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Srinath et al., IJPRD, 2011; Vol 3(3): 12; May 2011 (76 - 104)
[Research Article]
ABSTRACT
The oral dosage forms are the most popular way of taking medication despite
having some disadvantages like slow absorption and thus onset of action is
prolong. This can be overcome by administrating the drug in liquid from but,
many APIs have limited level of stability in liquid form. So, Effervescent Tablets
acts as an alternative dosage form. The tablet is added into a glass of water just
before administration and the drug solution or dispersion is to be drunk
immediately. The tablet is quickly broken apart by internal liberation of CO2 in
water due to interaction between tartaric acid and citric acid with alkali metal
carbonates or bicarbonates in presence of water. Due to liberation in CO2 gas,
the dissolution of API in water as well as taste masking effect is enhanced. The
advantages of effervescent tablets compared with other oral dosage forms
includes an opportunity for formulator to improve taste, a more gentle action on
patients stomach and marketing aspects. In present work an attempt has been
made to formulate an effervescent tablet containing immediate release of
paracetamol using various acids and bases. In present work we are used
different acids and bases in different concentration. In the preformulation study,
compatibility evaluation was performed which implies that drug; acids, bases
and other excipient are compatible with each other. The formulation of tablets
was done by using wet granulation as well as dry granulation in that technique
wet granulation which was found acceptable.The total nine placebo tablets were
prepared and evaluated for hardness, disintegration time, weight variation and
solubility. All the formulation shows hardness and weight variation with in limit
but the combination of citric acid (12.56%), tartaric acid (25.17%), sodium
bicarbonate (38.20%), sodium carbonate (6.41%) ,binding agent PVP-K-30
(2.94%) and sodium benzoate (0.52%). for the final formulation,(F7) Because
these ingredients shows the good effervescent reaction and has no problem in
capping and sticking like other formulation
Correspondence to Author
Mr. K.R.Srinath
Pulla Reddy Institute Of
Pharmacy, Dundigal, Medak,
Andha Pradesh, India
Email
palanisamy2907@gmail.com
Key Words
Mucoadhesion, bioadhesion,
oral mucosa, mucin.
INTRODUCTION
76
Effervescent tablet:
The oral dosage forms are the most popular way of
taking
medication
despite
having
some
disadvantages like slow absorption and thus onset of
action is prolong. This can be overcome by
administrating the drug in liquid from but, many APIs
have limited level of stability in liquid form. So,
effervescent tablets acts as an alternative dosage
form. The tablet is added into a glass of water just
before administration and the drug solution or
dispersion is to be drunk immediately. The tablet is
quickly broken apart by internal liberation of CO2 in
water due to interaction between tartaric acid and
citric acid with alkali metal carbonates or
bicarbonates in presence of water.
Effervescent Tablets
Due to liberation in CO2 gas, the dissolution of API in
water as well as taste masking effect is enhanced.
The advantages of effervescent tablets compared
with other oral dosage forms includes an opportunity
for formulator to improve taste, a more gentle action
on patients stomach and marketing aspects. To
manufacture these tablets, either wet fusion or heat
fusion is adopted. The tablets are compressed soft
enough to produce an effervescent reaction that is
adequately rapid. Water soluble lubricants are used
to prevent an insoluble scum formation on water
surface. To add sweetness to the formulation,
saccharin is added since sucrose is hygroscopic and
add too much of bulk to the tablet. The
manufacturing shall be done under controlled
climatic condition to avoid effervescent reaction. The
packaging is done under 25% RH at 25C. Hands of
the consumers and atmospheric moisture after
Available online on www.ijprd.com
77
* Good stomach and intestinal tolerance effervescent tablet dissolve fully in a buffered
solution. Reduced localized contact in the upper
gastrointestinal tract leads to less irritation and
greater tolerability.buffering also prevent gastric acids
from interacting with drug themselves, which can be a
major cause of stomach.
78
solid-state stability
excipient compatibility
consideration in effervescent tablets formulation:
there are several factors, which influence the release of
drug from effervescent tablets.
particle size
dose
solubility
Category
Citric acid
acidifying agent
Tartaric acid
acidifying agent
Fumaric acid
acidulant
Ascorbic acid
antioxidant
Sodium bicarbonate
alkalizing agent
Sodium carbonate
alkalizing agent
Polyvinylpyrollidone-30
binding agent.
