Umesh Prajapati Final

8/6/2019 Umesh Prajapati Final

1/29

, &O R M U L A T I O N D E V E L O P M E N T E V A L U T I O N O F&O R M U L A T I O N D E V E L O P M E N T E V A L U T I O N O F X T E N D E D R E L E A S E T A B L E T O F A N T I E P I L E P T I C X T E N D E D R E L E A S E T A B L E T O F A N T I E P I L E P T I C

R U GR U G

Guided By.M r sha ilesh S h arm a

. ( )M Pharm G u idePresented by

.M r U m eshPra ja p a ti

.M Pharam( )P Ceutics

Department of Pharmaceutics, NIMS Institute of Pharmacy, JAIPUR

o n e o n ea tt .Y D U S C A D IL A H E LT H C A R E LT D

Industrial Guide :( -M s A rtiPo td a r C o

)g u id e


2/29

INDEX

1. Objective

2. Drug and Excipients

3. Formulation, Development &

Evaluation

4. Stability study5. Conclusion

1.


3/29

1.O BJ EC T I V E


4/29

OBJECTIVE To formulate stable, effective and optimum Extended

release dosage form

To study the effect of different excipients in theformulation.

To evaluate the prepared Extended release dosage forms.

To perform the stability studies.

In this work effect of polymer will be observed ondrug release .


5/29

2. DRUG AND EXCIPIENT


6/29

DRUG AND EXCIPIENTSAPI1. Category Anti-epileptic

2. Mol. mass 250.294 g/mol

3. Boiling point 697.3 C

4. Melt. Point 142 - 146 C

5. Solubility BCS class-I, Highly soluble

6. Description A white to Off-white to powder

7. Metabolism Hepatic

8. Half life 13 hours

9. Time to peak plasma 4 hrs

10. Route Oral, IV

11. BCS class I

12. Excretion 40% as conjugated metabolite inurine


7/29

ExcipientsIngredients Function

AED API

Lactose monohydrate Diluent

Hydroxypropaylmethaylcellulose(HPMC K100 M) Matrix-forming polymer

Hydroxypropaylmethaylcellulose (HPMC K4M) Matrix-forming polymer

Hydroxypropaylmethaylcellulose (HPMC K15M) Matrix-forming polymer

Isopropaylalcohol (IPA) Binder solution

Microcrystalline cellulose(MCC) Diluent

Colloidal silicon dioxide Glidant (0.25-3%)

Talc Glidant

Magnesium stearate Lubricant (0.25-4%)


8/29

3 .PREF ORM U LA T I O N

3 .PREFO RM U LA T I O N

S T U D Y S T U D Y


9/29

Drug- Excipient Compatibility StudySr. No. Ingredients

Ratio of Drymix Drug:Excipient

Initial 1 week 2week 3 week 4 week

1 API -- Whitecrystalline

powder

No change No change No change No change

2 LACTOSEMONOHYDRETE

1:1 Whitecrystalline

powder


3 HPMC K4M 1:1 Whitecrystalline

powder


4HPMCK100M


powder


5 HPMCK15M


powder



10/29

6Microcrystallinecellulose(MCC) 1:1

White crystalline powder


7 Colloidalsilicondioxide

1:1 White crystalline powder


8 TALC 1:1 White crystalline powder


9 Magnesiumstearate

1:1 White crystalline powder



11/29

PHYSICAL PROPERTY OF API

Result of preformulation study of APIDrug Angle of

repose(0)

Loose bulk density(g/ml)

Tapped bulk density(g/ml)

Carrsindex(%)

Hausner'sratio

API 22.22 0.35 0.49 39.45 1.40


12/29

Description: A white to off-white powder

Related substances: Unknown Impurities: :NOT MORE THAN 0.1%Total Impurities: NOT MORE THAN 0.5%

Assay by HPLC 99.87%

Loss of drying 0.67% (Not more than 1.0%)

Melting point 142~146c

Half life: 13 hour


13/29

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 .


