Development and Evaluation of Gastroretentive Floating Tablets of Nizatidine based on Effervescent Technology

 

Dr. Y. Krishna Reddy*, Faria Tahseen

Department of Pharmaceutics, Nalanda College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad, Telangana.

*Corresponding Author E-mail: rajinisuralabs1@gmail.com

 

ABSTRACT:

In the present research work gastro retentive floating matrix formulation of Nizatidine by using various polymers were developed. Initially analytical method development was done for the drug molecule. Absorption maxima was determined based on that calibration curve was developed by using different concentrations. Gas generating agent sodium bicarbonate concentration was optimised. Then the formulation was developed by using different concentrations of polymers Amla extract, Ginger extract, Fenugreek extract, Isapgol husk as polymeric substances. The formulation blend was subjected to various preformualation studies, flow properties and all the formulations were found to be good indicating that the powder blend has good flow properties. Among all the formulations the formulations Amla extract as polymer were retarded the drug release more than12 hours (F3=98.73%). whereas in low concentrations the polymer was unable to produce the desired action. The optimised formulation dissolution data was subjected to release kinetics, from the release kinetics data it was evident that the formulation followed peppas release kinetics mechanism of drug release.

 

KEYWORDS: Nizatidine, Amla extract, Ginger extract, Fenugreek extract, Isapgol husk, Floating Tablets.

 

 

INTRODUCTION:

Oral delivery of drugs is the most preferable route of drug delivery. Oral route is considered most natural, uncomplicated, convenient and safe due to its ease of administration, patient compliance and flexibility in formulation and cost effective manufacturing process1.

 

Rapid gastrointestinal transit could result in incomplete drug release from the dosage form above the absorption zone leading to diminished efficacy of the administered dose. These considerate have led to the development of a controlled or sustained delivery system.

 

The main purpose for developing these systems was to release the drug slowly into the gastrointestinal tract (GIT) and maintain an effective drug concentration in the systemic circulation for long time. Gastroretentive drug delivery is an approach to prolong gastric retention time, thereby targeting site – specific drug release in the upper GIT for local and systemic effect. Therefore, different approaches have been proposed to retain the dosage form in the stomach. These include bioadhesive systems, swelling and expanding systems and floating systems. Floating drug delivery or hydrodynamically balanced systems have a sufficient buoyancy to float over the gastric contents and remain buoyant in the stomach without affecting the gastric emptying rate for a prolong period2-5.

 

Nizatidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer and gastroesophageal reflux. Its recommended dose is either 300mg once daily at bedtime or 150mg twice daily6. Nizatidine has short biological half life (1-2 hours) and susceptible to metabolism by colonic bacteria7. It has been reported that the local delivery of H2-receptor antagonists increases the stomach wall receptor site bioavailability and increases efficacy of these drugs to reduce acid secretion8. Based on the criteria, nizatidine is a suitable candidate for gastroretentive drug delivery system.

 

MATERIALS:

Nizatidine gift sample provided by Sura Labs, Dilsukhnagar, Hyderabad. Amla extract, Ginger extract, Fenugreek extract, Isapgol husk, Sodium bicarbonate, Magnesium Stearate, MCC pH102, Talc purchased from Merck Specialities Pvt Ltd, Mumbai, India.

 

METHODS:

Preformulation parameters:

It was evaluated for Bulk density, True density, Angle of repose, Compressibility index, Hausner ratio.

 

Evaluation of post compression parameters for prepared Tablets:

The designed formulation tablets were studied for their physicochemical properties like weight variation, hardness, thickness, friability and drug content.

 

In vitro Buoyancy studies:

The in vitro buoyancy was determined by floating lag time, and total floating time. The tablets were placed in a 100ml beaker containing 0.1N HCL. The time required for the tablet to rise to the surface and float was determined as floating lag time (FLT) and duration of time the tablet constantly floats on the dissolution medium was noted as Total Floating Time respectively (TFT).

 

In vitro drug release studies:

900ml 0f 0.1 HCL was placed in vessel and the USP apparatus –II (Paddle Method) was assembled. The medium was allowed in the vessel was covered the apparatus was operated for 12 hours and then the medium 0.1 N HCL was taken and process was continued from 0 to 12 hrs at 50 rpm. At definite time intervals of 5 ml of the receptors fluid was withdrawn, filtered and again 5ml receptor fluid was replaced. Suitable dilutions were done with media and analyzed by spectrophotometrically.

 

Application of Release Rate Kinetics to Dissolution Data:

To analyze the mechanism of the drug release rate kinetics, the obtained data were fitted into zero-order, first order, Higuchi and Korsmeyer-Peppas release model.

 

Formulation development of Tablets:

All the formulations were prepared by direct compression.

