Formulation and Evaluation of Valsartan Fast Dissolving Tablets

 

A. Pavan Kumar*, J. Satyanaryana, V. Sai Kishore and T.E. Gopala Krishna Murthy

Bapatla College of Pharmacy, Bapatla-522101

*Corresponding Author E-mail: pavan.hai@gmail.com.

 

ABSTRACT:

Valsartan is an ACE inhibitor and effectively used in the treatment of hypertension. Valsartan is a poorly soluble drug, belonging to biopharmaceutical classification- II and dissolution is the rate limiting step for drug absorption. Valsartan fast dissolving tablets are formulated to overcome its poor solubility. Nature and concentration of the superdisintegrant and type of diluent influence the rate of dissolution. The present research focused the influence of concentration of the superdisintegrant and diluents on rate of drug release from the Valsartan fast dissolving tablets. The rate of drug release was found to be increased by increasing the concentration of the superdisintegrant and found to be highest for tablets formulated with Crospovidone 5%. The rate of drug release was found to be more for tablets formulated by spray dried lactose than compared to tablets formulated by Mannitol and Microcrystalline cellulose.

 

KEYWORDS: Valsartan , Crospovidone, Fast dissolving tablets.

 


 

INTRODUCTION:

Solid dosage forms are most popular because of their higher patient compliance. Eventhough solid dosage forms are not suited for the patients who are suffering with the dysphagia, nausea, vomiting and motion sickness. These are also not suited for geriatrics and pediatrics. In order to overcome the above problems orodispersible tablets are developed1.

 

As per US FDA orodispersible tablets are defined as “a solid dosage form containing medicinal substance or active in gradient which disintegrate rapidly usually within a matter of seconds when placed up on a tongue2” Several techniques are developed to formulate fast dissolving tablets such are lyophilization, direct compression, sublimation, cotton candy process, molding, spray drying, mass extrusion, melt granulation3,4. Direct compression was selected for present investigation because of their cost effectiveness and simple processing.

Valsartan is an ACE inhibitor and effectively used in the treatment of hypertension5. It is used at a dose of 80 mg per day in the management of hypertension. It has very low bioavailability6.

With the view of above information an attempt were made to develop fast dissolving tablets of Valsartan by adopting Crospovidone as superdisintegrant. Formulation was developed by using different concentrations of Crospovidone and with different diluents to study the influence of concentration of disintegrant and diluent on rate of dissolution of Valsartan fast dissolving tablets.

 

MATERIALS AND METHODS:

Valsartan was obtained from Natco Pharma, Hyderabad, India. Crospovidone, spray dried lactose, Microcrystalline cellulose, talc and magnesium stearate were purchased from SD fine Chemicals Ltd, Mumbai. All other materials used were of analytical grade.

 

PREPARATION OF VALSARTAN FAST DISSOLVING TABLETS:

The compositions of the tablets are given in Tables 1. All the ingredients as shown in Table 1 were co-ground in a pestle and motor and then talc and magnesium stearate were added and mixed for 10 minutes. Compressed into tablets on a rotary multi-station tabletting machine (Cadmach Machinery Co. Pvt. Ltd., Mumbai) using 7 mm round and flat punches. Tablets were stored in airtight container and used for further study.

 

EVALUATION OF FORMULATED TABLET:

Hardness test:

The compression force required to break the tablet in to two halfs was measured. by using Monsanto hardness tester.

 

Weight variation:

Weight variation test is done with 20 tablets. It is the individual variation of tablet weight from the average weight of 20 tablets.

 

Friability7:

Roche friabilator was used to determine the friability. Pre weighed tablets were placed in friabilator and rotated at a speed of 25 rpm for 4 minutes or up to 100 revolutions. The tablets are dropped from a distance of 6 inches in each revolution. The tablets were then reweighed after removal of fines and the percentage of weight loss was calculated.

Content uniformity8:

Twenty tablets were powdered, and 10 mg equivalent weight of Valsartan in tablet powder was accurately weighed and transferred into a 100 ml volumetric flask. Initially, 5 ml methanol was added and shaken for 10 min. Then, the volume was made up to 100 ml with 6.8 phophate buffer. The solution in the volumetric flask was filtered, diluted suitably and analyzed spectrophotometrically at 250 nm.

