Formulation and In Vitro Characterisation Oxcarbazepine Controlled Release Tablets

 

Sk. Asha Begum1*, B. Bhargavi2, J. Divya3, K. Swetha4, Sk. Zareena5, Lohitha S6, Ramya Sri S7

1,2,3,4,5,6Nimra College of Pharmacy, Ibrahimpatnam, Krishna District, Andhra Pradesh

7Department of Pharmaceutics, University of Technology, Osmania University, Hyderabad, Telangana

*Corresponding Author E-mail: ramyasuralabs1@gmail.com

 

ABSTRACT:

In the present work, an attempt has been made to develop controlled release tablets of oxcarbazepine by selecting of HPMC and Poly ethylene oxide as retarding polymers. All the formulations were prepared by direct compression method. The blend of all the formulations showed god 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. Among all the formulations F10 formulation showed maximum % drug release i.e., 98.84 % in 12 hours hence it is considered as optimized formulation F10 which contains Ethylcellulose N50 (20 mg) . Whereas the formulations with HPMC K15M showed more retarding with increasing concentration of polymer. The formulations with Poly ethylene oxide were unable to produce the desired drug release pattern.

 

KEYWORDS: Oxcarbazepine, Poly ethylene oxide, Ethylcellulose N50, contolled release tablets.

 

 


INTRODUCTION:

Oral drug delivery is the most widely utilized route of administration among all the routes that have been explored for systemic delivery of drugs via pharmaceutical products of different dosage form. Oral route is considered most natural, convenient and safe due to its ease of administration, patient acceptance, and cost effective manufacturing process. Pharmaceutical products designed for oral delivery are mainly immediate release type or conventional drug delivery systems, which are designed for immediate release of drug for rapid absorption.1

 

 

 

 

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 effects.2,3

 

Historically, oral drug administration has been the predominant route for drug delivery. It is known to be the most popular route of drug administration due to the fact the gastrointestinal physiology offers more flexibility in dosage form design than most other routes A major challenge for the pharmaceutical industry in drug development is to produce safe and efficient drugs, therefore properties of drugs and the way in which they are delivered must be optimised.4,5

 

A controlled release drug delivery system delivers the drug locally or systemically at a predetermined rate for a specified period of time The goal of such systems is to provide desirable delivery profiles that can achieve therapeutic plasma levels. Drug release is dependent on polymer properties, thus the application of these properties can produce well characterised and reproducible dosage forms.6,7

 

The basic rationale of a controlled release drug delivery system is to optimize the biopharmaceutics, pharmacokinetics, and pharmacodynamics properties of a drug in such a way that its utility is maximized through reduction in side effects and cure or control of disease condition in the shortest possible time by using smallest quantity of drug, administered by most suitable route. The immediate release drug delivery system lacks some features like dose maintenance, controlled release rate and site targeting. An ideal drug delivery system should deliver the drug at a rate dictated by the need of body over a specified period of treatment.8,9,10

 

MATERIALS :

Oxcarbazepinewas procured from Glenmark Pharmaceuticals, Provided bySURA LABS; Poly EthyleneOxide, HPMC K15M, EthylcelluloseN50, Talc, Mg Stearate, Mannitol were procured from Merck ChemicalsSpecialities Pvt Ltd, Mumbai, India, Provided by SURA Labs, Dilsukhnagar.


 

METHODOLOGY:

Table 1: Formulation composition for tablets

Ingredients

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12

Oxcarbazepine

50

50

50

50

50

50

50

50

50

50

50

50

Poly ethylene

Oxide

10

20

30

40

-

-

-

-

-

-

-

-

HPMC K15M

-

-

-

-

10

20

30

40

-

-

-

-

Ethylcellulose

N50

-

-

-

-

-

-

-

-

10

20

30

40

Talc

3

3

3

3

3

3

3

3

3

3

3

3

Mg stearate

3

3

3

3

3

3

3

3

3

3

3

3

Mannitol

184

174

164

154

184

174

164

154

184

174

164

154

Total weight

250

250

250

250

250

250

250

250

250

250

250

250

All the quantities were in mg

 


Evaluation:

As per standard procedures from IP, USP

 

RESULTS AND DISCUSSION:

Standard Calibration curve of Oxcarbazepine:

 

Table 2: Concentration and absorbance obtained for calibration curve of Oxcarbazepine in0.1 N hydrochloric acid buffer (pH 1.2)

S. No.

Concentration (µg/ml)

Absorbance* (at 254 nm )

1

0

0

2

10

0.195

3

20

0.386

4

30

0.571

5

40

0.743

6

50

0.948

 

It was found that the estimation of Oxcarbazepine by UV spectrophotometric method at λmax254 nm in 0.1N Hydrochloric acid had good reproducibility and this method was used in the study. The correlation coefficient for the standard curve was found to be closer to 1, at the concentration range, 2-10μg/ml.

