Preparation and In vitro Characterisation Venlafaxine HCl Controlled Release Tablets

 

Dr. Y. Krishna Reddy*, K. Giri

 

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

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

 

ABSTRACT:

The aim of the present study was to develop Controlled release formulation of Venlafaxine HCL   to maintain constant therapeutic levels of the drug for over 12 hrs. Eudragit S 100, HPMC K4 M and HPMC K15 M were employed as polymers. All the formulations were prepared by direct compression method. The blend of all the formulations showed good flow properties such as angle of repose, bulk density, tapped density. The prepared tablets were shown good post compression parameters and they passed all the quality control evaluation parameters as per I.P limits. Whereas from the dissolution studies it was evident that the formulation (F5) showed better and desired drug release pattern i.e., 98.46 % in 12 hours. It contains the synthetic polymer HPMC K4 M as controlled release material. It followed zero order release kinetics mechanism.

 

KEYWORDS: Venlafaxine HCL, Eudragit S 100, HPMC K4 M, K15 M, Controlled release tablets.

 

 

 

INTRODUCTION:

Controlled release dosage form is a dosage form that release one or more drugs continuously in predetermined pattern for a fixed period of time, either systemically or locally to specified target organ. Greater attention is paid on development of oral controlled release drug delivery systems due to flexibility in designing of dosage form. The main challenges to oral drug delivery systems are to deliver a drug at therapeutically effective rate to desirable site, modulation of GI transit time and minimization of first pass elimination. Control release dosage form provides better maintenance of optimal and effective drug level for prolonged duration with less dosing frequency and side effects1,2. Venlafaxine HCL is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class.

 

This means it increases the concentrations of the neurotransmitters serotonin and norepinephrine in the body and the brain. Venlafaxine is used primarily for the treatment of depression, general anxiety disorder, social phobia, panic disorder, and vasomotor symptoms3-8.

 

The objective of the study includes to improve the bioavailability, Reduce the number of doses and to increase patient compliance it was formulated as controlled release tablets using various polymers9-10.

 

Materials:

Venlafaxine HCL gift sample provided by Sura Labs, Dilsukhnagar, Hyderabad. Eudragit S 100, HPMC K4 M, HPMC K15, PVP K30, Talc, Magnesium Stearate, MCC pH102 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.

 

Formulation development of Tablets:

All the formulations were prepared by direct compression.

Table No:1 Formulation composition for tablets

INGREDIENTS

FORMULATION CODE

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12

 

Venlafaxine HCL

37.5

37.5

37.5

37.5

37.5

37.5

37.5

37.5

37.5

37.5

37.5

37.5

 

Eudragit S 100

10

20

30

40

-

-

-

-

-

-

-

-

 

HPMC K4 M

-

-

-

-

10

20

30

40

-

-

-

-

 

HPMC K15 M

-

-

-

-

-

-

-

-

10

20

30

40

 

PVP K30

5

5

5

5

5

5

5

5

5

5

5

5

 

Magnesium stearate

3

3

3

3

3

3

3

3

3

3

3

3

 

Talc

5

5

5

5

5

5

5

5

5

5

5

5

 

MCC

139.5

129.5

119.5

109.5

139.5

129.5

119.5

109.5

139.5

129.5

119.5

109.5

 

Total weight

200

200

200

200

200

200

200

200

200

200

200

200

 

All the quantities were in mg

 

 

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:

900ml 0f 0.1 HCL was placed in vessel and the USP apparatus –II (Paddle Method) was assembled. The medium was allowed to equilibrate to temp of 37°C+ 0.5°C. Tablet was placed in the vessel and apparatus was operated for 2 hours and then the media 0.1 N HCL was removed and pH 6.8 phosphate buffer was added process was continued from upto 12 hrs at 50rpm. At definite time intervals withdrawn 5ml of sample, filtered and again 5ml media was replaced.  Suitable dilutions were done with media 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.

 

 

RESULTS AND DISCUSSION:

Table No:2 Preformulation parameters of powder blend

Formulations

Bulk Density(gm/cm2)

Tap Density (gm/cm2)

Carr’s Index (%)

Hausner ratio

Angle of Repose (Ɵ)

F1

0.55±0.001

0.62±0.005

11.29±0.10

1.13±0.011

23.31±0.14

F2

0.57±0.003

0.64±0.003

10.94±0.07

1.12±0.007

29.39±0.20

F3

0.59±0.004

0.69±0.004

11.94±0.09

1.14±0.011

27.55±0.13

F4

0.61±0.004

0.72±0.005

15.28±0.28

1.18±0.010

25.45±0.13

F5

0.52±0.003

0.58±0.002

10.34±0.09

1.12±0.009

29.56±0.24

F6

0.46±0.002

0.53±0.002

13.21±0.11

1.15±0.011

28.15±0.22

F7

0.57±0.004

0.63±0.003

9.52±0.050

1.11±0.010

29.56±0.23

F8

0.60±0.006

0.65±0.005

10.45±0.08

1.12±0.010

28.45±0.07

F9

0.47±0.003

0.52±0.002

14.55±0.12

1.17±0.007

25.45±0.16

F10

0.51±0.003

0.59±0.004

13.56±0.09

1.16±0.010

27.78±0.26

F11

0.63±0.004

0.70±0.001

12.50±0.10

1.14±0.008

26.67±0.23

F12

0.55±0.002

0.64±0.004

14.06±0.11

1.16±0.009

25.25±0.13

 

