1. Presented By Guided By
Mr. Gajanan S. Ingole Mr. K.B. Charhate
ANURADHA COLLEGE OF PHARMACY,
CHIKHLI.

2. 1. Introduction
2. Literature review
3. Drug and excipients profile
4. Aim and objective
5. Rational and plan of work
6. Materials and equpiments
7. Experimental work
8. Results
9. Discussion
10. Conclusion
11. References
2

3. Oral delivery of drugs is the most convenient route of Drug delivery systems due
to
 Ease of administration
 Patient compliance
 Flexibility in formulation
Tablets
ingested
orally
Tablets used
in oral
cavity
Tablets
administere
d by other
route
Tablets
administere
d by other
route
Tablets used
to prepare
solution
Matrix Tablets
Type of controlled drug delivery systems, which release the drug in continuous
manner.
a matrix is defined as a well-mixed composite of one or more drugs with gelling
agent i.e. hydrophilic.
release the drug by both controlled and diffusion controlled mechanisms.
3

4. Easy to manufacture,effective
and low cost .
avoids the high blood
concentration.
maintain therapeutic
concentrations over
prolonged periods.
Reduce the toxicity.
Minimize the local and
systemic side effects.
Increase the stability.
4
The remaining matrix must be
removed after the drug has
been released.
The release rates are affected
by various factors such as, food
and the rate transit through the
gut.
Release rate continuously
diminishes due to an increase in
diffusional resistance

5. A)On the Basis of Retardant Material Used
• Hydrophobic Matrices
• Lipid Matrices
• Hydrophilic Matrices
• Biodegradable Matrices
• Mineral Matrices
B)On the Basis of Porosity of Matrix
• Macroporous Systems
• Microporous System
• Non-porous System
5

6. POLYMERS EXAMPLE
i) Hydrogels Polyhydroxyethyl methylacrylate.
ii) Soluble polymers Polyethylene glycol (PEG)
iii)Biodegradable polymers Polylaceticacid (PLA)
iv)Non biodegradable polymers Polyethylene vinyl acetate.(PVA)
v)Mucoadhesivepolymers Sodium carboxymethyl cellulose.
6

7.  Specific polymers have been designed to release drugs into
specific regions of the gastrointestinal tract.
A)pH dependent polymer:
EudragitE,EudragitL,EudragitS,Hydroxyproylmethylcellulose
phthalate.
B)pH independent polymer:
Hydroxy propyl methyl cellulose, Kollidon.
7

8.  Kumar et al; in their review “Oral Extended Release Drug Delivery System”
providing the recent literature regarding development and design of extended
release tablets.
 Patel et al; in their Overview “Extended Release Matrix Technology” This
article contains the basic information regarding extended-release formulation
and also the different types of the same.
 Patel et al; in their review “Matrix Type Drug Delivery System: A Review”
Focused on to formulate tablets in order to avoid the first pass metabolism
and increase the bioavailability. Hence in this work an attempt was made to
formulate sustain release. system for in order to achieve even plasma
concentration profile up to 24 hrs. it can be easily concluded that sustained-
release formulation are helpful in increasing the efficiency of the dose as well
as they are also improving the patient’s compatibility.
 Mulani H et al, in their research work pH independent sustained release
matrix tablet was formulated. It was found that Kollidon® SR is suitable for
pH-independent extended release matrix tablets.
 Pao-Chu Wu et al; their study was to develop and optimize the propranolol
once-daily extended release formulations containing HPMC,Microcrystalline
cellulose (MCC) and lactose.
8

9. Drug Profile
Name:
NSL
Assay:101.
4 %w/w
(By HPLC,
on dried
base).
Solubility:
soluble in
ethanol and
insoluble in
water.
Half-life:
Plasma
half-life is
7-12 hrs
Description:
yellow
crystalline
powder
Category:
calcium
channel
blockers
Loss on
drying:
0.15% (By
Karl
Fisher)
9

10. Clinical
Pharmacology
Mechanism
of Action
Distribution
Metabolism
Elimination
Uses
Contraindic
ation
10

11. Excipients Profile
Lactose
Monohydrate
Sodium Lauryl
Sulfate
Cellulose
Microcrystalline
Magnesium
Stearate
Colloidal Silicon
Dioxide
Instacoat
Universal Brown
11

