FORMULATION , DEVELOPMENT & EVALUTION OF EXTENDED RELEASE TABLET OF ANTIEPILEPTIC

DRUG

Guided By Mr.shailesh Sharma M.Pharm (Guide)

Presented by Mr . Umesh Prajapati M . Pharam ( P Ceutics )

Department of Pharmaceutics, NIMS Institute of Pharmacy, JAIPUR

INDEX
1. Objective 2. Drug and Excipients 3. Formulation, Evaluation 4. Stability study 5. Conclusion

Development

&

1.

1.O

IV E CT JE B

OBJECTIVE
To formulate stable, effective and optimum Extended release dosage form To study the effect of different excipients in the formulation. To evaluate the prepared Extended release dosage forms. To perform the stability studies. In this work effect of polymer will be observed on drug release.

2. DRUG AND EXCIPIENT

DRUG AND EXCIPIENTS

API
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Category Mol. mass Boiling point Melt. Point Solubility Description Metabolism Half life Time to peak plasma Route BCS class Excretion Anti-epileptic 250.294 g/mol 697.3 C 142 - 146 C BCS class-I, Highly soluble A white to Off-white to powder Hepatic 13 hours 4 hrs Oral, IV I 40% as conjugated metabolite in urine

Excipients
Ingredients AED Lactose monohydrate Hydroxypropaylmethaylcellulose(HPMC K100 M) Hydroxypropaylmethaylcellulose (HPMC K4M) Hydroxypropaylmethaylcellulose (HPMC K15M) Isopropaylalcohol (IPA) Microcrystalline cellulose(MCC) Colloidal silicon dioxide Talc Magnesium stearate Function API Diluent Matrix-forming polymer Matrix-forming polymer Matrix-forming polymer Binder solution Diluent Glidant (0.25-3%) Glidant Lubricant (0.25-4%)

MULATION 3.PREFOR STUDY

Drug- Excipient Compatibility Study

Sr. No. Ingredients Ratio of Dry mix Drug: Excipient -Initial 1 week 2week 3 week 4 week

API

White crystalline powder White crystalline powder

No change

No change

No change

No change

LACTOSE 1:1 MONOHYDRETE

No change

No change

No change

No change

HPMC K4M 1:1

White crystalline powder White crystalline powder

No change

No change

No change

No change

HPMC K100M

1:1

No change

No change

No change

No change

HPMC K15M

1:1

White crystalline powder

No change

No change

No change

No change

White crystalline No change powder 6

No change

No change

No change

Microcrystallin e cellulose(MCC) 1:1

Colloidal silicon dioxide

1:1

White crystalline No change powder

No change

No change

No change

TALC

1:1

White crystalline No change powder

No change

No change

No change

Magnesium stearate

1:1

White crystalline No change powder

No change

No change

No change

PHYSICAL PROPERTY OF API

Result of preformulation study of API Angle of Loose bulk Tapped bulk Carrs repose density density index (g/ml) (g/ml) (%) (0 )

Drug

Hausner's ratio

API

22.22

0.35

0.49

39.45

1.40

Description: Related substances:

A white to off-white powder Unknown Impurities: :NOT MORE THAN 0.1% Total Impurities: NOT MORE THAN 0.5% 99.87% 0.67% (Not more than 1.0%) 142~146c 13 hour

Assay by HPLC Loss of drying Melting point Half life:

Particle size analysis

( By Malvern master seizer, dry method)

For many active substances, particle size has an impact on powder flow; content uniformity and drug dissolution. In order to assure consistent product quality, the particle size of the API has been characterized. From the results obtained, the limits will be derived which will be routinely applied by the API manufacturer during analysis of drug. Particle size of drug was determined by Malvern particle size analyzer.

D (0.10) = 2.39 , D (0.50) = 7.37 , D (0.90) = 19.46 .

Theoretical Release profile

InVitro Release study of Theoretical and Hypothetical Release profile Dissolution Time (hrs.) 0.1N HCL 1 2 23.9 36 PH6.8 Phosphate buffer 4 8 12 53.5 89.6 97.6 50-55% 85-90% NLT 90% 15-25% 30-35% 900ml, USP - II (Paddle) Apparatus, 50 RPM Theoretical % Drug Release Hypothetical % Drug Release

4.METHODOLOGY

Sr.no 1 2

Ingredient API

F1 300

Formulation compositions of AED

F2 F3 F4 300 177 300 169.5 300 162

F5 300 162

F6 300 162

F7 300 162

Lactose 177 mono hydrete HPMC K4M HPMC K15M HPMC K100M IPA MCC Colloidal silicone dioxide TALC Mg.sterate 40 Q.S. 59 6

3 4 5 6 7 8

40 Q.S. 59 6

50 Q.S. 56.5 6

60 Q.S. 54 6

10 50 Q.S. 54 6

20 40 Q.S. 54 6

30 30 Q.S. 54 6

9 10 TOTAL

12 6 600

12 6 600

12 6 600

12 6 600

12 6 600

12 6 600

12 6 600

Evaluation of blend
Result of evaluation of powder blend of trial batches F/1 to F/7 Trails Angle of repose () Bulk density(g/ml) Tapped density(g/ml) Carrs index(%) Hausners ratio

