You are hereFORMULATION AND EVALUATION OF SUBLINGUAL TABLETS OF NIFEDIPINE

FORMULATION AND EVALUATION OF SUBLINGUAL TABLETS OF NIFEDIPINE


EVALUATION OF TABLETS:
The flow properties of blends (before compression) were characterized in terms of Angle of repose7, Bulk density and tapped density 8, Carr’s index9and Hausner’s ratio10 and evaluation of tablets can be divided into physical and chemical parameters. Physical appearance ,Tablet size and thickness, Average weight of tablets, Hardness test, and chemical parameters like content uniformity, in vitro dispersion time and in-vitro drug release.

Hardness: The crushing strength of the tablets was measured using a Monsanto hardness tester.          Three tablets from each formulation batch were tested randomly and the average reading was noted 11,12

Friability: Ten tablets were weighed and placed in a Roche friabilator (Veego, India). Twenty pre weighed tablets were rotated at 25 rpm for 4 min. The tablets were then de-dusted and reweighed and the percentage of weight loss was calculated. The percentage friability of the tablets was measured13.

Weight variation:Randomly, twenty tablets were selected after compression and the mean weight was determined. None of the tablets deviated from the average weight by more than ±10% 14.

Drug content:Ten tablets were randomly sampled from each formulation batch, finely powdered and individually estimated for the drug content after suitable dilution, using UV-VIS spectrophotometer (UV-1601, Shimadzu) at 235 nm after suitable dilution with distilled water 15. The mean percent drug content was calculated as an average of three determinations.

Wetting time:A piece of tissue paper (12cmx10.75cm)folded twice was placed in a Petri dish (Internal Diameter=9cm) containing 9ml of buffer solution simulating saliva pH 6.8, which had the following composition, NaCl (0.126g), KCl (0.964g), KSCN (0.189g),KH2PO4 (0.655g) and urea (0.200g) in 1Litre of distilled water. A tablet was placed on the paper and the time taken for complete wetting was noted 16. Three tablets from each formulation were randomly selected and the average wetting time was noted.

In vitro dispersion time: In vitro dispersion time was measured by dropping a tablet in a 10ml measuring cylinder containing 6ml of buffer solution simulating saliva fluid (pH 6.8) 17,18.

Dissolution study:In-vitro dissolution study was performed by using USP Type II Apparatus (Paddle type)[Veego Tablet Dissolution Tester] at 50 rpm. Phosphate buffer pH 6.8, 900 ml was used as dissolution medium which maintained at 37±0.5°C. Aliquot of dissolution medium (10 ml) was withdrawn at specific time intervals(2 min) and was filtered. The amount of drug dissolved was determined by UV spectrophotometer (Shimadzu,Japan) by measuring the absorbance of the sample at 235 nm 19.

RESULTS AND DISCUSSION:
Among the soluble diluents, mannitol was selected as a diluent considering its advantages in terms of easy availability and negative heat of dissolution.Table 2 shows us the granule properties of all the batches which are within the limits. Table 3 shows that all the formulated tablets exhibited low weight variation . The drug content of all the formulations was found to be between 98.52 - 101.67 % which was within the acceptable limits as per USP XXVII. The batches F2 and F3 were prepared using low concentrations of super disintegrants to study its effect on disintegration time. Batch F9 , containing 10% of both super disintegrants in their ratios, showed the least disintegrating time.  Tablets with lower friability (0.7%) may not break during handling on machines and/or shipping . In vitro release studies were carried out using USP XXIII tablet dissolution test apparatus paddle method at 37±0.5oC, taking 900 ml of dissolution medium. Speed of rotation of the paddle was set at 50 rpm. Sample of 10 ml were withdrawn after 1,2,3,4,5,6,7,8,9 min and analyzed spectrophotometrically at 235 nm. Formulation F9  prepared by wet granulation technique showed good release from final tablets showed release 99.85% drug  at the end of 9 min when compared to other batches. The in vitro dissolution profile (Fig.2) indicated faster and maximum drug release from formulation F9. Table 4 shows the wetting time and In-vitro dispersion time of all the batches and for F9 the values are 20 sec and 31 sec respectively.

