Formulation and development of antihypertensive immediate release tablets

Formul
1
Formulation and Development of
Antihypertensive Immediate Release
Tablets Presented By: Anvita Jadhav
M. Pharm (IP)

Introduction
∂ Tablet is the most popular among all dosage forms.
∂ Immediate release tablets are those which rapidly disintegrate and get dissolved
to release the medicaments very quickly.
∂ The basic approach used in development immediate release tablets is the use of
superdisintegrants.
Dosage
Form:
Immediate
Release
Tablet
• Dose precision
• Compactness
• Ease of administration
• Rapid dissolution
• Quick onset of action
• Ease of shipping etc.
Advantages 2

Diuretics, ACE inhibitors,
Angiotensin-II receptor
antagonists, Calcium
channel blockers, β
adrenergic blockers, β + α
adrenergic blockers, α
adrenergic blockers, Central
sympatholytics &
Vasodilators
Clinical classification of hypertension
Category
Systolic
(mm Hg)
Diastolic
(mm Hg)
Optimal < 120 < 80
Normal < 130 < 85
High normal 130 – 139 85 – 89
Hypertension
mild (stage 1) 140 – 159 90 – 99
moderate (stage 2) 160 – 179 100 – 109
severe (stage 3) 180 – 209 110 – 119
very severe (stage 4) ≥ 180 ≥ 110
Very common disorder, particularly past middle age.
WHO – ISH guidelines have defined hypertension to be ≥140 mm Hg systolic and ≥90 mm Hg
diastolic.
Globally, complications of hypertension account for 9.4 million deaths worldwide every year.
Hypertension
3

Combination Therapy
• Almost 70% of hypertensive patients do not reach the
recommended treatment target of <140/90 mmHg with
monotherapy, therefore combination therapy necessary to
achieve these targets with minimal adverse effects.
Advantages
Combination of 2 agents at low
doses gives greater blood pressure
reductions than higher dose of 1
drug
Fewer adverse effects
Blockade of several pathways
that increase blood pressure
Prompt blood pressure control
Effects beyond their
antihypertensive actions
Double
Combination
• CCB + ARB/ACEI
• CCB + β blocker
• Diuretic+ ARB/ACEI
• Diuretic + β blocker
• β blocker + ARB/ACEI
Triple
Combination
• CCB+ ARB + Diuretic
• CCB+ RI + Diuretic
4

Ca++
L – type Ca++
channel
↑ Arterial
vasodilation
↓ BP
5
Angiotensin II
AT1
↓
Vasoconstriction
↓ BP
Calcium
Channel
Blocker
BCS Class I
Drug
A
Angiotensin
Receptor
Blocker
BCS Class II
Dru
g B
Additive BP lowering
10 mg 160 mg

6
6
Literature
Review
Preformulatio
n studies
Innovator
Characterization
Formulation
&
developme
nt of IR
tablets
Evaluation of
blend and
tablets
Stability
Studies
Optimization
Trials
Conclusio
n
Plan of work
Aim & Objectives
To formulate, develop and optimize immediate release tablets of combination of drug A
and drug B for the treatment of hypertension.
To match the dissolution profile of formulation with the innovator’s product.

Literature Review
• Books, research article, review articles,
scientific journals and patents etc.
7

999
Physicochemical Properties of Drug A
Properties Details
Description White to off white powder, light and temperature sensitive
Molecular Weight 567.1 g/mol
Solubility
Freely soluble in methanol, sparingly soluble in anhydrous
ethanol, slightly soluble in water and 2 - propanol
Partition Coefficient 2.22
Melting point 198°C – 202°C
Hygroscopicity Non Hygroscopic

10101010101010
UV Spectrum of Drug A
ƛmax = 236 nm

111111111111
Infrared Spectrum of Drug A

1212121212
Properties Details
Description White to off white powder
Molecular Weight 435.5 g/mol
Solubility
Freely soluble in methanol and anhydrous ethanol, sparingly
soluble in methylene chloride, insoluble in water
Partition Coefficient 5.8
Melting point 116°C - 117°C
Hygroscopicity Hygroscopic
Physicochemical Properties of Drug B