Polyethylene glycol-6000
binding agent
Mannitol
binding agent
Sodium citrate
buffering agent
lubricant
Sodium benzoate
lubricant
Acesulfum potassium
sweetener.
1.
2.
3.
4.
5.
6.
7.
i. Bulk Characterization
crystallinity, polymorphism and hygroscopicity
powder properties (flow, compaction, density,
particle size, surface area etc.)
microscopy (morphology, particle characteristics)
molecular spectroscopy (ft-ir)
ii. Solubility Analysis
solubility.
ph solubility profile
common ion effect
thermal effect on solubility
solubilization
dissolution
iii. Stability Analysis
stability (heat, light, acid, base, oxidizer)
8.
9.
10
11
12
13
solution stability
Available online on www.ijprd.com
79
Tartaric acid
Fumaric acid
Ascorbic acid
Sodium bicarbonate
Sodium carbonate
Polyvinylpyrollidone-30
Polyethylene glycol-6000
Mannitol
Sodium citrate
Sodium lauryl sulphate
Sodium benzoate
Acesulfum potassium
A. Evaluation of Granules of PARACETAMOL
Angle of repose
Bulk density
Tapped density
Compressibility
I) EVALUATION OF GRANULES
The ideal characteristics of a tablet that make
it a popular and acceptable dosage form are
compactness, physical stability, rapid production
capability, chemical stability and efficacy. In general
above characteristics of tablet are dictated by the
quality of the granulation from which it is made.
Many formulation and process variables involved in
Available online on www.ijprd.com
Where, = Angle
80
III) FRIABILITY:
Roche friabilator
was used to determine friability of the tablets. Twenty
preweighed tablets were placed in the friabilator, which
was then operated for 100 revolutions. The tablets
were then dedusted and reweighed. The friability was
computed by following formula:
c = b - u x 100
b
where, b = packed bulk density
F = 100 (1
Wo
81
TABLE NOS.NO.
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
34.37
231.63
15.92
ascorbic acid
200
13.75
sodium bicarbonate
277.86
19.10
sodium citrate
200
13.75
peg-6000
30
2.06
polyvinylpyrolidone-k-30
15
1.031
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
35.51
104.5
7.421
tartaric acid
201
14.27
sodium bicarbonate
352.5
25.03
polyvinylpyrolidone-k-30
18
1.27
18
1.27
aerosil
06
0.426
mannitol
208
1.477
82
FORMULA- 3
TABLE NO-5
S.NO.
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
34.86
citric acid(anhydrus)
104.5
7.28
tartaric acid
201
14.01
sodium bicarbonate
352.5
24.58
sodium carbonate
18
12.55
sodium citrate
20
1.394
mannitol
208
14.50
polyvinylpyrolidone-k-30
20
1.394
acesulphum potassium
10
0.697
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
11.83
520
12.30
tartaric acid
1045
24.73
sodium bicarbonate
1574
37.25
sodium carbonate
265
6.272
sodium benzoate
18
0.42
mannitol
208
4.92
polyvinylpyrolidone-k-30
60
1.42
acesulphum potassium
20
0.47
83
TABLE NO-7
S.NO.
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
12.48
485
12.11
tartaric acid
982
24.52
sodium bicarbonate
1483
37.03
sodium carbonate
250
6.24
sodium benzoate
10
0.24
mannitol
220
5.49
polyethylene glycol-
40
0.99
acesulphum potassium
20
0.48
6000
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
12.5
485
12.12
tartaric acid
982
24.55
sodium bicarbonate
1483
37.07
sodium carbonate
250
6.25
sodium benzoate
15
0.37
mannitol
225
5.62
polyvinyl pyrolidone-k-30
60
1.5
84
S.NO.
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
12.72
490
12.46
tartaric acid
982
24.98
sodium bicarbonate
1483
37.73
sodium carbonate
250
6.36
sodium benzoate
20
0.50
polyvinylpyrolidone-k-30
115
2.92
acesulphum potassium
30
0.76
TABLE
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
13.36
480
12.83
tartaric acid
970
25.93
sodium bicarbonate
1400
37.44
sodium carbonate
240
6.41
sodium benzoate
25
0.66
polyvinylpyrolidone-k-30
80
2.31
acesulphum potassium
20
0.53
85
S.NO.