Quality Control Parameters For tablets:

Table No:3 In vitro quality control parameters for tablets

Formulation

Average weight(mg)

Hardness (kg/cm2)

Thickness (mm)

Friability (%)

Assay (%)

F1

198.2

5.3

3.15

0.14

98.15

F2

195.6

5.6

3.62

0.36

97.62

F3

199.1

5.9

3.85

0.58

99.31

F4

197.4

5.0

3.19

0.18

95.28

F5

198.5

5.9

3.75

0.62

98.35

F6

199.6

5.2

3.82

0.22

97.15

F7

195.3

5.8

3.31

0.15

99.75

F8

199.0

5.4

3.54

0.51

98.64

F9

198.9

5.1

3.81

0.49

99.11

F10

199.5

5.2

3.14

0.17

96.18

F11

200.0

5.7

3.25

0.52

99.59

F12

197.7

5.4

3.86

0.31

98.81

 

 

In Vitro Drug Release Studies:

Table No:4 In vitro dissolution data

Time (Hrs)

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

8.74

9.53

6.27

8.17

7.25

12.92

18.31

19.66

14.92

17.23

13.45

17.25

1

16.97

15.21

14.32

11.74

12.16

25.27

23.14

25.98

27.74

22.35

25.72

26.34

2

29.95

28.76

26.47

26.72

18.91

35.32

28.55

36.57

36.42

31.79

35.95

34.27

3

37.62

39.53

36.13

32.29

22.94

42.71

35.94

45.74

43.3

36.92

43.17

43.59

4

45.87

46.44

48.27

39.31

28.48

56.19

38.39

51.82

54.12

47.36

51.43

52.04

5

52.75

57.96

59.51

48.94

36.12

62.83

41.67

64.73

59.63

56.82

55.16

57.6

6

60.32

62.78

72.97

53.83

44.82

67.84

45.32

69.57

66.36

62.72

59.14

64.82

7

73.74

74.31

77.02

59.65

60.57

72.27

48.12

76.43

71.93

67.19

65.42

68.44

8

87.48

79.63

84.44

66.98

67.28

75.42

52.75

81.67

78.63

73.86

67.99

71.89

9

96.64

82.41

89.53

74.23

75.91

79.39

67.18

94.81

86.36

77.96

73.21

78.38

10

98.21

92.62

97.12

81.47

78.61

82.22

72.69

98.01

91.73

83.61

76.92

82.49

11

96.11

87.93

87.63

95.76

87.19

95.11

88.73

81.71

97.31

12

92.02

98.46

92.14

96.13

92.75

86.49

 

 

 

Fig No:1 Dissolution profile of All formulations prepared with HPMC K 100, Locust Bean gum and Karaya gum as polymer’s

 

From the above results it was evident that the formulation F5 is best formulation with desired drug release pattern extended up to 12 hours.

 

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

Q01/3

Qt1/3

Q01/3-Qt1/3

0

0

0

 

 

2.000

 

 

 

100

4.642

4.642

0.000

7.25

0.5

0.707

0.860

-0.301

1.967

14.500

0.1379

-1.140

92.75

4.642

4.527

0.115

12.16

1

1.000

1.085

0.000

1.944

12.160

0.0822

-0.915

87.84

4.642

4.445

0.196

18.91

2

1.414

1.277

0.301

1.909

9.455

0.0529

-0.723

81.09

4.642

4.328

0.313

22.94

3

1.732

1.361

0.477

1.887

7.647

0.0436

-0.639

77.06

4.642

4.255

0.386

28.48

4

2.000

1.455

0.602

1.854

7.120

0.0351

-0.545

71.52

4.642

4.151

0.491

36.12

5

2.236

1.558

0.699

1.805

7.224

0.0277

-0.442

63.88

4.642

3.997

0.644

44.82

6

2.449

1.651

0.778

1.742

7.470

0.0223

-0.349

55.18

4.642

3.807

0.834

60.57

7

2.646

1.782

0.845

1.596

8.653

0.0165

-0.218

39.43

4.642

3.404

1.238

67.28

8

2.828

1.828

0.903

1.515

8.410

0.0149

-0.172

32.72

4.642

3.198

1.443

75.91

9

3.000

1.880

0.954

1.382

8.434

0.0132

-0.120

24.09

4.642

2.888

1.753

78.61

10

3.162

1.895

1.000

1.330

7.861

0.0127

-0.105

21.39

4.642

2.776

1.866

87.63

11

3.317

1.943

1.041

1.092

7.966

0.0114

-0.057

12.37

4.642

2.313

2.329

98.46

12

3.464

1.993

1.079

0.188

8.205

0.0102

-0.007

1.54

4.642

1.155

3.487

 

 

 

 

 

 

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 F5 was followed Zero order release mechanism.

 

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 26.02.2020            Modified on  20.03.2020           

Accepted on 11.04.2020   ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech. 2020; 10(2):81-84.

DOI: 10.5958/2231-5713.2020.00015.X