12. Polymer Profile
Hydroxypropylmethylcellulose
Polymethacrylates
12

13. Aim:
 The aim of present study is to develop & characterized matrix
tablet of antihypertensive drug using pH dependent and
independent polymer.
Objectives:
 To deliver the dosage form at the site of absorption their by
enhancing the bioavailability.
 To delay and control the release of drug through the formulation.
 To match the invitro dissolution profile of marketed reference
product.
 To formulate Site specific drug delivery.
 To formulate Stable formulation.
 To formulate Cost effective dosages form with respect to marketed
reference product.
13

14.  RATIONAL
 Antihypertensive therapy has a well established place to prevent the
complications of high blood pressure.
 Amongst the existing agents NSL is effective ones.
 formulation of matrix tablet provides an increase in the bioavailability of
calcium channel blocker.
 Manufacturing of Antihypertensive drug is easy.
 reduces the frequency of administration
 improves patient compliance, better selectivity and longer duration of
action.
14

15. PLAN OF
WORK
Literature
survey.
Selection of
material
Preformulation
studies.
Drug
excipients
compatibility
studies
Preparation
of various
formulations
Evaluation
of tablet
Stability
Studies
Result and
Discussion
Conclusion
15

16. Sr.
No.
Parameters Observations
1 Dosage form Solid Oral
2 Brand name of the product Sular
3
Generic name of the
product
NSL tablet
4 Manufactured by Skye pharma production SAS
5 Label claim Each tablet contain 34 mg of NSL
6 Description
Orange oval tablet with SC1503 marking one side
&plain other side
7
Excipients
Hypromellose,Lactose, Hypromellose phthalate,
Glyceryl behenate, Silicon dioxide,SLS,Povidone,
Magnesium sterate, Methacrylic acid copolymer.
8 Thickness(nm) 6.76-6.88
9 Hardness(N) 160
10 Container HDPE
11 Storage 20-250C Protect from light & moisture16

17. Preformulation
Study
Formulation of
matrix tablet
Optimization Study
Stability
Studies
17

18. A)Preformulation
Study
a)Characterstics of the
Bulk Drug and Powder
Blend Properties
1)Bulk density
2)Tapped density
3)Compressibility
index
4)Hausner’s ratio
5) Loss on drying
(LOD)
b)Drug Excipient
Compatibility Study
18

19. Sr. No
Ingredients
Trial Batches in mg
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
Intragranular
1 NSL 34 34 34 34 34 34 34 34 34 34
2
Hypromellose (Methocel prem
K100LV) 50 50 - - - - - - - -
3
Lactose monohydrate (pharmatose
200M) 30 30 30 30 46.6 38.3 38.3 38.3 76.6
4
Methacrylic Acid Copolymer
Eudragit L10055 - - 50 36 56 46 46 46 46 46
5
Microcrystalline cellulose (Avicel
PH101) 140.4 136.8 136.8 136.8 231.8 184.2 214.9 168.9 253.2 176.6
6
Sodium lauryl
sulphate(Texaponk12pPH) - 3.6 3.6 3.6 5.6 4.6 4.6 4.6 4.6 4.6
Binder
7 IPA q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s
8 Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s
Extragranular
9 Hypromellose(Methocel K100CR) 100 100 100 114 177.3 145.7 115 161 115 115
10
Colloidal silicon
dioxide(Aerosil200) 2 2 2 2 3.1 2.6 2.6 2.6 2.6 2.6
11 Magnesium stearate 3.6 3.6 3.6 3.6 5.6 4.6 4.6 4.6 4.6 4.6
Total wt of core tablet 360 360 360 360 560 460 460 460 460 460
Coating solution
12
Instacoat Universal brown
A0G11058IHS 10.8 10.8 10.8 10.8 16.8 13.8 13.8 13.8 13.8 13.8
13 Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s
Total wt of coated tablet 370.8 370.8 370.8 370.8 576.8 473.8 473.8 473.8 473.8 473.819

20. Sifting Dry Mixing
Binder
Preparation
Granulation
DryingSifting
Pre-
Lubrication
Lubrication
Compression Coating
20

21. b) In-Process
Evaluations of Tablet
1)Tablet
appearance
2)Weight
Variation
3)Hardness
4)Thickness5)Friability
6)Dissolution
7) Assay
21

