the best formulation among all the otherformulations.

References

1. York, P., Drug Dev Ind Pharm, 1992, 18(6), 677-721.2. Block, L.H., Pharmacopoeial forum, 2009, 35(4),10268.3. Avachat, A., Ahire, V.J., Indian J Pharm Sci, 2007,69(1), 85-90.4. Reimerdes, D., Manuf chem, 1993, 64, 14-15.5. Jacob, S., Shirwaikar, A. A., Joseph, A., Srinivasan,K.K., Indian J Pharm Sci, 2007, 69 (5), 633-9. 6. Gohel, M.C., AAPS Pharm Sci Tech, 2007, 8(1),E1-E7.7. Seager, H., J. Pharm and Pharmacol, 1998, 50,375-382.8. Dobetti, L., Pharmtech, 2001, 37, 44-48.9. Habib, W., Khankari, R., Hontz, J., Crit Rev TherDrug Carrier Syst, 2000, 17, 61-72.10. Chakraborty, S., Khandi, M., Singh, S.P., Patra,N.C., Int. Journal of Green Pharmcy, 2008, 22-25.11. Mallikarjun, S. C., Prasad, D. V. K., Gupta, V. R.M., Indian Journal of Pharmaceutical Sciences,



2008,180-185.12. Jinichi, F., Etsuo, Y., Yasuo, Y., Katsuhide, T., Int.J Pharm, 2006, 3(10), 101-109.13. Sharma, S., Gupta, G.D., Asian J Pharma, 2008,2(1), 70-72.14. Jha, S.K., Vijayalakshmi, P., Karki, R., Goli, D.,Asian Jour. of Pharma, 2008, 2(4), 255-260. 15. Kuchekar, B.S., Badhan , A.C., Mahajan, H.S.,Indian Drugs, 2004, 41(10), 592-598.



FORMULA OF GLICLAZIDE FDT USING COMBINATION OFSUPERDISINTEGRANTS CPV+CCM (3%)

Ingredients

(mg)

C1

10:90

C2

25:75

C3

50:50

C4

75:25

C5

90:10

Gliclazide 80 80 80 80 80

MCC 59.5 59.5 59.5 59.5 59.5

CPV 0.45 1.125 2.25 3.375 4.05

CCM 4.05 3.375 2.25 1.125 0.45

Other excipients 6 6 6 6 6

Other excipients = Aerosil, Magnesium Stearate, Sod. Saccharin, Tartaric acid = 1.5mg each

Illustrations

Illustration 1

Table 1



EVALUATION OF GLICLAZIDE FDT USING COMBINATION OFSUPERDISINTEGRANTS CPV+CCM (3%)

Evaluation Hardnesskg/cm2

D.Tsecs

Wettingtime

Waterabs ratio

Friability%

Weightvariation

%

Mouth feel

C110:90

4.16 13 12.5 60.94 0.2 0.7 0

C225:75

5.5 13.7 12.8 50.03 0.2 0.3 0

C350:50

4.3 13.1 8.2 68.5 0.2 0.7 1

C475:25

5.6 9.5 6.5 87.3 0.4 0.7 0

C590:10

4.23 10.8 6.3 80.7 0.06 0.3 1

Illustration 2

Table 2



FORMULA OF GLICLAZIDE FDT USING COMBINATION OFSUPERDISINTEGRANTS CPV+ SSG (3%)

Ingredients(mg)

C610:90

C725:75

C850:50

C975:25

C1090:10

Gliclazide 80 80 80 80 80

MCC 59.5 59.5 59.5 59.5 59.5CPV 0.45 1.125 2.25 3.375 4.05SSG 4.05 3.375 2.25 1.125 0.45

Other excipients 6 6 6 6 6

Other excipients = Aerosil, Magnesium Stearate, Sod. Saccharin, Tartaric acid = 1.5mg each

Illustration 3

Table 3



EVALUATION OF GLICLAZIDE FDT USING COMBINATION OFSUPERDISINTEGRANTS CPV+ SSG (3%)