13131313
UV Spectrum of Drug B
ƛmax = 250 nm

141414
Infrared Spectrum of Drug B

1515
Bulk Density 0.317 g/ml
Tapped Density 0.435g/ml
Compressibility Index 27.12
Hausner’s Ratio 1.37
Angle of Repose 45.15⁰
Particle Size Distribution
D90 45.20µm
D50 12.09µm
D10 2.18µm
Bulk Density 0.408 g/ml
Tapped Density 0.671g/ml
Compressibility Index 39.19
Hausner’s Ratio 1.64
Angle of Repose 66.01⁰
Particle Size Distribution
D90 35.30 µm
D50 10.13 µm
D10 1.91 µm
Drug A Drug B
Bulk Characterization

16
Saturation Solubility mg/ml
Media Drug A Drug B
0.1N HCl 3.53 0.08
0.01N HCl 4.19 0.09
0.001N HCl 4.33 0.12
pH 4.5 Phosphate Buffer 2.06 2.94
Water 2.81 0.21
Saturation Solubility Study

171717
Ratio of Drug: Excipient
Lactose
(anhydrous)
MCC 112 Croscarmellose
Sodium
Colloidal
Silicon
Dioxide
Magnesium
Stearate
Opadry
Yellow
All Excipients
Drug A 1: 10 1: 10 1: 2 1: 0.2 1: 0.1 1: 0.8 1: 15
Drug B 1:1 1:1 1: 0.2 1: 0.1 1: 0.1 1: 0.1 1: 1.5
Drug A + Drug B 1: 16: 16 1: 16: 16 1: 16: 3 1: 16: 1.5 1: 16: 1.5 1: 16: 1.5 1: 16: 20
Schedule for withdrawal of vials
Condition Time points
Initial 0th day
40°C±2°C/75%±5% RH (Open Vials) 15 Days and 1 Month
40°C±2°C/75%±5% RH (Closed Vials) 15 Days and 1 Month
25°C±2°C/60%±5% RH (Open Vials) 15 Days and 1 Month
25°C±2°C/60%±5% RH (Closed Vials) 15 Days and 1 Month
Analysis results
confirmed that
excipients used
are compatible
with both drugs.
Drug - Excipients Compatibility Studies

1818
Innovator Characterization

19
Physical Characterization of Innovator
Description Yellow colored, oval shaped, film coated tablets
Strength (Drug A) 10 mg
Strength (Drug B) 160 mg
Individual Tablet Weight (mg) 330.1, 328.0, 327.8, 329.9, 331.0
Disintegration time 1 min 02 sec to 1 min 10 sec
Hardness (N) 185, 185, 181, 175 & 172
Tablet Dimensions (mm)
Length 13.24, 13.25, 13.27, 13.24 & 13.25
Breadth 5.11, 5.12, 5.12, 5.13. & 5.11
Thickness 4.49, 4.50, 4.51, 4.48 & 4.51

2020
Multimedia Dissolution Profile of Drug A
Time
(min)
% Drug Release
pH 6.8
Phosphate
Buffer
0.1 N HCl
pH 4.5
Phosphate
Buffer
0 0 0 0
10 68 60 35
15 76 70 45
20 80 75 54
30 86 80 57
45 90 84 63
60 95 90 68 0
20
40
60
80
100
0 10 20 30 40 50 60
%DrugRelease Time (min)
pH 6.8 Phosphate Buffer
0.1 N HCl

212121
Multimedia Dissolution Profile of Drug B
Time
(min)
% Drug Release
pH 6.8
Phosphate
Buffer
pH 4.5
Phosphate
Buffer
0.1 N HCl
0 0 0 0
10 75 42 8
15 87 50 10
20 95 57 12
30 97 63 14
45 98 72 19
60 100 85 25
0
20
40
60
80
100
0 10 20 30 40 50 60
%DrugRelease
Time (min)
0.1 N HCl

222222
Formulation & Development

23232323
Process Selection
Direct
Compressio
n
Poor flow
properties
of Drug B
Not
Suitable
Wet
Granulation
Drug A is
susceptible
to thermal
degradation
Not
Suitable
Dry
Granulation
Slugging
Roller
Compaction
Suitable