Table No:1 Formulation composition for tablets

INGREDIENTS

FORMULATION CHART

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12

Nizatidine

75

75

75

75

75

75

75

75

75

75

75

75

Amla extract

20

30

40

-

-

-

-

-

-

-

-

-

Ginger extract

-

-

-

20

30

40

-

-

-

-

-

-

Fenugreek extract

-

-

-

-

-

-

20

30

40

-

-

-

Isapgol husk

-

-

-

-

-

-

-

-

-

20

30

40

Sodium bicarbonate

10

10

10

10

10

10

10

10

10

10

10

10

Talc

5

5

5

5

5

5

5

5

5

5

5

5

Magnesium stearate

4

4

4

4

4

4

4

4

4

4

4

4

MCC

86

76

66

86

76

66

86

76

66

86

76

66

Total tablet weight

200

200

200

200

200

200

200

200

200

200

200

200

All the quantities were in mg

 

RESULTS AND DISCUSSION:

 

Table No:2 Preformulation parameters of powder blend

Formulation Code

Angle of Repose

Bulk density (gm/mL)

Tapped density

(gm/mL)

Carr’s index

(%)

Hausner’s Ratio

F1

34.35±0.39

0.51±0.01

0.64±0.02

20.31±0.02

1.25±0.02

F2

34.49±0.58

0.50±0.01

0.63±0.02

19.04±0.01

1.26±0.01

F3

34.65±0.50

0.49±0.02

0.60±0.01

18.33±0.08

1.22±0.04

F4

33.82±0.53

0.52±0.02

0.63±0.01

17.46±0.01

1.21±0.01

F5

34.45±0.24

0.50±0.01

0.61±0.01

18.03±0.01

1.22±0.02

F6

32.93±0.47

0.53±0.01

0.63±0.02

15.87±0.02

1.18±0.02

F7

33.33±0.21

0.50±0.01

0.62±0.02

19.35±0.01

1.24±0.01

F8

33.60±0.58

0.49±0.01

0.63±0.02

22.22±0.02

1.28±0.01

F9

33.80±0.55

0.51±0.01

0.64±0.01

20.31±0.01

1.25±0.03

F10

34.48±0.56

0.50±0.01

0.65±0.01

23.07±0.01

1.30±0.02

F11

33.93±0.50

0.50±0.02

0.64±0.03

21.87±0.02

1.28±0.02

F12

34.14±0.71

0.49±0.03

0.64±0.04

23.43±0.03

1.30±0.01

Quality Control Parameters For tablets:

Table No:3 In vitro quality control parameters for tablets

Formulation codes

Average Weight (mg)

Hardness (kg/cm2)

Friability (%loss)

Thickness (mm)

Drug content (%)

Floating lag time (min)

Total Floating Time (Hrs)

F1

198.5

3.6

0.25

3.98

97.69

3.9

6

F2

199.2

3.9

0.61

3.86

98.24

3.8

3

F3

197.8

3.4

0.34

3.19

99.28

2.9

7

F4

198.1

3.1

0.42

3.75

96.19

3.1

5

F5

199.0

3.8

0.19

3.68

95.42

2.6

6

F6

196.4

3.7

0.56

3.49

98.34

3.4

8

F7

200.0

3.4

0.64

3.67

97.42

2.7

5

F8

198.4

3.2

0.72

3.11

100.0

3.4

8

F9

199.7

3.7

0.39

3.29

95.99

2.8

9

F10

197.3

3.8

0.47

3.67

98.19

3.0

6

F11

198.4

3.9

0.58

3.49

96.48

2.9

7

F12

199.9

3.2

0.61

3.42

99.12

2.7

9

All the parameters for tablets such as weight variation, friability, hardness, thickness, drug content were found to be within limits.

 

In Vitro Drug Release Studies:

Table No:4 In vitro dissolution data

Time (hr)

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12

0

0

0

0

0

0

0

0

0

0

0

0

0

0.5

7.3

10.38

11.49

12.72

13.34

8.19

11.85

13.83

10.74

21.62

19.41

25.87

1

10.68

14.72

15.85

25.74

18.97

16.75

15.35

18.72

18.42

35.41

23.99

28.19

2

16.24

23.84

24.57

36.22

26.19

22.95

20.84

23.47

24.53

47.44

31.82

34.67

3

21.29

34.12

34.88

48.97

32.99

27.39

26.35

26.81

30.14

56.26

38.06

41.81

4

26.74

45.03

45.80

52.62

38.49

32.98

36.54

31.77

35.44

65.46

46.12

46.37

5

34.95

56.06

56.42

59.78

45.18

39.47

45.35

39.06

46.35

71.19

49.20

52.92

6

41.67

62.17

60.19

63.99

53.75

48.12

50.95

45.53

52.94

79.55

53.81

58.48

7

58.48

69.85

65.96

69.11

58.67

53.62

54.84

49.77

59.47

83.93

62.24

64.72

8

73.75

74.92

71.27

73.15

63.18

57.24

61.56

53.47

64.82

89.72

68.71

67.49

9

79.38

79.56

75.48

78.24

69.87

66.11

66.68

62.18

69.71

93.18

73.82

74.82

10

86.25

83.69

81.15

83.91

74.51

69.44

75.91

68.51

73.28

97.86

79.28

80.97

11

90.11

97.01

86.96

86.11

86.10

73.82

83.19

73.87

77.92

 