D.Tsecs

Wettingtime

Water absratio

Friability%

Weightvariation

%

Mouth feel

C610:90

3.5 10.6 6.5 80.09 0.06 0.4 3

C725:75

3.2 13 13 70.72 0.13 0.9 2

C850:50

4.16 9.3 6.3 30.92 0.06 0.8 0

C975:25

4.06 12.1 11.2 86.7 0.06 0.5 4

C1090:10

4.83 10.6 8.7 68.7 0.13 0.8 0

The formulation C4 and C10 were selected based on the hardness, disintegration time andwetting time parameters. These formulations were subjected to in-vitro drug releasestudies

Illustration 4

Table 4



CUMULATIVE % DRUG RELEASED PROFILE OF GLICLAZIDE FDTS INPHOSPHATE BUFFER PH 6.8

Time (mins) C4 C102 54.38 40.473 54.38 42.505 54.67 42.7910 67.14 50.3215 67.14 53.5130 95.06 92.16

Illustration 5

Table 5



LOG % DRUG RETAINED OF GLZ FDTS IN PHOSPHATE BUFFER PH 6.8 Time in

minsC4 C10

2 1.65 1.773 1.65 1.755 1.65 1.7510 1.51 1.6915 1.51 1.6630 0.69 0.89

Illustration 6

Table 6



DRUG RELEASED KINETICS OF GLICLAZIDE FDT USING COMBINATIONOF SUPERDISINTEGRANTS

PRODUCTCODE

Time Vs % drug release Time Vs Log % drugrelease

D.E.30 D.T

Slope R KOmg/mlmin?1

Slope R K1min?1

T1/2mins

(%) secs

C4 2.1661 0.793 2.1661 -0.0339 0.95 0.078 8.88 69.15 9.5C10 2.2831 0.886 2.2831 -0.0305 0.93 0.070 9.87 58.4 9.3

%D.E30 = % dissolution efficiency at time 30 mins

Illustration 7

Table 7



DISINTEGRATION TIME FOR FORMULATIONS CONTAININGCOMBINATION OF SUPERDISINTEGRANTS

C4 C109.50 9.309.70 9.509.50 9.329.70 9.509.55 9.30

Illustration 8

Table 8



t-TEST VALUES FOR THE SELECTED FORMULATIONS REPRESENTINGTHE DISINTEGRATION TIME

t-testP value 0.0142

Are means significantly different? (P < 0.05)" Yes

R squared

0.5491

One- or two-tailed P value? Two-tailed

Illustration 9

Table 9



FORMULA OF GLICLAZIDE MFDT USING CO-PROCESSEDSUPERDISINTEGRANTS CPV+CCM (5%)

Ingredients(mg)

10:90C11

25:75C12

50:50C13

75:25C14

90:10C15

Gliclazide 80 80 80 80 80MCC 56.5 56.5 56.5 56.5 56.5CPV 0.75 1.875 3.75 5.625 6.75CCM 6.75 5.625 3.75 1.875 0.75

Other excipients 6 6 6 6 6Other excipients = Aerosil, Magnesium Stearate, Sod. Saccharin, Tartaric acid = 1.5 mgeach

Illustration 10

Table 10



EVALUATION OF GLICLAZIDE MFDT USING CO-PROCESSEDSUPERDISINTEGRANTS CPV+CCM (5%)


D.Tsecs

Wettingtime

Waterabs ratio

Friability%

Weightvariation %

Mouth feel

C1110:90

4.13 71 43 39.91 0.55 0.61 0

C1225:75

3.6 59 31.3 60.54 0.68 0.78 1

C1350:50

6.5 46 36 55.86 0.69 0.551 4

C1475:25

4.16 38.8 30.6 58.01 2.7 0.98 2

C1590:10

6.4 28.3 23.7 67.04 0.69 0.7 0

Illustration 11

Table 11



FORMULA OF GLICLAZIDE MFDT USING CO-PROCESSEDSUPERDISINTEGRANTS CPV+SSG (5%)