2424242424
Excipients Selection
Diluent
Lactose (anhydrous)
SuperTab 21 AN
Disintegrant
Croscarmellose Sodium
Ac-Di-Sol
Glidant
Colloidal Silicon Dioxide
Aerosil 200
Lubricant
Magnesium Stearate
Coating Agent
Opadry Yellow
Diluent
Microcrystalline Cellulose
Pharmacel 112

25252525
Ingredients %w/w
Intragranular
Drug A 4.33
Drug B 50
Lactose (anhydrous) 40.42
Croscarmellose sodium 4
Colloidal silicon dioxide 0.5
Magnesium stearate 0.5
Extragranular
Slugging parameters Specifications
Punch size and
description
18 mm, circular punches having
plain surface on upper and lower
punch.
Average weight About 1500 mg
Hardness 70 ± 10 N
Compression parameters Specifications
Punch size and
description
13.1 x 5.1, Oval shaped
punches having plain
surface on upper and lower
punch.
Average weight 320 ± 16 mg
Thickness 4.5 ± 0.3 mm
Hardness 120 – 150 N
Disintegration time NMT 1 min
Trial 1
Dry Granulation (Slugging)

2626262626
Slugs obtained were not uniform. Hard slugs were obtained
The flow of lubricated blend was very poor
Fine particles were more than granules.
Sticking was observed while compression.
The slugging process was not feasible for the product.

2727272727
Ingredients %w/w
Intragranular
Drug A 4.33
Drug B 50
Lactose (anhydrous) 39.67
Croscarmellose sodium 4
Extragranular
Coating
Opadry Yellow 2.5
Trial 2
Dry Granulation (Roller Compaction)
Roller compaction parameters
Cycle 1 2
Roller pressure (Ton) 6.1 0.5
Roller speed/rotations (RPM) 2.4 10
Flake/Ribbon thickness (mm) 2 2
Coating parameters
Inlet temperature 51⁰C - 54⁰C
Exhaust temperature 40⁰C - 45⁰C
Product bed temperature 35⁰C - 40⁰C
Pan RPM 6
Pump Speed 3 – 6

282828282828
Feasible process
Flakes obtained were easy to screen
Hard granules, Poor flow
During compression process tablet weight uniformity was
difficult to maintain. Due to poor flow
acceptance value of content uniformity of drug A was more
than 15, hence it is not satisfactory.
f2 (drug A) = 28 & f2 (drug B) = 31

292929292929
T3 T4
Ingredients %w/w
Intragranular
Drug A 4.33 4.33
Drug B 50 50
Lactose (anhydrous) 27.76 26.91
Croscarmellose sodium 3 4
Colloidal silicon dioxide 0.5 0.5
Magnesium stearate 0.5 0.5
Extragranular
Coating
Opadry Yellow 2.5 2.5
Trial 3 and 4
Roller compaction parameters
Cycle 1 2
Roller pressure (Ton) 4.0 0.5
Roller speed/rotations (RPM) 3.3 10
Flake/Ribbon thickness (mm) 2 2

30303030303030
Trial 3
• Soft granules
• Passable flow
• Acceptance value of
content uniformity of
drug A was below 15
• f2 (drug A) = 35
• f2 (drug B) = 45
Trial 4
• DT was lowered by
few seconds
• f2 (drug A) = 40
• f2 (drug B) = 64
• Physical binding of
drug A during
compaction process.

3131313131313131
T5 T6
Ingredients %w/w %w/w
Intragranular
Drug B 50 50
Extragranular
Drug A 4.33 4.33
MCC 112 10.76 10.76
Coating
Opadry Yellow 2.5 2.5
Trial 5 and 6
• Extragranular addition of Drug A
• Extragranular addition of MCC
112 instead of Lactose
(anhydrous)

32323232323232
Drug A
release was
comparable
with
innovator
Multimedia
dissolution
was
comparable
Weight
uniformity
Results
were
reproducibl
e
Multimedia
dissolution
was
comparable Formula
&
process
finalized
Trial 5 Trial 6

333333333333333333
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60
%DrugRelease
Time (min)
Drug A
Innovator
T2
T3
T4
T5
T6
0
10
20
30
40
50
60
70
80
90
0 10 20 30 40 50 60
%DrugRelease
Time (min)
Drug B
Innovator
T2
T3
T4
T5
T6
Comparative Dissolution Profiles
(Dissolution Media= pH 4.5 Phosphate Buffer)