22. on the basis
presence of pH
dependent
polymer
Formulation
were modified
with subject to
pH independent
polymer
concentration of
polymer and
surfactant were
changed
the capacity
of a drug
substance to
maintain its
identity,
quality and
purity
Definition
• quality of
the drug
substance
• shelf life
for drug
substance
Objective
• 1st and 2nd
month
Stability
testing
• assay
and% drug
release of
optimized
batch was
compared
Method
22

23.  Preformulation
Sr.No
.
Tests Specification Results
1 Description
Yellow crystalline
powder
Yellow crystalline
powder
2 Solubility
Soluble in ethanol and
insoluble in water.
Complies
3 Water content(%w/w) Not more than 0.50 0.15%
5 Assay (%w/w)
Not less than 99.0 &
Not more than101.0
96.9
6 Bulk Density (gm/ml) - 0.19
7 Tapped Density (gm/ml) - 0.334
8
Compressibility Index
(%)
- 42.42
9 Hausner ratio - 1.7
23

24. Sr.
No. Contents
Physical
Description Initial
Condition – Dry
40C/75% RH
15days 1months
1 API
Yellow crystalline
powder
No Change No Change
2
API+ Hypromellose (Methocel prem
K100LV)
Light yellow
crystalline powder
No Change No Change
3
API+ Lactose
monohydrate(pharmatose 200M)
Light yellow
crystalline powder
No Change No Change
4
API+ Methacrylic Acid Copolymer
(Eudragit L10055)
Light yellow
crystalline powder
No Change No Change
5
API+ Microcrystalline
cellulose(Avicel PH101)
Light yellow
crystalline powder
No Change No Change
6
API+ Sodium lauryl
sulphate(Texaponk12pPH)
Light yellow
crystalline powder
No Change No Change
7
API+ Hypromellose(Methocel
K100CR)
Light yellow
crystalline powder
No Change No Change
8
API+ Colloidal silicon
dioxide(Aerosil 200)
Light yellow
crystalline powder
No Change No Change
9 API+ Magnesium stearate
Light yellow
crystalline powder
No Change No Change
10
API+ Instacoat Universal brown
A0G11058IHS
Dark yellow
crystalline powder
No Change No Change
11 API+ All Excipients
Light yellow yellow
crystalline powder
No Change No Change
Drug –Excipient Compatibility study
24

25. Trial
Evaluation Parameters
LOD at105ºC
(%) BD(gm/cm3) TD(gm/cm3) CI (%)
HR
F1 3.34 0.503 0.711 29.231 1.413
F 2 3.99 0.407 0.550 26.0 1.351
F 3 3.10 0.315 0.530 26.80 1.355
F4 2.55 0.350 0.533 25.23 1.315
F 5 3.75 0.295 0.404 26.923 1.368
F6 3.25 0.326 0.439 25.714 1.346
F 7 3.41 0.321 0.411 21.875 1.280
F 8 3.48 0.406 0.515 21.212 1.269
F9 3.45 0.340 0.451 24.59 1.326
F10 3.46 0.320 0.423 25.21 1.319
Characteristics of Lubricated Blend
25

26. Formula
optimization
Trial without
pH
dependent
polymer
Trials with
pH
dependent
polymer.
Optimization
of effective
drug release
surface area.
Optimization
of HPMC
Optimization
of MCC and
Lactose
ratio.
Final
optimized
formula
26

27. Trials
Evaluation Parameters of Uncoated Matrix tablet
(without pH dependant )
Av.w (Mg) Thick (mm.) Hardness (N) Friability (%)
F1 360 5.45 138 0.04
F 2 361 5.28 142 0.06
Dissolution in (0.1 N HCL+0.5% SLS), paddle 50 rpm, 900ml
Time
(Hrs)
% Drug Release
Sular F1 F2
1 2 1 4
2 7 1 9
4 20 2 20
6 32 22 32
8 39 40 43
10 57 45 57
12 74 59 68
15 78 75 80
16 87 83 89
18 90 86 90
20 91 88 98
24 95 92 97
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRelease
Time(Hrs)
% Drug Release inHCL+0.5%SLS
Sular F1 F2
27

28. Time (Hrs) % Drug Release
Sular F2
1 4 4
2 12 10
4 30 21
6 47 29
8 62 42
10 80 53
12 90 62
15 92 73
16 94 80
18 93 85
20 93 90
24 95 94
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRelease
Time(Hrs)
%Drug Release in pH6.8 +0.5 % SLS
Sular F2
Dissolution in ph 6.8 +0.5 % SLS, paddle, 50 rpm, 900 ml
28

