Formulation and evaluation of Isoniazide Dispersible tablets using Natural substances as Disintegrants

BS Kuchekar, SR Pattan, RK Godge, RB Laware, NS Dighe SK Parjane and AN Merekar*

Dept. of Pharmaceutics. Pravara Rural College of Pharmacy, Pravaranagar.

*Corresponding Author E-mail: anmerekar@ yahoo.co.in

 

ABSTRACT

Dispersible tablets of Isoniazide were prepared using natural substances as disintegrant such as Ispaghula husk powder, Cassia tora powder, Cassia tora powder (defatted), Cassia nodosa powder in different concentration by direct compression method. Formulations were evaluated for the standard of dispersible tablets and were compared with marketed products. It was observed that all the formulations were acceptable with reasonable limits of standard required for dispersible tablets. The study reveals that natural gums used as disintegrants were effective in low concentration.

 

KEYWORDS: Dispersible tablet, direct compression, Isoniazid, natural disintegrants.

 


INTRODUCTION:

Dispersible tablets are uncoated tablets that produce a uniform dispersion or suspension in water at room temperature without stirring. With the increase in the average human life span, drug administration for elderly patients has become more important .Due to decline in swallowing ability with age; a great many elderly patients complain that it is difficult to take medication in the form tablets. Recently useful dosage form such as rapidly disintegrating or dissolving tablet, have been developed and applied clinically. The dispersible tablets allow dissolution or dispersion in water prior to administration. Dispersible   tablets    are   easier to administer   or    swallow    than    capsules for pediatric, dysphasic patients, mentally ill, unco-operative and nauseated patients, those with conditions of motion sickness, sudden episodes of allergic attack or coughing. Some times it may be difficult to swallow conventional products due to unavailability of water.

 

Isoniazide is a white, crystalline powder or colourless, odourless crystals which is freely soluble in water; sparingly soluble in ethanol (95%), slightly soluble in chloroform, very slightly soluble in ether.

 

Ispaghula husk consists of drid seeds of the plant known as Plantago ovata. It contains mucilage which is present in epidermis of the seed1-5. Some of the material such as Cassia tora and Cassia nodosa6-9, which are nontoxic in nature, have nutritional value and used in the food material.

 

The present investigation was carried out to prepare dispersible tablets of Isoniazide using Plantago ovata seed husk (Isapghula), Cassia tora and Cassia nodosa as a disintegrants to establish standards required for the dispersible tablet, to optimize the effective concentration of the disintegrant and to compare the formulations with marketed product.

 

MATERIALS AND METHODS:

Isoniazide was provided as a gift sample by Lupin Pvt. Limited, Mumbai, Ispaghula husk powder, Cassia tora powder, Cassia nodosa powder were provided by Prasad Traders Pusad and Gautam Global, Dehra Dun, India authenticated by Agarkar research institute, pune.  All the materials used were of standard analytical grade.

 

Method:

A) Preparation of Dispersible Tablet10-12:

Dispersible tablets of Isoniazid were prepared using direct compression method after incorporating different disintegrant named as Ispaghula husk powder, cassia tora powder, cassia tora defatted powder, cassia nodosa powder in a concentration 5%, 10%. 15%. The composition of formulation is given in Table No 1.The ingredients were thoroughly mixed and passed through sieve no. 22.

 

B) Evaluation of Formulated Tablet:

The various formulations were evaluated for hardness, weight variation, friability, disintegration time, Invitro disintegration time, wetting time, uniformity of dispersion, drug content/content uniformity, and dissolution study.

 

Disintegration time was determined using Thermonic Tablet Disintegration apparatus USP using distilled water as a disintegration medium. Each formulation was tested for uniform dispersion as per official standards. After disintegration beaker was shaken and this fluid was passed


Table1: Formulation of Dispersible Tablet of Isoniazid:

Ingredients mg/ tab

Formulation of DT of Isoniazide

I

IH1

I

IH2

I

IH3

I

CT1

I

CT2

I

CT3

I

CTD1

I

CTD2

I

CTD3

I

CN1

I

CN2

I

CN3

Isoniazide

100

100

100

100

100

100

100

100

100

100

100

100

Lactose

117.5

105

92.5

117.5

105

92.5

117.5

105

92.5

117.5

105

92.5

Isapghula Husk

12.5

25

37.5

-

-

-

-

-

-

-

-

-

Cassia Tora

-

-

-

12.5

25

37.5

-

-

-

-

-

-

Cassia Tora (DF)

-

-

-

-

-

-

12.5

25

37.5

-

-

-

Cassia Nodosa

-

-

-

-

-

-

-

-

-

12.5

25

37.5

Talc

10

10

10

10

10

10

10

10

10

10

10

10

Mag. Stearate

10

10

10

10

10

10

10

10

10

10

10

10

(Where I IH Is DT Isoniazid With Ispaghula Husk, ICT Is DT Isoniazid With Cassia Tora, ICTD Is DT Isoniazid With Cassia Tora(Defatted), ICN Is DT Isoniazid With Cassia Nodosa, 1,2,3 Indicates  5%,10%,15% Concentration Respectively)

 

Table2: Evaluations date of formulated dispersible tablet of Isoniazid.