 

Wetting time and water absorption ratio9:

A piece of paper folded twice was kept in a Petri dish containing 6 ml of purified water. A tablet having a small amount of Rosaline dye powder on the upper surface was placed on the tissue paper. The time required to develop a red colour on the upper surface of the tablet was recorded as the wetting time. The same procedure without Rosaline dye powder was followed for determining the water absorption ratio R was determined according to the following equation.

R = [(Wa – Wb)/Wb ]× 100

Where, Wb and Wa were the weights of the tablet before and after water absorption.

 

Disintegration test10:

The disintegration time for all formulations was carried out using tablet disintegration test apparatus. Six tablets were placed individually in each tube of disintegration test apparatus. The water was maintained at a temperature of 37°±2°C and time taken for the entire tablet to disintegrate completely was noted.

 

In vitro dispersion time11:

Tablet was added to 10 ml of phosphate buffer solution pH 6.8 (pH of saliva) at 37+/- 0.5°C. Time required for complete dispersion of tablet was measured.

 

In vitro dissolution studies:

In vitro dissolution studies are performed by using USP XXVI dissolution test apparatus using 6.8 phosphate buffer as dissolution medium. The paddles are allowed to rotate at speed of 50 rpm. The dissolution medium was maintained at a temperature of 37+0.5 OC and samples are withdrawn at constant interval. The volume of the withdrawn samples is replaced by fresh dissolution medium in order to keep the volume of the dissolution medium as constant. The withdrawn samples are filtered and absorbance was measured at absorption maxima of 250 nm using UV-visible spectrophotometer.

 

RESULTS AND DISCUSSIONS:

Four formulations were formulated with different concentrations of Crospovidone to study the influence of superdisintegrant concentration on rate of drug release from Valsartan fast dissolving tablets. Three formulations were formulated by Crospovidone 5% with three different diluents such are Mannitol, Spray dried lactose, Microcrystalline cellulose to study the influence of diluents on rate of drug release from the fast dissolving tablets of Valsartan. For each formulation blend of drug and excipient were evaluated for the micrometric properties. The powder blends are compressed by using direct compression. The micrometric properties indicate the all the formulations having god flow properties.

 

The tablets were evaluated for the various physical parameters such are weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time and in-vitro dispersion time (Table 2). Tablets are obtained with uniform weight due to uniform die fill, weight variation limits were with in the pharmacopeial specifications. The drug content was found in between 97.9 to 101.6 %. The hardness of the tablets between 3 to 4 kg/cm2. Friability of the tablet was below 1% indicating good mechanical strength. Wetting time and water absorption ratios are measured as the procedures described earlier. Wetting time and water absorption ratios were found in between 46 to 106 sec and 53 to 109 respectively. Wetting time is closely related to the inner structure of the tablet. This showed that wetting process was very rapid in almost all formulations. The disintegration time was ranges from 0.9 to 5.5 min. The disintegration time was found to be reduced as the concentration of the superdisintegrant was increased. The disintegration time was influenced by diluents also, the disintegration time was found to be less for the formulation made with spray dried lactose than compared with formulations made with Mannitol and Microcrystalline cellulose.

 

All the formulations follow first order kinetics and drug release profiles are shown in Figure 1 and 2. The dissolution kinetics of the Valsartan fast dissolving tablets were shown in Table 3. The dissolution rate was found to be more for the formulation made with 5% Crospovidone as superdisintegrant. The dissolution rate was found to be increased by increasing concentration of the superdisintegrant. The dissolution rate was found to be more for formulation made with spray dried lactose as a diluent than compared with Microcrystalline cellulose and Mannitol indicating rate of the dissolution was also influenced by the type of the diluent adopted.

 

Figure: 1 In vitro drug release profile for tablets formulated with different concentrations of Crospovidone

 

F1 formulated with 2% Crospovidone (♦),

F2 formulated with 3% Crospovidone (■),

F3 formulated with 4% Crospovidone (),

F4 formulated with 5% Crospovidone (-).


Table -1 Composition of ingredients for Valsartan fast dissolving tablets.

