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, &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
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INDEX
1. Objective
2. Drug and Excipients
3. Formulation, Development &
Evaluation
4. Stability study5. Conclusion
1.
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1.O BJ EC T I V E
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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 .
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2. DRUG AND EXCIPIENT
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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
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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%)
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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
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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
No change No change No change No change
3 HPMC K4M 1:1 Whitecrystalline
powder
No change No change No change No change
4HPMCK100M
1:1 Whitecrystalline
powder
No change No change No change No change
5 HPMCK15M
1:1 Whitecrystalline
powder
No change No change No change No change
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6Microcrystallinecellulose(MCC) 1:1
White crystalline powder
No change No change No change No change
7 Colloidalsilicondioxide
1:1 White crystalline powder
No change No change No change No change
8 TALC 1:1 White crystalline powder
No change No change No change No change
9 Magnesiumstearate
1:1 White crystalline powder
No change No change No change No change
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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
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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
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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 .
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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%
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4.4. METHODOLOGYMETHODOLOGY
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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
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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
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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
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5 . DRU G RELEA S E PRO F I LE
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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
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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
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6.STABILITY STUDY
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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
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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
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7.CONCLUSION
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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
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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
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