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
13.53
480
12.99
tartaric acid
960
25.98
sodium bicarbonate
1350
36.53
sodium carbonate
210
5.68
sodium benzoate
30
0.81
polyvinylpyrolidone-k-30
100
2.70
acesulphum potassium
15
0.40
2) Base granulation
Wet Granulation: -
1) Acid granulation
86
FORMULA-1
TABLE NO-12
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
34.37
231.63
15.92
ascorbic acid
200
13.75
sodium bicarbonate
277.86
19.10
sodium citrate
200
13.75
peg-6000
30
2.06
polyvinylpyrolidone-k-30
15
1.031
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
35.51
104.5
7.421
tartaric acid
201
14.27
sodium bicarbonate
352.5
25.03
polyvinylpyrolidone-k-30
18
1.27
18
1.27
aerosil
06
0.426
mannitol
208
1.477
87
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
34.86
104.5
7.28
tartaric acid
201
14.01
sodium bicarbonate
352.5
24.58
sodium carbonate
18
12.55
sodium citrate
20
1.394
mannitol
208
14.50
polyvinylpyrolidone-k-30
20
1.394
acesulphum potassium
10
0.697
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
11.83
520
12.30
tartaric acid
1045
24.73
sodium bicarbonate
1574
37.25
sodium carbonate
265
6.272
sodium benzoate
18
0.42
mannitol
208
4.92
polyvinylpyrolidone-k-30
60
1.42
88
simethicone
15
0.35
10
acesulphum potassium
20
0.47
TABLE NO-16
S.NO.
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
12.48
485
12.11
tartaric acid
982
24.52
sodium bicarbonate
1483
37.03
sodium carbonate
250
6.24
sodium benzoate
10
0.24
mannitol
220
5.49
simethicone
15
0.37
polyethylene glycol-
40
0.99
10
acesulphum potassium
20
0.48
6000
Ingredients
QTY.(MG)
% W/W
paracetamol
500
12.5
485
12.12
tartaric acid
982
24.55
sodium bicarbonate
1483
37.07
sodium carbonate
250
6.25
sodium benzoate
15
0.37
89
mannitol
225
5.62
polyvinylpyrolidone-k-30
60
1.5
TABLE-18
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
12.72
490
12.46
tartaric acid
982
24.98
sodium bicarbonate
1483
37.73
sodium carbonate
250
6.36
sodium benzoate
20
0.50
polyvinylpyrolidone-k-30
115
2.92
simethicone
60
1.52
acesulphum potassium
30
0.76
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
13.36
480
12.83
tartaric acid
970
25.93
sodium bicarbonate
1400
37.44
sodium carbonate
240
6.41
sodium benzoate
25
0.66
polyvinylpyrolidone-k-30
80
2.31
90
simethicone
25
0.66
acesulphum potassium
20
0.53
INGREDIENTS
QTY.(MG)
% W/W
paracetamol
500
13.53
480
12.99
tartaric acid
960
25.98
sodium bicarbonate
1350
36.53
sodium carbonate
210
5.68
sodium benzoate
30
0.81
polyvinylpyrolidone-k-30
100
2.70
simethicone
50
1.35
acesulphum potassium
15
0.40
WET GRANULATION
F1
F2
F3
F4
Tablets
having
very
quick Tablets
having
very
quick
effervescence but the tablet surface effervescence,the
tablet
surface
found rough.
become smooth compaired to direct
compression.
91
F5
Tablet
gives
good
effervescence,solution
become
somewhat clear,not so much capping
problem.
F6
F7
F8
F9
92
concentration
mcg/ml
absorbance
0.022
0.044
0.064
0.087
0.115
0.135
0.157
0.180
0.206
10
slope=0.0229
0.240
r2=0.996
0.3
R2 = 0.9968
0.25
A b s o rb a n c e
0.2
0.15
0.1
0.05
0
0
10
12
concentration(mcg/ml)
EVALUATION OF TABLETS:
I) TABLET DIMENSIONS:
tablet dimension include thickness and diameter
of tablet. five tablet of each formulation were evaluated
and mean thickness values obtained are shown in table
no.-.
the value indicates that, die fill was uniform and
compression force was consistent.
II) FRIABILITY:
93
94
95
96
STABILITY STUDIES:
ACCELERATED STABILITY TESTING:
since the period of accelerated stability testing
can be as long as 3 months for the effervescent tablet.
therefore it is essential to devise a method that will
help rapid prediction of long-term stability of drug.
the accelerated stability testing is defined as
the validated method by which the product stability
may be predicted by storage of the product under
conditions that accelerate the change in defined and
predictable manner.