29. Trials
Evaluation Parameters of Uncoated Matrix tablet
( pH dependant )
Av.wt(Mg)
Thickness
(mm.)
Hardness
(N)
Friability
(%)
F3 360 5.10 138 0.03
F4 361 5.07 145 0.04
% Drug Release in HCl+0.5%SLS.
Time (Hrs) % Drug Release
Sular F3 F4
1 2 4 1
2 7 12 3
4 20 23 13
6 32 38 22
8 39 46 32
10 57 62 49
12 74 80 64
15 78 89 72
16 87 95 79
18 90 97 84
20 91 98 88
24 95 98 92
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRrelease
Time(Hrs)
% Drug Release inHCL+0.5%SLS
Sular F3 F4
29

30. % Drug Release in pH 6.8+0.5%SLS
Time
(Hrs) %Drug Relesase
Sular F3 F4
1 4 5 5
2 12 21 12
4 30 40 28
6 47 52 45
8 62 73 60
10 80 94 74
12 90 94 83
15 92 96 91
16 94 98 93
18 93 100 96
20 93 100 96
24 95 100 97
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRelease
Time(Hrs)
% Drug Release in pH 6.8+%0.5%SLS
Sular F3 F4
30

31. Trials
Evaluation Parameters of Uncoated Matrix tablet
(Optimization of effective drug release surface area.)
Av.wt. (Mg)
Thickness(m
m.)
Hardness
(N)
Friability
(%)
F4 361 5.07 145 0.04
F5 560 6.54 175 0.11
F6 460 5.50 178 0.20
Time (Hrs)
% Drug Release
Sular F4 F5 F6
1 2 1 3 3
2 7 3 8 9
4 20 13 18 22
6 32 22 29 35
8 39 32 38 43
10 57 49 47 53
12 74 64 56 71
15 78 72 68 82
16 87 79 74 91
18 90 84 79 95
20 91 88 84 97
24 95 92 92 100
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRelease
Time(Hrs)
% Dug Release in HCL+0.5% SLS
Sular F4 F5 F6
% Drug Release in HCl+0.5%SLS.
31

32. Time
(Hrs)
% Drug Release
Sular F4 F5 F6
1 4 5 7 6
2 12 12 14 15
4 30 28 31 35
6 47 45 52 53
8 62 60 59 68
10 80 74 73 82
12 90 83 79 93
15 92 91 88 95
16 94 93 92 95
18 93 96 93 96
20 93 96 95 97
24 95 97 95 98
32
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRelease
Time(Hrs)
% Drug Release in pH 6.8+%0.5%SLS
Sular F4 F5 F6
%Drug Release in pH 6.8 +0.5 %SLS

33. Trials
Evaluation Parameters of Uncoated Matrix tablet)
(Optimization of HPMC)
Av.wt. (Mg)
Thickness(m
m.)
Hardness
(N)
Friability
(%)
F6 460 5.50 178 0.20
F7 460 5.45 179 Nil
F8 460 5.51 175 0.22% Drug Release in 0.1N HCL+0.5% SLS.
Time
(Hrs)
% Drug Release
Sular F6 F7 F8
1 2 3 4 3
2 7 9 11 8
4 20 22 23 17
6 32 35 35 28
8 39 43 44 35
10 57 53 57 53
12 74 71 75 62
15 78 82 83 72
16 87 91 92 76
18 90 95 94 81
20 91 97 96 85
24 95 100 98 88
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRelease
Time(Hrs)
%Drug Release in HCL+0.5% SLS
Sular F6 F7 F8
33

34. %Drug Release in pH 6.8 +0.5 % SLS
Time
(Hrs)
% Drug Release
Sular F6 F7 F8
1 4 6 6 2
2 12 15 15 8
4 30 35 32 26
6 47 53 50 39
8 62 68 66 57
10 80 82 85 72
12 90 93 93 80
15 92 95 96 83
16 94 95 96 85
18 93 96 95 82
20 93 97 94 82
24 95 98 97 86 0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRelease
Time(Hrs)
Dissolution in pH 6.8+0.5 % SLS
Sular F6 F7 F8
34

