Extended Release Matrix Tablets of Nateglinide: Formulation and In vitro Evaluation

 

Dr. Y. Krishna Reddy*, K. Akhila

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

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

 

ABSTRACT:

In the present study to establish oral extended release tablets of Nateglinide using different polymers. The tablets were prepared using Xanthan gum, HPMC K15, Carbapol 934 using different polymers to impart extended release study. Tablets were evaluated by different parameters such as weight variation, content uniformity, thickness, hardness, IR spectral analysis, in vitro release studies and kinetic analysis of dissolution data. The present study concluded that extended release tablets of Nateglinde can be a good way to increases the dissolution and bioavailability of Nateglinde.

 

KEYWORDS: Nateglinde, Extended release tablets.

 

 

 

INTRODUCTION:

Oral drug delivery is the largest and oldest segment of the total drug delivery market. It is the fastest growing and most preferred route for drug administration. Use of hydrophilic matrices for oral extended release of drugs is common practice in the pharmaceutical industry. However, also drugs with long half-life qualify if a reduction in steady state fluctuation is desired.

 

With many drugs, the basic goal of therapy is to achieve a steady-state blood level or tissue level that is therapeutically effective and non toxic for an extended period of time. To achieve better therapeutic action various types of drug delivery systems are available, out of which extended release systems are gaining much importance because of their wide advantages over others like ease of administration, convenience and non-invasiveness1.

 

Nateglinide is highly tissue selective with low affinity for heart and skeletal muscle. The drug is widely used for the management of type-2 diabetes. It has short biological half life (1.5 ± 0.7 h) and bioavailability is 73%. Moreover, site of absorption of Nateglinide is in the intestine. The common goal for increased duration is twice a day, or when feasible, once a day. Several properties of the drug itself can lead to the achievement of a 12 to 24 hours oral prolonged release dosage form. Some of the characteristics militating against success are very short half life or a relatively large single dose; potent drug with a low margin safety; poorly soluble drug, large first pass metabolism. The short biological half life of the drug favors the development of extended release formulation2-8.

 

MATERIALS:

Nateglinide gift sample provided by Sura Labs, Dilsukhnagar, Hyderabad. Xanthan gum, HPMC K15, Carbapol 934, PVP K30, Talc, Magnesium Stearate, MCCpH102 purchased from Merck Specialities Pvt Ltd, Mumbai, India.

 

 

 

Formulation development of Tablets:

All the formulations were prepared by direct compression.

 

Table No:1 Formulation composition for tablets

Ingrediants

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12

Nateglinide

60

60

60

60

60

60

60

60

60

60

60

60

Xanthan gum

20

40

60

80

-

-

-

-

-

-

-

-

HPMC K15

-

-

-

-

20

40

60

80

-

-

-

-

Carbapol 934

-

-

-

--

-

-

-

-

20

40

60

80

PVP K30

5

5

5

5

5

5

5

5

5

5

5

5

Talc

3

3

3

3

3

3

3

3

3

3

3

3

Magnesium Stearate

3

3

3

3

3

3

3

3

3

3

3

3

MCC pH 102

109

89

69

49

109

89

69

49

109

89

69

49

Total weight

200

200

200

200

200

200

200

200

200

200

200

200

All the quantities were in mg

 

 

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 drug release studies:

Dissolution parameters:  

Apparatus --USP-II, Paddle Method

Dissolution Medium-- 0.1 N HCl, pH 6.8 Phosphate buffer

RPM-- 50

Sampling intervals (hrs)--  

0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12

Temperature---37°C ± 0.5°C

 

Application of Release Rate Kinetics to Dissolution Data:

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

 

 

 

RESULTS AND DISCUSSION:

Preformulation parameters of powder blend

 

Table No:2 Pre-formulation parameters of Core blend

Formulation Code

Angle of Repose

Bulk density (gm/ml)

Tapped density (gm/ml)

Carr’s index (%)

Hausner’s Ratio

F1

25.0

0.719

0.789

22.2

1.28

F2

21.0

0.658

0.726

15.4

1.08

F3

20.0

0.621

0.776

9.92

1.11

F4

23.0

0.624

0.712

12.78

1.14

F5

22.0

0.677

0.722

9.14

1.10

F6

21.0

0.656

0.778

12.98

1.14

F7

23.0

0.621

0.723

13.69

1.15

F8

22.0

0.699

0.744

16.53

1.19

F9

20.0

0.668

0.734

10.34

1.11

F10

25.0

0.614

0.854

15.80

1.18

F11

21.0

0.658

0.726

15.4

1.08

F12

25.0

0.719

0.789

22.2

1.28

 

 

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 (%)

F1

199

3.57

0.29

2.29

99

F2

200

3.27

0.21

2.22

100

F3

198

3.33

0.36

2.46

98

F4

198

3.45

0.49

2.38

99

F5

197

3.49

0.35

2.76

98

F6

200

3.38

0.47

2.43

97

F7

199

3.42

0.54

2.37

99

F8

198

3.55

0.28

2.35

98

F9

195

3.62

0.36

2.28

99

F10

196

3.46

0.55

2.45

97

F11

199

3.38

0.44

2.54

97

F12

197

3.31

0.53

2.39

98

 