Ingredients(mg)

C1610:90

C1725:75

C1850:50

C1975:25

C2090:10

Gliclazide 80 80 80 80 80MCC 56.5 56.5 56.5 56.5 56.5CPV 0.75 1.875 3.75 5.625 6.75SSG 6.75 5.625 3.75 1.875 0.75

Other excipients 6 6 6 6 6 Other excipients = Aerosil, Magnesium Stearate, Sod. Saccharin, Tartaric acid = 1.5 mgeach

Illustration 12

Table 12



EVALUATION OF GLICLAZIDE MFDT USING CO-PROCESSEDSUPERDISINTEGRANTS CPV+SSG (5%)


D.Tsecs

Wettingtime

Waterabs ratio

Friability%

Weightvariation %

Mouthfeel

C1610:90

5.83 49.7 31.5 54.37 10.5 0.614 2

C1725:75

6.16 52 43.2 58.87 0.75 0.54 3

C1850:50

6.06 33 21 71.37 0.55 0.78 0

C1975:25

5 38.5 19 68.02 0.69 0.98 0

C2090:10

5.33 42 24.6 60.92 0.76 0.6 4

The formulation C15 and C18 were selected based on the hardness, disintegration timeand wetting time parameters. These formulations were subjected to in-vitro drug releasestudies

Illustration 13

Table 13




Time (mins) C15 C182 43.95 41.923 50.61 50.615 57.08 55.3410 60.61 60.6115 82.55 85.9830 95.78 95.98

Illustration 14

Table 14



LOG % DRUG RETAINED OF GLZ FDTS IN PHOSPHATE BUFFER PH 6.8 Time in

minsC15 C18

2 1.74 1.763 1.74 1.765 1.73 1.7210 1.71 1.6915 1.69 1.6930 1.63 1.64

Illustration 15

Table 15



DRUG RELEASED KINETICS OF GLICLAZIDE FDT USING COMBINATIONOF SUPERDISINTEGRANTS

PRODUCTCODE

Time Vs % drug release Time Vs Log % drugrelease

D.E.30 D.T

Slope R KOmg/mlmin?1

Slope R K1min?1

T1/2mins

(%) secs

C15 1.0846 0.604 1.0846 -0.0042 0.99 0.009 72.18 30.93 28.3C18 1.0623 0.595 1.0623 -0.0039 0.93 0.008 77.86 48.73 33

%D.E30 = % dissolution efficiency at time 30 mins

Illustration 16

Table 16



DISINTEGRATION TIME FOR FORMULATIONS CONTAININGCOMBINATION OF SUPERDISINTEGRANTS

C15 C1828.30 3328.50 3528.31 32.928.50 3328.30 35

Illustration 17

Table 17



t-TEST VALUES FOR THE SELECTED FORMULATIONS REPRESENTINGTHE DISINTEGRATION TIME

t-testP value 0.0005

Are means significantly different? (P < 0.05)" Yes

R squared

0.9356

One- or two-tailed P value? Two-tailed

Illustration 18

Table 18




Illustration 19

Figure 1



LOG % DRUG RETAINED GRAPH OF GLZ FDTS IN PHOSPHATE BUFFERPH 6.8

Illustration 20

Figure 2



- t – TEST FOR THE SELECTED FORMULATIONS REPRESENTING THEDISINTEGRATION TIME

Illustration 21

Figure 3



CUMULATIVE % DRUG RELEASED PROFILE OF GLICLAZIDE FDTS IN

PHOSPHATE BUFFER PH 6.8

Illustration 22

Figure 4



LOG % DRUG RETAINED GRAPH OF GLZ FDTS IN PHOSPHATE BUFFER

PH 6.8

Illustration 23

Figure 5



t – TEST FOR THE SELECTED FORMULATIONS REPRESENTING THE

DISINTEGRATION TIME

Illustration 24

Figure 6



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