34343434343434343434
(Dissolution Media= pH 6.8 Phosphate Buffer)
0
20
40
60
80
100
120
0 10 20 30 40 50 60
%DrugRelease
Time (min)
Drug A
Innovator
T5
T6
0
20
40
60
80
100
120
0 10 20 30 40 50 60%DrugRelease
Time (min)
Drug B
Innovator
T5
T6

3535353535353535353535
(Dissolution Media= 0.1 N HCl)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60
%DrugRelease
Time (min)
Drug A
Innovator
T5
T6
0
5
10
15
20
25
30
0 10 20 30 40 50 60
Drug B
Innovator
T5
T6

363636363636363636363636
Evaluation of Lubricated Blend
Compressibility
Index
Hausner’s Ratio Angle of Repose Flow Character
T1 32.45 1.46 56.21⁰ Very Poor
T2 27.58 1.40 48.55⁰ Poor
T3 24.12 1.31 46.78⁰ Passable
T4 23.15 1.30 40.89⁰ Passable
T5 19.61 1.24 39.23⁰ Fair
T6 19.61 1.24 37.34⁰ Fair

37373737373737373737373737
Evaluation of Tablets
Assay % Uniformity of Dosage Units (Acceptance Value)
Drug A Drug B Drug A Drug B
T2 100.1 98.2 15.3 10.2
T3 102.3 100.2 10.2 6.7
T4 98.1 99.6 8.7 4.6
T5 102.8 99.3 5.8 2.3
T6 99.7 100.2 4.1 2.7

38383838383838383838383838
Manufacturing Process
Dispensing
Sifting
All other ing#12 mesh
Mg. stearate #60 mesh
Blending (DCB)
All other ing
10 min,16 RPM
Lubrication (DCB)
Mg. Stearate
5 min,16 RPM
Compaction
Cycle1Flakes #16 mesh
Cycle 2 Flakes
#25mesh
Blending (DCB)
Granules +
Extragranular material
(# 40 mesh)
10 min,16 RPM
Lubrication (DCB)
Mg. Stearate #60 mesh
5 min,16 RPM
Compression
Coating
10 % Opadry Yellow
2.5 % Weight Gain

39393939393939393939
Process
Parameters
Compression
Film
Coating
Roller
Compacti
on
Inlet Temperature 54⁰C
Exhaust Temperature 40⁰C
Bed Temperature 35 - 40⁰C
Pan RPM 6
Pump Speed 5 Average weight 320 mg ± 16 mg
Thickness 4.50 mm ± 0.3 mm
Hardness 120 N ± 10 N
Disintegration time NMT 1 min
Cycle
Roller pressure
(Ton)
Roller speed (RPM)
1 4.0 3.3
2 0.5 10.0

41
Two reproducible batches
1 Month
&
3 Months
40°C ± 2°C/ 75%RH ± 5%
RH
&
30°C ± 2°C/65% RH ± 5%
RH
PVC/PVDC
blister ICH Q1A (R2)

42
Trial 7
Parameters Specifications Initial 40°C/75% RH 30°C/65% RH
1
Month
3
Months
1
Month
3
Months
Appearance
Yellow colored, oval
shaped, film coated
tablets
- NC NC NC NC
DT (secs) About 1 min 53 – 63 60 – 70 59 – 72 59 – 67 52 – 60
Assay %
Drug A
90.0% - 110.0%
100.6 100.1 99.9 100.0 98.4
Drug B 97.3 101.2 96.2 99.9 97.9
% Drug release
(at 30 min)
Drug A NLT 75% in 30 min 93 89 91 92 91
Drug B NLT 80% in 30 min 96 98 97 97 99

43
Trial 8
Parameters Specifications Initial 40°C/75% RH 30°C/65% RH
1
Month
3
Months
1
Month
3
Months
Appearance
Yellow colored, oval
shaped, film coated
tablets
- NC NC NC NC
DT (secs) About 1 min 51 – 62 62 – 73 63 – 67 58 – 67 62 – 69
Assay %
Drug A
90.0% - 110.0%
99.6 97.2 97.6 98.9 97.3
Drug B 100.7 98.2 99.3 100.4 99.6
% Drug release
(at 30 min)
Drug A NLT 75% in 30 min 90 94 93 91 92
Drug B NLT 80% in 30 min 90 90 90 90 90