35. Trials
Evaluation Parameters of Uncoated Matrix tablet
(Optimization of MCC and Lactose ratio)
Av.wt. (Mg)
Thickness
(mm.)
Hardness
(N)
Friability
(%)
F7 460 5.45 179 Nil
F9 460 5.49 175 0.04
F10 460 5.51 169 Nil% Drug Release in HCL+0.5% SLS
Time (Hrs)
% Drug Release
Sular F7 F9 F10
1 2 4 8 2
2 7 11 15 8
4 20 23 29 21
6 32 35 42 33
8 39 44 52 40
10 57 57 64 55
12 74 75 83 74
15 78 83 90 80
16 87 92 95 88
18 90 94 99 90
20 91 96 100 93
24 95 98 100 99
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
%DrugRelease
Time(Hrs)
%Drug Release in(HCL+0.5% SLS)
Sular F7 F9 F10
35

36. % Drug Release in pH 6.8 +0.5 % SLS
Time
(Hrs)
% Drug Release
Sular F7 F9 F10
1 4 6 8 6
2 12 15 20 14
4 30 32 36 31
6 47 50 55 46
8 62 66 70 62
10 80 85 86 79
12 90 93 95 89
15 92 96 98 92
16 94 96 98 94
18 93 95 99 97
20 93 94 100 98
24 95 97 100 99
36

37. Evaluation
Parameters
High Hardness Low Hardness Optimum Hardness
Av.wt. (Mg) 461 460 460
Thickness (nm.) 5.40 5.61 5.59
Hardness (N) 181 120 169
Friability (%) 0.02 0.30 Nil
Assay of Formulation
% Labeled amount
Drugs Innovat
or
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
NSL 99.8 98.0 99.2 98.3 98.2 97.3 99.1 99.1 98.0 99.23 99.5
Stability study results
Parameter Initial
40°C / 75%RH
After 1 month After2 month
Description
Orange colored round shape
biconvex film coated tablet plain
on both side.
Complies Complies
Average Weight (mg) 460.0 459.9 459.9
Assay (%) 99.50 99.55 99.51
Evaluation of finally optimized formula

38. % Drug Release in 0.1 N HCL
Time
(Hrs)
% drug release
Initial 1month 2 months
1 2 2 2
2 8 7 8
4 21 21 21
6 33 34 34
8 40 41 41
10 55 56 56
12 74 75 75
15 80 81 81
16 88 88 89
18 90 90 90
20 93 94 93
24 99 98 99
38

39. Time
(Hrs)
% drug release
Initial 1month 2 months
1 6 6 6
2 14 14 14
4 31 32 31
6 46 47 46
8 62 63 63
10 79 79 79
12 89 89 90
15 92 93 92
16 94 94 94
18 97 97 97
20 98 98 98
24 99 98 99
% Drug Release in pH 6.8+0.5% SLS
39

40. 1)Compatibility
studies
2)Evaluation
of Blend
3)In Process
Evaluation
Tests for
Tablets
4)InVitro
Release Study
5)Stability
Study of
Optimized
Batch
40

41. Relatively well absorbed into the systemic
circulation with 87% of the radiolabeled
drug recovered in urine and feces
Suitable candidate for delayed/controlled
release matrix tablet
Market reference product explorted trilayer
tablet approach with inactive layer
sandwiching drug layer
Similar profile was achieved in trial
mention by using monolayer tableting
approach
Delayed release matrix tablet s best
promising option for drug get metabolized in
gut wall.
The role of ph dependent and independent
polymer enhance the flexibility and efficacy
of dosage form.
41

42.  Robinson, J.R., Lee, V.H.L., In, Controlled Drug Delivery: Fundamentals and Applications
(Robinson, J.R., Lee, V.H.L, ed.), 2nd edition. Marcel Dekker, New York, 1987, pag16.
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Prakashan; 2008, Pag335-371.
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Pharmaceutical And Chemical Sciences Apr – Jun 2012, vol. 1 (2).
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2002, pag.1-43.
42

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2011,pag143-151.
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ed,vallabh prakashan, 2002, pag 156-189
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Metformin Hydrochloride Using pH Dependent and pH Independent Methacrylate
Polymer, British Journal of Pharmaceutical Research2011 1(2),pag29-45.
 Mulani H, Development of pH-independent matrix type sustained release drug
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43

44. Thank You
44