 

Fig 1: Standard graph of Oxcarbazepine in 0.1 N HCl

 

Table 3: Concentration and absorbance obtained for calibration curve of Oxcarbazepine in pH 6.8 Phosphate buffer.

S. No.

Concentration (µg/ml)

Absorbance* (at 254 nm)

1

0

0

2

2

0.198

3

4

0.392

4

6

0.568

5

8

0.723

6

10

0.896

 

 

It was found that the estimation of Oxcarbazepine by UV spectrophotometric method at λmax254 nm in pH 6.8 Phosphate buffer. It had good reproducibility and this method was used in the study. The correlation coefficient for the standard curve was found to be closer to 1, at the concentration range, 2-10μg/ml.

 

 

Fig 2: Standard graph of Oxcarbazepine in pH 6.8 Phosphate buffer

 

FTIR

 

Fig 3: FT-TR Spectrum of Oxcarbazepine pure drug

 

 

Fig 4: FT-IR Spectrum of Optimised Formulation

There is no incompatibility of pure drug and excipients. There is no disappearance of peaks of pure drug and in optimized formulation.

 

Evaluation Parameters for sustained release tablets of Oxcarbazepine:

Table 4: Pre-compression parameters

Formulations

Bulk Density(gm/cm2)

Tap Density

(gm/cm2)

Carr’s Index

 (%)

Hausner ratio

Angle Of Repose(Ɵ)

F1

0.47

0.55

14.54

1.17

28.23

F2

0.45

0.55

18.18

1.22

27.91

F3

0.46

0.55

16.36

1.19

26.71

F4

0.46

0.55

16.36

1.19

26.71

F5

0.47

0.55

14.54

1.17

28.23

F6

0.50

0.58

13.79

1.16

29.34

F7

0.41

0.50

18

1.21

26.78

F8

0.50

0.58

13.79

1.16

29.34

F9

0.41

0.50

18

1.21

26.78

F10

0.44

0.54

18.05

1.22

27.02

F11

0.42

0.52

19.23

1.23

30.11

F12

0.46

0.57

19.29

1.23

24.22

 

Post compression Parameters:

Table 5: post compression parameters

FD

Average Weight

(mg)

Hardness (kg/cm2)

Thickness

(mm)

Friability

(%)

Assay (%)

F1

248

4.4

5.6

0.42

98.25

F2

246

4.2

5.7

0.40

97.53

F3

249

4.1

5.8

0.50

99.15

F4

248

 4.3

5.8

0.49

98.35

F5

246

4.2

5.8

0.42

99.17

F6

249

4.5

5.7

0.31

97.56

F7

247

4.3

5.8

0.35

99.17

F8

245

4.2

5.8

0.31

98.26

F9

249

4.3

5.8

0.35

99.24

F10

248

4.4

5.9

0.36

99.68

F11

249

4.6

5.6

0.37

99.75

F12

250

4.5

5.5

0.39

99.45

 

 

Fig 5: Dissolution profile of formulations prepared with Poly ethyleneoxide polymer

 

 

 


 

Table 6: 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

8.33

3.33

4.56

6.54

14.55

13.32

12.14

12.78

15.14

11.05

13.52

12.02

1

17.46

11.17

23.71

16.12

17.47

16.45

16.12

17.55

19.66

16.55

15.41

17.50

2

23.21

19.52

38.72

20.25

26.62

25.62

19.32

20.02

26.28

22.1

20.35

22.30

3

49.55

23.88

42.28

25.54

31.47

32.85

26.16

28.65

33.76

29.54

27.08

30.28

4

55.45

34.59

49.83

32.14

39.12

40.71

32.47

34.21

39.84

34.82

36.63

36.15

5

60.12

46.65

56.79

38.10

42.85

46.15

45.62

48.88

46.48

56.47

42.58

40.89

6

67.5

51.56

61.10

46.65

48.41

52.78

57.45

52.98

53.96

63.45

54.1

46.22

7

72.01

58.12

64.09

51.14

56.65

63.32

60.63

62.87

60.67

69.74

66.63

52.65

8

78.10

62.1

69.89

57.13

61.12

69.41

72.74

68.2

69.82

78.52

75.45

60.85

9

82.29

67.13

70.99

63.26

69.56

73.23

78.85

75.23

68.17

86.64

82.87

69.74

10

86.10

73.21

74.02

70.34

72.14

76.14

83.70

86.51

75.82

91.34

86.34

73.31

11

90.11

78.11

78.09

75.09

77.81

79.49

86.09

90.65

88.79

95.45

89.74

79.63

12

91.05

82.56

80.1

78.85

80.32

83.75

93.45

95.26

92.73

98.84

94.14

82.32

 


 

Fig 6: Dissolution profile of formulations prepared with Hpmc K15m polymer

 

Fig 7: Dissolution profile of formulations prepared with Ethyl celluloseN50as polymer


 

 