45
Optimization
Formula
Optimization
Quantity of
Super
Disintegrant
Quantity of
Lubricant
Process Optimization
Compaction
Roller Pressure
Cycle 1 Cycle 2
Blending
Blending Time
Pre-
lubrication
Lubrication
Compression
Hardness

464646
Current Level Higher
Level
Lower
Level
Intragranular 4 % 5 % 3 %
Extragranular 2 % 3 % 1 %
DT Secs (core tablets) 24 – 30 19 – 23 38 – 45
DT Secs (coated
tablets)
59 – 67 49 – 58 77 – 82
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60
%DrugReleae
Time (min)
Drug A
T6
Higher level
Lower level
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60
%DrugRlease Time (min)
Drug B
T6
Higher level
Lower level
Optimization
Trial 1
Quantity of
Super
Disintegrant

474747
Current
level
Higher
level
Lower
level
Intragranular 0.5 % 0.75 % 0.25%
Extragranular 0.5 % 0.75 % 0.25 %
DT Secs (coated tablets) 59 – 67 54 – 69 58 – 63
Optimization
Trial 2
Quantity of
Lubricant
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60
%DrugRelease
Time (min)
Drug A
T6
Higher level
Lower level
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60
Drug B
T6
Higher level
Lower level

484848
Current
level
Higher
level
Lower
level
Roller Pressure 4.0 Ton 6.0 Ton 2.0 Ton
PSD
Cumulative % Retained
on# 60 mesh
59 67 -
Optimization
Trial 3
Roller Pressure
(Cycle 1)
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60
%DrugRelease
Time (min)
Drug A
T6 Higher level
0
10
20
30
40
50
60
70
80
90
0 10 20 30 40 50 60
Drug B
T6 Higher level

494949
Current
level
Higher
level
Lower
level
Roller Pressure 0.5 Ton 0.8 Ton 0.2 Ton
PSD
Cumulative % Retained
on# 60 mesh
61 63 59
Optimization
Trial 4
Roller Pressure
(Cycle 2)
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60
%DrugRelease
Time (min)
Drug A
T6
Higher level
Lower level
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60
Drug B
T6
Higher level
Lower level

505050
TL TC TR
ML MC MR
BL BC BR
Sampling Positions
Optimization
Trial 5
Pre-lubrication
blending time
Current
level
Higher
level
Lower
level
Blending Time 10 min 13 min 7 min
Blend uniformity (Drug A)
Mean 98.18 95.74 93.97
Relative standard
deviation
2.2% 1.9% 4.34%

515151
Optimization
Trial 6
Lubrication
blending time
Current level Higher level Lower level
Blending Time 10 min 13 min 7 min
Bulk density 0.5 0.5 0.512
Tapped density 0.652 0.645 0.625
Particle size distribution
Cumulative % retained on mesh no. 60
57 61 60
Blend uniformity (Drug A)
Mean 99.18 94.74 96.97
Relative standard deviation 1.5% 2.7% 3.0%

525252
Current
level
Higher level Lower level
Hardness 120 ± 10 N 150 ± 10 N 90 ± 10 N
DT Secs (coated tablets) 59 – 67 77 – 83 45 – 50
Friability % 0.02 0.01 0.18
Optimization
Trial 7
Hardness
0
10
20
30
40
50
60
70
80
0 10 20 30 40 50 60
%DrugRelease
Time (min)
Drug A
T6
Higher level
Lower level
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60
Drug B
T6
Higher level
Lower level

535353
The compatibility
studies showed that
the excipients used
in the formulation
have no interaction
with the drug.
The tablets of drug A
and drug B were
developed
successfully.
Dissolution profile
was found to be
almost similar to the
reference product.
The finalized batch
was found to be
stable during
stability studies.
Optimization trials
were carried out
successfully
Future Scope
Pilot plant studies
Rework if necessary
Development of
different strength
with the same
drugs.
Conclusion