F/1 F/2 F/3 F/4 F/5 F/6 F/7

24.69 23.31 24.31 25.14 23.31 24.31 24.31

0.462 0.438 0.431 0.459 0.459 0.456 0.456

0.524 0.517 0.504 0.534 0.534 0.529 0.529

11.83 15.28 14.48 14.04 14.48 15.28 14.48

1.13 1.18 1.17 1.16 1.18 1.18 1.17

Evaluation Of Tablet
Result of evaluation of tablets of trial batches F/1 to F/7 Trial batches Hardness (kP) Thickness (mm) Friability (%) Avg. Wt. (mg) Assay (%)

F1 F2

16-17 16-17

5.41-5.42 5.41-5.42

Nil Nil

600 600

98.80 97.5

F3 F4 F5 F6 F7

16-17 16-17 16-17 16-17 16-17

5.41-5.42 5.41-5.42 5.41-5.42 5.41-5.42 5.41-5.42

Nil Nil Nil Nil Nil

600 600 600 600 600

97.6 98.7 97.8 98.4 94.3

ASE PROFILE 5.DRUG RELE

Drug release profile of trail F/1 to F/7 Time (hrs.) F/1 F/2 F/3 F/4 F/5 F/6 F/7

0.1N HCL 1 62.2 60.8 55.4 49.4 36.6 2 85.8 64.2 63.8 45.8 44.2 39.1 35.9 25.9 23.9

PH6.8phosphete buffer 4 98.7 87.6 79.8 69.9 55.6 8 97.2 97 98.4 99 69.8 12 95.1 96.9 96.5 98.3 81.9 89.4 97.4 92.1 89.7 58.9 53.4

Dissolution Parameter :

Dissolution Media: Temperature: Volume of Medium: Sample Drawn: Apparatus: R.P.M.: Dilution:

100

0.1N HCL/ PH6.8Phosphet Buffer 37+ 2C 900ml 10 ml Basket 5ml in 100ml

Time
Dissolution data of drug release F1 to F3 Dissolution data of drug release F4 to F7

6.STABILITY STUDY

STABILITY STUDY
Tablets was packed in a blister formed by the following primary packaging components.

Base foil: Lidding Material: Justification:

PVC/PVDC blister pack. 0.025 mm aluminum foil PVC/PVDC Blister pack provides complete protection light, water vapour, gases etc.

against

The ICH Guidelines have established that long term stability testing should be done at 25C2C / 60%5% RH; stress testing should be done at 40C2C / 75%5% RH for 6 months

Evaluation parameters of stability batch after 1 months Parameters Storage time 0 month 1 month Formulation Code Drug content, 101.34 100.24 %

Physical appearance

No discolor- ation

No discolor-ation

Comparison of dissolution of optimized tablet (F07) of initial and after 1 months Time(min) 1 2 4 8 12 Initial 23.9 35.9 53.4 89.7 97.4 32.2 50.0 85.01 95 After 1months 23.3

Comparison of dissolution of optimized tablet (F07) of initial and after 1 months

7.CONCLUSION

CONCLUSION
The study was undertaken with the aim to Formulation and evaluation of Antiepileptic extended release tablet using HPMC grade of polymer as retarding agent. From the above results and discussion, it is concluded that the formulation of extended release tablet of Antiepileptic drug containing HPMC K100+HPMC K4M, which are taken as ideal or optimized formulation of extended release tablet for 12 hours release as it fulfils all the requirement of extended release tablet and study encourages further clinical trials and long term stability study on this formulation

References
Chien YW, 1992,. Novel drug delivery systems, 2nd Edition; Marcel Dekker Inc: New York, 139-40. Jantzen GM, Robinson JR, 1996, Sustained- and controlled-release drug delivery systems. In: Banker GS, Rhodes CT, editors. Modern pharmaceutics. 3rd Ed.; Marcel Dekker Inc; New York; 575-609. Lachman L, Lieberman HA, Kanig JL., 1987, The theory and practice of industrial pharmacy, 3rd Ed.; Varghese Publishing House Bombay, 293345,430. Hui HW, Robinson JR, Lee VHL. Design and fabrication of oral controlled release drug delivery systems. In: Robinson JR, Lee V, editors. Controlled drug delivery fundamentals and applications. 2nd Ed.; Marcel Dekker: New York: Inc; p. 373-4.. Ben-Menachem, E. Lacosamide: an investigational drug for adjunctive treatment of partial-onset seizures. Drugs of Today 2007; 43 Available at: www.prous.com/journals ICH GUIDELINES Q1A (R2), Guidance for industry, stability testing of new drug substance and products (Available on: http:// http://www.ich.org). The Indian Pharmacopoeia; Ministry of Health and Family Welfare, Government of India, Controller of Publications, New