S. No

Ingredients

F1

F2

F3

F4

F5

F6

1

Valsartan

80

80

80

80

80

80

2

Crospovidone

4

6

8

10

10

10

3

Microcrystalline cellulose

112

110

108

106

-

-

4

Spray dried lactose

-

-

-

-

106

-

5

Mannitol

-

-

-

-

-

106

6

Talc

2

2

2

2

2

2

7

Mg striate

2

2

2

2

2

2

8

Total weight

200

200

200

200

200

200

 

Table -2 Physical parameters of Valsartan fast dissolving tablets.

S. No.

Parameters

F1

F2

F3

F4

F5

F6

1

Weight variation (%)

5.6

5.9

6

5.2

6.2

5

2

Drug content (%)

98.3

99.8

97.9

101.6

99

98.5

3

Disintegration time (min)

5.5

3.1

2.3

1.4

0.9

2.6

4

Friability (%)

0.82

0.87

0.73

0.86

0.6

0.78

5

Hardness (kg/sqcm)

3.5

3

4

4

3.5

4

6

Wetting time (sec)

106

84

58

50

46

52

7

Water absorption ratio

53

68

70

89

85

88

8

In-vitro dispersion time (min)

6.4

4.2

3.8

1.5

1.1

3.3

 

Table-3  In-vitro dissolution kinetics for Valsartan fast dissolving tablets

S. No.

Formulation

T 50

(min)

T 90

(min)

DE 15

(%)

K

(min-1)

Correlation coefficient values

Zero Order

First order

Hixsoncrowell Cube root

1

F1

5.7

19

59

0.121

0.71

0.97

0.93

2

F2

3.5

11.5

64.6

0.209

0.67

0.97

0.92

3

F3

2.4

7.9

70.3

0.293

0.70

0.96

0.94

4

F4

2.1

7

75.1

0.330

0.80

0.99

0.95

5

F5

1.8

6.1

76.5

0.365

0.82

0.98

0.95

6

F6

2.4

8

62.2

0.288

0.86

0.99

0.96

 


Figure: 2 In vitro drug release profile for tablets formulated with different diluents.

 

F4 formulated with Microcrystalline cellulose (♦),

F5 formulated with Spray dried lactose (),

F6 formulated with Mannitol (■),

 

CONCLUSION:

In the present research work it was concluded that the rate of dissolution was found to be increased by increasing the concentration of the Crospovidone, and the rate of dissolution was also influenced by type of the diluent adopted in the formulation. Spray dried lactose was found to be more suitable for Valsartan fast dissolving tablets than compared to Microcrystalline cellulose and Mannitol.

 

REFERENCE:

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2.        Suresh bandari. “Orodispersible tablets: An over view.Asian Journal of Pharmaceutics. 2008;1:1-5.

3.        Debjit Bhowmik, Chiranjib.B, Krishnakanth, Pankaj, R.Margret Chandira. “Fast Dissolving Tablet”: An Overview. Journal of Chemical and Pharmaceutical Research, 2009, 1(1): 163-177.

4.        Corveleyn S and Remon JP.“Formulation and production of rapidly disintegrating tablets by lyophilization using hydrochlorothiazide as a model drug”. Int J Pharm 1997; 152: 215-225.

5.        Leidig M, Bambauer R, Kirchertz EJ, Szabã T, Handrock R,Leinung D, et al. Efficacy, safety and tolerability of Valsartan 80 mg compared to irbesartan 150 mg in hypertensive patients on long-term hemodialysis. Clin Nephrol. 2008;69(6):425–32.

6.        http://www.drugbank.ca/drugs/DB00177

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8.        C.P. Jain and P.S. Naruka. “Formulation and evaluation of fast dissolving tablets of Valsartan”. International Journal of Pharmacy and Pharmaceutical Sciences, 2009;1(1): 219-227.

9.        Sunada H., Yonezawa Y., Danjo K., Otsuka A., Iida K., Preparation and evaluation of compressed tablet rapidly disintegrating in oral cavity. Chem. Pharm. Bull.s1996;44: 2121-2127.

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Received on 20.09.2010          Modified on 10.10.2010

Accepted on 24.10.2010         © RJPT All right reserved

Research J. Pharm. and Tech. 4(3): March 2011; Page 454-456