14/29

Theoretical Release profile InVitro Release study of Theoretical and Hypothetical Release profile

Dissolution 900ml, USP - II (Paddle) Apparatus, 50 RPM

Time (hrs.) Theoretical % Drug Release Hypothetical % Drug Release

0.1N HCL

1 23.9 15-25%

2 36 30-35%

PH6.8 Phosphate buffer

4 53.5 50-55%

8 89.6 85-90%

12 97.6 NLT 90%


15/29

4.4. METHODOLOGYMETHODOLOGY


16/29

Sr.no Ingredient F1 F2 F3 F4 F5 F6 F7

1 API 300 300 300 300 300 300 300

2 Lactose

mono hydrete

177 177 169.5 162 162 162 162

3 HPMC K4M - - - - 10 20 30

4 HPMCK15M

40 - - - - - -

5 HPMCK100M

- 40 50 60 50 40 30

6 IPA Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S.

7 MCC 59 59 56.5 54 54 54 54

8 Colloidalsiliconedioxide

6 6 6 6 6 6 6

9 TALC 12 12 12 12 12 12 12

10 Mg.sterate 6 6 6 6 6 6 6

TOTAL 600 600 600 600 600 600 600

Formulation compositions of AED


17/29

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)

Tappeddensity(g/ml)

Carrs index(%) Hausners ratio

F/1 24.69 0.462 0.524 11.83 1.13

F/2 23.31 0.438 0.517 15.28 1.18

F/3 24.31 0.431 0.504 14.48 1.17

F/4 25.14 0.459 0.534 14.04 1.16

F/5 23.31 0.459 0.534 14.48 1.18

F/6 24.31 0.456 0.529 15.28 1.18

F/7 24.31 0.456 0.529 14.48 1.17


18/29

Evaluation Of Tablet Result of evaluation of tablets of trial batches F/1 to F/7

Trial batchesHardness (kP)

Thickness(mm) Friability (%) Avg. Wt.

(mg)

Assay (%)

F1 16-17 5.41-5.42 Nil 600 98.80

F2 16-17 5.41-5.42 Nil 600 97.5

F3 16-17 5.41-5.42 Nil 600 97.6

F4 16-17 5.41-5.42 Nil 600 98.7

F5 16-17 5.41-5.42 Nil 600 97.8

F6 16-17 5.41-5.42 Nil 600 98.4

F7 16-17 5.41-5.42 Nil 600 94.3


19/29

5 . DRU G RELEA S E PRO F I LE


20/29

Drug release profile of trail F/1 to F/7

Time (hrs.) F/1 F/2 F/3 F/4F/5 F/6 F/7

0.1N HCL

1 62.2 60.8 55.4 49.436.6 25.9 23.9

2 85.8 64.2 63.8 45.844.2 39.1 35.9

PH6.8phosphete buffer

4 98.7 87.6 79.8 69.955.6 58.9 53.4

8 97.2 97 98.4 9969.8 92.1 89.7

12 95.1 96.9 96.5 98.381.9 89.4 97.4


21/29

Time

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

Dissolution Parameter : :Dissolution Media . / .0 1N HCL PH6 8Phosphet Buffer :Temperature 37+ 2 C :Volume of Medium 900ml :Sample Drawn 10 ml :Apparatus Basket . . .:R P M 100 :Dilution 5ml in 100ml


22/29

6.STABILITY STUDY


23/29

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

Base foil: PVC/PVDC blister pack.

Lidding Material : 0.025 mm aluminum foil

Justification: PVC/PVDC Blister pack provides complete protection

against

light, water vapour, gases etc.

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

l f b l b h f h


24/29

Evaluation parameters of stability batch after 1 months

FormulationCode

Parameters Storage time

0 month 1 month

Drug content,%

101.34

100.24

Physicalappearance

No discolor- ation No discolor-ation

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

Time(min) Initial After 1months

1 23.9 23.32 35.9 32.2

4 53.4 50.0

8 89.7 85.01

12 97.4 95


25/29


26/29

7.CONCLUSION


27/29

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 theformulation 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 requirementof extended release tablet and study encourages further

clinical trials and long term stability study on this

formulation


28/29

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. 3 rd Ed.; Marcel Dekker Inc; New York; 575-609.

Lachman L, Lieberman HA, Kanig JL., 1987, The theory and practice of industrial pharmacy, 3 rd Ed.; Varghese Publishing House Bombay, 293-345,430.

Hui HW, Robinson JR, Lee VHL. Design and fabrication of oral controlledrelease drug delivery systems. In: Robinson JR, Lee V, editors. Controlleddrug delivery fundamentals and applications. 2 nd Ed.; Marcel Dekker: NewYork: Inc; p. 373-4..

Ben-Menachem, E. Lacosamide: an investigational drug foradjunctive treatment of partial-onset seizures. Drugs of Today2007; 43 Available at: www.prous.com/journals

ICH GUIDELINES Q1A (R2), Guidance for industry, stabilitytesting of new drug substance and products (Available on:http:// http://www.ich.org).

The Indian Pharmacopoeia; Ministry of Health and FamilyWelfare Government of India Controller of Publications New


29/29

Documents

Umesh Prajapati Final