Formulation

Hardness Kg/cm 2 (n=3)

Friability (%) (n=3)

Wt. Variation

(%) (n=3)

Disinteg. Time (Sec) (n=3)

Wetting Time

(Sec) (n=3)

Drug Content

±SD (n=3)

I IH 1

3.16

0.44

0.18

30

137

99.5±0.018

I IH 2

3.00

0.60

0.27

37

150

99.5±0.027

I IH 3

3.36

0.39

0.30

39

163

99.0±0.011

ICT 1

2.96

0.48

0.27

60

203

99.5±0.027

ICT2

3.16

0.44

0.31

72

227

99.0±0.027

ICT3

3.40

0.51

0.38

89

240

99.0±0.001

ICTD 1

3.13

0.76

0.47

70

210

99.5±0.030

ICTD2

3.43

0.38

0.50

85

235

99.0±0.027

ICTD3

3.26

0.32

0.53

93

244

99.3±0.001

ICN 1

2.96

0.36

0.24

40

153

99.1±0.019

ICN2

3.50

0.40

0.31

50

160

99.1±0.027

ICN3

3.13

0.48

0.35

73

173

99.0±0.001

I MKTD

3.66

0.30

0.34

130

210

99.5±0.027

(Where I IH Is DT Isoniazid With Ispaghula Husk, ICT Is DT Isoniazid With Cassia Tora, ICTD Is DT Isoniazid With Cassia Tora(Defatted), ICN Is DT Isoniazid With Cassia Nodosa, I MKTD Is Marketed DT Isoniazid ,1,2,3 Indicates  5%,10%,15% Concentration Respectively)

 


Figure1 (a) Cumulative %Drug Release of Isoniazid Tablet Containing Ispaghula  Husk as Disintegrant 

 

through the sieve no.22. Hardness of the tablet was tested Pfizer hardness tester and friability by Roche Friabilator. Drug content was determined by using UV spectrometer (Shimadzu) at 263 nm.  The evaluation parameters shown in Table No 2, Comparison of Cumulative % Drug Release of Formulated and Marketed Isoniazid Dispersible Tablet was shown in figure 1.

 

C) Dissolution studies:

Dissolution studies were performed using a dissolution test apparatus USP XXII. (Basket assembly) at 100 rpm using 900 ml of water and temperature was maintained at 37+ 0.50 through out the study. Ten millimeter of the sample was withdrawn at a regular interval and replaced with an equal volume of phosphate buffer. Samples were filtered and drug content was estimated by UV spectrophotometer at 263nm. Disslution data shown in table 3.


 

Figure1 (b) Cumulative %Drug Release of Isoniazid Tablet Containing Cassia Tora as Disintegrant

 

Figure1(c) Cumulative %Drug Release of Isoniazid Tablet Containing Cassia tora as Disintegrant

 

 Figure1 (d) Cumulative %Drug Release of Isoniazid Tablet Containing Cassia nodosa as Disintegrant

 

RESULT AND DISCUSSION:

The % drug content was found to be between 99.00% to 100.00%, which was within acceptable limits. The hardness was found to be 2.5Kg/ cm2 to 4.0 Kg/ cm2. Percent friability was less than 1% in the entire formulation and values obtained lies between 0.32 –0.76. All the formulations disintegrated between 30-130 seconds. Disintegration pattern of the IH, CT, CTD, and CN showed satisfactory and uniform dissolution Fig.2.

 

The study reveals that formulations prepared by using 5% Isapghula husk exhibited good dissolution and uniform dispersion characteristics necessary for dispersion tablets as compared to marketed, convential tablets of Isoniazide.

 

Table 3:  In Vitro Study of Selected Formulated and Marketed dispersible Tablet of Isoniazid.

Formulation

Code

Time

(Min)

Dissolution Efficiency (%)

Uniformity of Dispersion

 

 

I IH 1

1

 

 

92.98

 

 

PASSES

2

3

4

5

 

 

 

ICT 1

1

 

 

80.10

 

 

PASSES

2

3

4

5

 

 

 

ICTD 1

1

 

 

77.24

 

 

PASSES

2

3

4

5

 

 

 

ICN 1

1

 

 

82.96

 

 

PASSES

2

3

4

5

 

 

 

I MKTD

1

 

 

88.98

 

 

PASSES

2

3

4

5

 

(Where I IH Is DT Isoniazid With Ispaghula Husk, ICT Is DT Isoniazid With Cassia Tora, ICTD Is DT Isoniazid With Cassia Tora(Defatted), ICN Is DT Isoniazid With Cassia Nodosa, I MKTD Is Marketed DT Isoniazid ,1 Indicates  5%Concentration Respectively)

 

CONCLUSION:

In conclusion, overall result suggests that a 5% Isapghula husk shows better disintegration as compared to marketed.

 

ACKNOWLEDGEMENT:

The author thanks to Lupin Lab. Pvt. Limited, Mumbai, for providing Isoniazide as a gift sample also thankful Shri Balasaheb Vikhe patil. ,Chairman, Dr S.R Walunj Secretry,Pravara Rural Education Society for their constant encouragement.

 

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Received on 16.06.2009       Modified on 20.07.2009

Accepted on 22.08.2009      © RJPT All right reserved

Research J. Pharm. and Tech.2 (3): July-Sept. 2009,;Page 585-588