85.31

86.88

12

94.39

 

98.73

91.42

96.49

80.19

96.87

89.15

81.42

 

90.87

95.17

 

 

Fig No:1 Dissolution data of Nizatidine Floating tablets containing Amla extract, Ginger extract, Fenugreek extract and Isapgol husk.

 

From the dissolution data it was evident that the formulations prepared with Amla extract as polymer were retarded the drug release more than 12 hours.

 

Whereas the formulations prepared with Low concentration of Ginger extract retarded the drug release up to 12 hours in the concentration 30 mg. In higher concentrations the polymer was unable to retard the drug release.

 

Whereas the formulations prepared with low concentration of Fenugreek extract retarded the drug release up to 12 hours in the concentration 20 mg. In higher concentrations the polymer was unable to retard the drug release.

 

Whereas the formulations prepared with higher concentration of Isapgol husk extract retarded the drug release up to 12 hours in the concentration 40 mg. In lower concentrations the polymer was unable to retard the drug release.

 

Hence from the above dissolution data it was concluded that F3 formulation was considered as optimised formulation because good drug release (98.73 %) in 12 hours.

 

Application of Release Rate Kinetics to Dissolution Data for optimised formulation:

Table No:5 Application kinetics for optimised formulation

Cumulative (%)

Release Q

Time (T)

Root (T)

Log

(%) Release

Log (T)

Log (%) Remain

Release Rate (Cumulative % Release / t)

1/Cum% Release

Peppas log Q/100

% Drug Remaining

Q

01/3

Qt

1/3

Q

01/3-Qt1/3

0

0

0

 

 

2.000

 

 

 

100

4.642

4.642

0.000

11.49

0.5

0.707

1.060

-0.301

1.947

22.980

0.0870

-0.940

88.51

4.642

4.457

0.185

15.85

1

1.000

1.200

0.000

1.925

15.850

0.0631

-0.800

84.15

4.642

4.382

0.259

24.57

2

1.414

1.390

0.301

1.878

12.285

0.0407

-0.610

75.43

4.642

4.225

0.416

34.88

3

1.732

1.543

0.477

1.814

11.627

0.0287

-0.457

65.12

4.642

4.023

0.618

45.8

4

2.000

1.661

0.602

1.734

11.450

0.0218

-0.339

54.2

4.642

3.784

0.857

56.42

5

2.236

1.751

0.699

1.639

11.284

0.0177

-0.249

43.58

4.642

3.519

1.123

60.19

6

2.449

1.780

0.778

1.600

10.032

0.0166

-0.220

39.81

4.642

3.415

1.227

65.96

7

2.646

1.819

0.845

1.532

9.423

0.0152

-0.181

34.04

4.642

3.241

1.401

71.27

8

2.828

1.853

0.903

1.458

8.909

0.0140

-0.147

28.73

4.642

3.063

1.579

75.48

9

3.000

1.878

0.954

1.390

8.387

0.0132

-0.122

24.52

4.642

2.905

1.736

81.15

10

3.162

1.909

1.000

1.275

8.115

0.0123

-0.091

18.85

4.642

2.661

1.980

86.96

11

3.317

1.939

1.041

1.115

7.905

0.0115

-0.061

13.04

4.642

2.354

2.288

98.73

12

3.464

1.994

1.079

0.104

8.228

0.0101

-0.006

1.27

4.642

1.083

3.559

 

Fig No:2 Zero order release kinetics

 

 

Fig No:3 Higuchi release kinetics

 

Fig No:4 Kors mayer peppas release kinetics

 

 

Fig No:5 First order release kinetic

Optimised formulation F3 was kept for release kinetic studies. From the above graphs it was evident that the formulation F3 was followed peppas release kinetics.

 

АCKNOWLEDGEMENT:

Thе authors arе thankful to Sura Labs, Dilshukhnagar, Hyderabad for providing thе nеcеssary facilitiеs, Materials for thе rеsеarch work.

 

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Received on 27.02.2020         Modified on 20.03.2020

Accepted on 23.04.2020     ©AandV Publications All right reserved

Res.  J. Pharma. Dosage Forms and Tech.2020; 12(2): 93-97.

DOI: 10.5958/0975-4377.2020.00017.8