 

 

 

Table7: 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

11.05

0.5

0.707

1.158

-0.301

1.932

28.800

0.0694

-0.842

85.6

4.642

4.407

0.234

16.55

1

1.000

1.272

0.000

1.910

18.700

0.0535

-0.728

81.3

4.642

4.332

0.310

22.1

2

1.414

1.391

0.301

1.877

12.300

0.0407

-0.609

75.4

4.642

4.225

0.417

29.54

3

1.732

1.511

0.477

1.830

10.800

0.0309

-0.489

67.6

4.642

4.074

0.568

34.82

4

2.000

1.606

0.602

1.775

10.100

0.0248

-0.394

59.6

4.642

3.906

0.735

56.47

5

2.236

1.685

0.699

1.713

9.680

0.0207

-0.315

51.6

4.642

3.723

0.919

63.45

6

2.449

1.728

0.778

1.668

8.900

0.0187

-0.272

46.6

4.642

3.599

1.043

69.74

7

2.646

1.760

0.845

1.628

8.214

0.0174

-0.240

42.5

4.642

3.490

1.152

78.52

8

2.828

1.822

0.903

1.528

8.288

0.0151

-0.178

33.7

4.642

3.230

1.412

86.64

9

3.000

1.861

0.954

1.437

8.071

0.0138

-0.139

27.36

4.642

3.013

1.628

91.34

10

3.162

1.905

1.000

1.293

8.036

0.0124

-0.095

19.64

4.642

2.698

1.944

95.45

11

3.317

1.939

1.041

1.116

7.903

0.0115

-0.061

13.07

4.642

2.356

2.286

98.84

12

3.464

1.979

1.000

0.666

7.948

0.0105

-0.021

4.63

4.642

1.667

2.975

 


 

Fig 8: Zero order release kinetics

 

 

Fig 9 (A) : Higuchi release kinetics graph

 

 

Fig 9 (B) : Kars mayerpeppas graph

 

CONCLUSION:

In the present work, an attempt has been made to develop controlled release tablets of Oxcarbazepine by selecting Poly ethyleneoxide, HPMC K15M, EthylcelluloseN50as retarding 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. Among all the formulations F10 formulation showed maximum % drug release i.e., 98.84 % in 12 hours hence it is considered as optimized formulation F10 which contains Ethylcellulose N50 (20mg) . It was evident that the formulation F10 was followed Zero order release mechanism.

 

 

Fig 10: First order release kinetics graph

 

ACKNOWLWDGEMENT:

The authors are thankful to SURA Labs Dilshukhnagar, Hyderabad, T.S., India for providingthe necessary facilities for the research work.

 

REFERENCES:

1.     Sathish Ummadi, B. Shravani, N. G. Raghavendra Rao, M. Srikanth Reddy, B. Sanjeev Nayak.

1.Overview on Controlled Release Dosage Form. International Journal of Pharma SciencesVol. 3, No. 4 (2013): 258-269.

2.     Brahmankar D.M. and Jaiswal S.B. (1995): “Biopharmaceutics and Pharmacokinetics” a Treatise. Vallabh Prakashan, First Edition; 336-337.

3.     Lachman Leon, Lieberman Herbert A., Kanig Joseph L. (1996) “The Theory and Practice of Industrial Pharmacy” Second edition, Varghese Publishing House; Bombay, 171-196.

4.     Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics: Pharmacokinetics. 2nd ed. Vallabh Prakashan, Delhi: 2009; 399-401.

5.     John C, Morten C, The Science of Dosage Form Design, Aulton: Modified release peroral dosage forms. 2nd ed. Churchill Livingstone. 2002; 290-300.

6.     Ali Nokhodchi, ShaistaRaja, Pryia Patel, and Kofi Asare-Addo.The Role of Oral Controlled Release Matrix Tablets in Drug Delivery Systems.Bioimpacts. 2012; 2(4): 175–187.

7.     John C, Morten C, The Science of Dosage Form Design, Aulton: Modified release peroral dosage forms. 2nd ed. Churchill Livingstone. 2002; 290-300.

8.     Sathish Ummadi, B. Shravani, N. G. Raghavendra Rao, M. Srikanth Reddy, B. SanjeevNayak.Overview on Controlled Release Dosage Form. International Journal of Pharma Sciences. Vol. 3, No. 4 (2013): 258-269.

9.     Vyas S,P, Khar RK. Controlled Drug delivery: Concepts and Advances. Concepts and Advances.1st ed. Vallabh Prakashan, 2002, p,156-189.

10.  Shargel L, Yu ABC. Modified release drug products. In: Applied Biopharmaceutics and Pharmacokinetics. 4th ed. McGraw Hill.1999; 169-171.

 

 

 

Received on 26.04.2019          Accepted on 06.05.2019         

© Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech.  2019; 9(2):107-111.

DOI: 10.5958/2231-5713.2019.00018.7