54
• S. B. Jadhav, Vaishali Kadam and Vishal G. Rathod, Immediate Release Drug Delivery System: A Review, World Journal of
Pharmacy and Pharmaceutical Sciences, Pg. No. 545 – 558, 3(6), 2014.
• Kishor Salunke, Kiran Wale, Ishwar Gundecha, Mahesh Balsane, Priya Pande and Snehal Hase, Immediate Drug Release Dosage
Form: A Review, American Journal of Pharmatech Research, Pg. No. 190 – 212, 4(1), 2014.
• Shailesh K. Singh and Venkatesh Naini, Dosage Forms: Non-Parenterals, Encyclopedia of Pharmaceutical Technology, Informa
Healthcare USA, Pg. No. 988 – 1000, 3rd Edition, Vol. 2, 2007.
• Gilbert S. Banker and Neil R. Anderson, Chapter 11 – Tablets, Section III – Pharmaceutical Dosage forms, The Theory and Practice
of Industrial Pharmacy, Lea and Febiger, Pg. No. 293 – 345, 3rd Edition, 1987.
• Larry L. Augsburger, Albert W. Brzeczko, Umang Shah and Huijeong Ashley Hahm, Super Disintegrants: Characterization and
Function, Encyclopedia of Pharmaceutical Technology, Informa Healthcare USA, Pg. No. 3553 – 3566, 3rd Edition, Vol. 6, 2007.
• Larry L. Augsburger and Mark J. Zellhofer, Tablet Formulation, Encyclopedia of Pharmaceutical Technology, Informa Healthcare
USA, Pg. No. 3641 – 3651, 3rd Edition, Vol. 6, 2007.
• Norman Anthony Armstrong, Tablet Manufacture, Encyclopedia of Pharmaceutical Technology, Informa Healthcare USA, Pg. No.
3653 – 3671, 3rd Edition, Vol. 6, 2007.
• R. W. Miller, Roller Compaction Technology, Handbook of Pharmaceutical Granulation Technology, Informa Healthcare USA, Pg.
No. 99 – 150, Vol. 81, 1997.
References

• James A. Seitz, Shashi P. Mehta and James L. Yeager, Chapter 12 – Tablet Coating, Section III – Pharmaceutical Dosage forms,
The Theory and Practice of Industrial Pharmacy, Lea and Febiger, Pg. No. 346, 3rd Edition, 1987.
• Linda A. Felton, Film Coating of Oral Solid Dosage Forms, Encyclopedia of Pharmaceutical Technology, Informa Healthcare USA,
Pg. No. 1729 – 1734, 3rd Edition, Vol. 3, 2007.
• K. D. Tripathi, Chapter 40 Antihypertensive Drugs, Essentials of Medical Pharmacology, Jaypee Brothers Medical Publishers Pvt.
Ltd., Pg. No. 539 – 554, 6th Edition, 2010.
• Harsh Mohan, Chapter 20 The Kidneys and Lower Urinary Tract, Textbook of Pathology, Jaypee Brothers Medical Publishers Pvt.
Ltd., Pg. No. 708 – 711, 5th Edition, 2006.
• Suzanne Oparil, M. Amin Zaman, and David A. Calhoun, Pathogenesis of Hypertension, Annals of Internal Medicine, Pg. No. 761 –
776, 139, 2003.
• Section 2 Hypertension: The Basic Fact, A Global Brief on Hypertension, World Health Organization, Pg. No. 16 – 19, 2013.
• Alberto F. Rubio-Guerra, David Castro-Serna, Cesar I. Elizalde Barrera and Luz M. Ramos-Brizuela, Current Concepts in
Combination Therapy for The Treatment of Hypertension: Combined Calcium Channel Blockers and RAAS Inhibitors, Integrated
Blood Pressure Control, Pg. No. 55 – 62, 2, 2009.
• Xinhuan Wan, Panqin Ma and Xiangrong Zhang, A Promising Choice in Hypertension Treatment: Fixed-dose Combinations, Asian
Journal of Pharmaceutical Sciences, Pg.No. 1 – 7, 9, 2014.
55

56
Acknowledgements
Almighty God
My Family
Dr. Milind J. Bhitre
Vidya & Pradnya

Formulation and development of antihypertensive immediate release tablets

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