REFERENCES:
1. Kamdar NM, Sonavane GS and Devarajan PV. Indian J Pharma Sci 2002; 64(3) 292- 293.
2.Laurence L Brunton, Goodman and Gilman’s: The Pharmacological Basis of Therapeutics, 10th Ed,McGraw- Hill, New York, 2001, 621-624.
3. Kuchekar BS and Arumugam V. Indian J Pharma Edu 2001; 35:150.
4. Croom, Katherine F, Wellington, Keri. Drugs 2006; 66(4): 497-528.
5. Richard D Howland, Mary J Mycek Lippincott’s Reviews pharmacology, 3rded. Philadelphia: Lippincott Williams and Wilkins; 1997,211.
6. Anthony J Trevor, Bertram G Katzung, Usan B Masters Katzung and Trevor’s Pharmacology, 7thed.Singapore: McGraw Hill medical publishing; 2005,110.8. Newman AW. Micromeritics: Britain HG; Physical Characterization of Pharmaceutical Solids. Marcel Dekker Inc, Newyork; Basel, 1995; 70; 271-275.
7. Newman AW. Micromeritics: Britain HG; Physical Characterization of Pharmaceutical Solids. Marcel Dekker Inc, Newyork; Basel, 1995; 70; 293-294.
8. Newman AW. Micromeritics: Britain HG; Physical Characterization of Pharmaceutical Solids. Marcel Dekker Inc, Newyork; Basel, 1995; 70; 271-275.
9. Wells J; Pharmaceutical Preformulation: Aulton ME; Pharmaceutics: The Science of dosage form design. 3rd edi, Edinburg, London, Melbourne, Newyork, 1998; 247.
10. Banker GS, Anderson NR; Tablets: Lachman L, Lieberman HA, Kanig JL; the Theory and Practice of Industrial Pharmacy. 3rd edi, Varghese Publication House, Bombay, 1987; 296-303
11. The official compendium of standards. The United States Pharmacopoeial Convention, 2007, USP 30,NF 25.
12. El-Arini Sk, Lenenberger H,Modelling of drug release from polymer matrices: Effect of drug loading, Int JPhar,1211915,141-148.
13.Indurwade NH, Rajyaguru TH and Nakhat PD. Indian Drugs 2002; 39(8): 405-09.
14.Bhaskaran S and Narmada GV. Indian Pharmacist 2002;1(2):9-12.
15. Bhagwati ST, Hiremath SN, Comparative evaluation of disintegrants by formulating cefixime dispersible tablets, Ind J Phar Edu Res, 39, 2005, 194-197.
16. Banker GS,Anderson NR, The theory and practice of Industrial Pharmacy,3rd Ed, Varghese Publishing House, 1987, 293-299.
17. Sweetman SC, Martindale; The complete drugreference,33rd Ed, Pharmaceutical Press, London,2002, 1235-1237.
18. Bi YX,Sinnada H,Yonezawa ,Evaluation of rapidly disintegrating tablets by direct compression method, Drug Dev Ind Phar,25,1999,571-581.
19.Shangraw R, Mitrevej A and Shah M. Pharma Tech 1980;4(10):49-57.

ACKNOWLEDGEMENTS:
We thank Venkata Balakrishna rao. N of Research and Development Department, Natco Pharma Limited, Kothur for his constant encouragement and support.

TABLE : 1 FORMULATION VARIABLES FOR NIFEDIPINE SUB-LINGUAL TABLETS:

INGREDIENTS (MG)

F1

F2

F3

F4

F5

F6

F7

F8

F9

Nifedipine

20

20

20

20

20

20

20

20

20

Crospovidone


12.50

5.00

7.5

8.5

5.00

8.5

5.00

14.5

12.50

Croscarmellose

Sodium

12.5

7.5

7.5

14.5

12.5

10.5

12.5

2.5

7.5

Aspartame

5

5

5

5

5

5

5

5

5

aerosil

1

1

1

1

1

1

1

1

1

Raspberry flavor

2

2

2

2

2

2

2

2

2

mannitol

144

156.5

154

146

151.5

150

151.5

152

149

Talc

3

3

3

3

3

3

3

3

3

TABLE 2: GRANULE PROPERTIES OF ALL THE BATCHES:

Formulation

Bulk density* (g/cm3)


Tapped density* (g/cm3)


Carr’s index* (IC)

Hausner’s ratio*

(HR)

Angle of repose*

(?)

F1

0.4111 ± 0.02

0.3701 ± 0.02

18.00 ±0.11

1.11 ± 0.01

21.55±0.11

F2

0.3152 ± 0.02

0.3038 ± 0.04

15.31 ±0.10

1.16 ± 0.02

23.22±0.15

F3

 0.4136 ± 0.05

0.3760 ± 0.01

18.76 ±0.11

1.12 ± 0.03

22.54±0.18

F4

0.3152 ± 0.01

0.4155 ± 0.02

16.13 ±0.06

1.21 ± 0.01

18.52±0.11

F5

0.3135 ± 0.02

0.4133 ± 0.03

17.10 ±0.06

1.19 ± 0.01

19.56±0.15

F6

0.4201 ± 0.02

0.3536 ± 0.02

18.05 ±0.02

1.11 ± 0.04

20.96±0.18

F7

0.3725±0.05


0.3589±0.04

16.56±0.13

1.25±0.03

18.96±0.15

F8

0.4104±0.04

0.3782±0.02

18.02±0.05

1.58±0.04

19.26±0.14

F9

0.4251±0.05

0.3598±0.05

18.15±0.02

1.08±0.05

17.58±0.11

TABLE 3: EVALUATIONS OF ALL BATCHES OF NIFEDIPINE TABLETS

Formulation

Average *weight

(mg) ± SD

Hardness*

(Kg/cm2)

± SD

Friability

(%)

DT* (sec.) ±

SD

Content

uniformity

% drug

release

F1

205.2±0.12

5.2±0.48

0.45

61±0.8

99.89

94.56

F2

202.5±0.48

4.5±0.52

0.58

98±0.5

100.51

78.65

F3

211.2±0.25

6.3±0.25

0.42

95±0.1

101.67

92.55

F4

209.5±0.89

6.5±0.55

0.65

65±0.5

98.52

89.56

F5

205.5±0.78

4.7±0.52

0.48

69±0.7

99.23

85.36

F6

206.5±0.63

5.6±0.85

0.59

71±0.2

99.62

86.52

F7

209.4±0.58

4.9±0.52

0.68

89±.0.7

99.65

83.55

F8

202.5±0.12

5.1±0.23

0.57

95±0.8

98.66

95.65

F9

203.8±0.65

4.6±0.56

0.45

56 ±0.4

99.98

99.85

*All reading are average + (SD)

TABLE 4: TABLE SHOWING WETTING TIME AND IN-VITRODISPERSION TIME.

PARAMETERS

F1

F2

F3

F4

F5

F6

F7

F8

F9

Wetting Time (sec)

15

86

62

51

68

65

72

40

20

In vitro dispersion time (sec)

22

92

68

64

72

78

82

55

31

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