In Vitro Drug Release Studies

Table No:4 Dissolution Data of Nateglinide Tablets

TIME (HRS)

CUMULATIVE percent drug RELEASED

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

18.25

12.47

8.52

5.14

24.51

17.14

13.12

9.56

39.62

26.37

22.34

19.54

 

1

27.55

19.56

12.14

11.62

31.53

23.27

18.56

12.62

55.61

37.36

32.54

25.51

 

2

48.44

28.78

18.02

16.14

39.64

32.66

23.34

19.42

73.01

46.08

41.08

31.65

 

3

68.62

34.43

24.61

21.41

46.16

41.84

26.85

25.83

89.62

59.52

46.52

42.47

 

4

73.75

41.54

29.41

25.15

61.31

54.64

33.87

29.35

98.11

66.33

59.42

46.26

 

5

81.63

49.16

35.47

31.56

76.64

61.54

41.53

35.88

 

76.14

67.57

52.33

 

6

97.87

57.56

42.11

36.58

88.64

67.64

49.22

41.54

 

85.48

72.43

61.51

 

7

 

61.73

48.78

43.16

98.54

72.85

57.94

51.72

 

98.23

76.25

68.84

 

8

 

70.59

54.51

51.51

 

88.23

66.73

57.65

 

 

88.19

77.54

 

9

 

78.48

59.92

57.64

 

98.54

75.53

65.62

 

 

98.25

84.46

 

10

 

84.25

66.14

62.20

 

 

86.93

73.56

 

 

 

98.14

 

11

 

90.56

74.64

69.51

 

 

91.58

82.23

 

 

 

 

 

12

 

99.57

81.51

76.51

 

 

97.27

89.72

 

 

 

 

 

 

 

 

Fig No:1 Dissolution profile of Nateglinide (F1-F12 formulations)

 

Formulations prepared with Xanthan gum retarded the drug release in the concentration of 40 mg (F2 Formulation) showed required release pattern i.e., retarded the drug release up to 12 hours and showed maximum of 99.57% in 12 hours with good retardation. From the dissolution data it was evident that the formulations prepared with HPMC K15 as polymer were retard the drug release up to desired time period i.e., 12 hours. The formulations prepared with Carbapol 934 were unable to retard up to 12 hours. Hence they were not considered.

 

 

 

 

 

Application of Release Rate Kinetics to Dissolution Data:

 

Table No:5 Release kinetics data 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

0

0

0

 

 

2.000

 

 

 

100

12.47

0.5

0.707

1.096

-0.301

1.942

24.940

0.0802

-0.904

87.53

19.56

1

1.000

1.291

0.000

1.905

19.560

0.0511

-0.709

80.44

28.78

2

1.414

1.459

0.301

1.853

14.390

0.0347

-0.541

71.22

34.43

3

1.732

1.537

0.477

1.817

11.477

0.0290

-0.463

65.57

41.54

4

2.000

1.618

0.602

1.767

10.385

0.0241

-0.382

58.46

49.16

5

2.236

1.692

0.699

1.706

9.832

0.0203

-0.308

50.84

57.56

6

2.449

1.760

0.778

1.628

9.593

0.0174

-0.240

42.44

61.73

7

2.646

1.790

0.845

1.583

8.819

0.0162

-0.210

38.27

70.59

8

2.828

1.849

0.903

1.468

8.824

0.0142

-0.151

29.41

78.48

9

3.000

1.895

0.954

1.333

8.720

0.0127

-0.105

21.52

84.25

10

3.162

1.926

1.000

1.197

8.425

0.0119

-0.074

15.75

90.56

11

3.317

1.957

1.041

0.975

8.233

0.0110

-0.043

9.44

99.57

12

3.464

1.998

1.079

-0.367

8.298

0.0100

-0.002

0.43

 

 

 

Fig No:2 Zero order release kinetics graph

 

 

Fig No:3 Higuchi release kinetics graph

 

 

Fig No:4 Kars mayer peppas graph

 

Fig No:5 First order release kinetics graph

 

From the above graphs it was evident that the formulation F2 was followed Kors mayer peppas kinetics.

 

АCKNOWLEDGEMENT:

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

 

REFERENCES:

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2.        www.drugbank.ca/drugs 

3.        wikipedia.org/wiki/Nateglinide

4.        Milo Gibaldi, Donald Pferzier. Pharmacokinetics Edn 2, Vol.15 revised and expanded pp.185.

5.        Mr. Samir J. Shah, Dr. Paresh B. Shah Dr. Mukesh S. Patel, Dr. Mukesh R. Patel. A review on extended release drug delivery system and multiparticulate system. Vol 4, Issue 08, 2015.

6.        Wani MS. Controlled Release System A Review; Pharmaceutical Reviews., 2008; 6(1): 41-46.

7.        Brahmankar H A, Jaiswal S B. Bio pharmaceutics and pharmacokinetics. Treatise: Vallabh Prakashan; 2000.

8.        Priya V Bhosale, Arati N Ranade, Chandrakant Awahad. Formulation and Evaluation of Extended Release Tablet of Ranolazine. July - September 2015.

 

 

 

Received on 26.02.2020            Modified on 28.03.2020

Accepted on 18.04.2020  ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Res. 2020; 10(2):101-104.

DOI: 10.5958/2231-5691.2020.00019.2