98%
97.7%
96%
97
0
1
2
3
5
INITIAL
AFTER 15 DAYS
100.15
100.1
99.91
99.29
95.76
95.84
94.22
94.53
104.5
102.45
99.24
99.15
TABLE NO.25- STABILITY PARAMETERS OF FORMULATION F7 STORED AT TEMPERATURE 40OC AND RH 75%.
AFTER
ONE
INITIAL
AFTER 15 DAYS
PARAMETER
MONTHS
Drug content (%)
98%
97.7%
96%
In-vitro disint. Time
65
70
(sec)
76
TABLE NO.26- STABILITY STUDY OF IN-VITRO DISSOLUTION FOR FORMULATION F7 STORED AT TEMPERATURE 40OC
AND RH 75%
PARAMETER
INITIAL
AFTER 15 DAYS
AFTER
MONTHS
104.5%
97%
98%
70
ONE
76
98
FD2
FD3
FD4
FD5
FD6
FD7
FD8
FD9
THICKNESS (MM)
5.60
5.39
5.49
5.95
5.90
5.85
5.85
5.88
5.83
DISINTEGRATION
TIME, SECONDS
% COMPRESSIBILITY
90
100
65
69
75
70
62
66
72
PROPERTY
FD2
FD3
FD4
FD5
FD6
FD7
FD8
FD9
PROPERTY
Bulk Density,
G/CM3
0.50
0.52
0.52
0.58
0.66
0.66
0.625
0.58
0.58
0.588
0.76
0.71
0.71
0.83
0.90
0.7142
0.66
0.66
14.96
31.57
26.76
18.30
20.48
27.67
12.50
13.13
13.13
Thickness (MM)
5.60
5.39
5.49
5.95
5.90
5.85
5.85
5.88
5.83
disintegration
TIME (SEC.)
90
100
65
55
59
70
62
66
72
water content
( l.o.d.) %
1.8
1.8
1.8
1.6
3.4
1.4
1.0
1.2
1.4
24.8
24.8
24.8
24.8
24.8
24.8
24.8
24.8
24.8
tapped density
G/CM3
%
Compressibility
DIAMETER (MM)
99
F1
F2
F3
F4
F5
F6
F7
F8
F9
paracetamol
500
500
500
500
500
500
500
500
500
231.63
104.5
525
520
485
485
490
480
480
tartaric acid
201
1045
1045
982
982
982
970
960
ascorbic acid
fumaric acid
191.96
sodium bicarbonate
277.86
352.5
1577
1574
1483
1483
1483
1400
1350
sodium carbonate
265
265
250
250
250
240
210
sodium citrate
200
20
sodium benzoate
18
10
15
20
25
30
208
208
208
220
225
40
60
115
80
100
mannitol
peg-6000
30
20
pvp-k-30
15
18
20
60
simethicone
15
15
60
25
50
acesulphum potassium
10
20
20
30
20
15
F1
F2
F3
F4
F5
F6
F7
F8
F9
paracetamol
500
500
500
500
500
500
500
500
500
231.63
104.5
525
520
485
485
490
480
480
tartaric acid
201
1045
1045
982
982
982
970
960
ascorbic acid
fumaric acid
191.96
100
sodium bicarbonate
277.86
352.5
1577
1574
1483
1483
1483
1400
1350
sodium carbonate
265
265
250
250
250
240
210
sodium citrate
200
20
sodium benzoate
18
10
15
20
25
30
208
208
208
220
225
40
60
115
80
100
30
20
15
mannitol
peg-6000
30
20
pvp-k-30
15
18
20
60
acesulphum potassium
10
20
20
TABLE NO.31-COMPARISON OF F7 FORMULATION WITH LEADING MARKETED SAMPLES I.E.ENO FRUIT SALT, HISTAC
TABLETS
FD7
0.625
0.7142
0.5882
0.7142
0.7692
0.666
% Compressibility
12.50
7.15
11.62
Hardness (kg/cm2)
3.9
4.7
Thickness (mm)
5.85
5.62
62
1.0
30
0.7
55
0.8
24.8
24.8
0.63g/tab(16.34%)
19%
16.23%
PROPERTY
Disintegration
time (sec.)
Water content
(l.o.d.) %
Diameter (mm)
Co2 content
102
103
16. L.Kalantzi,
C.Reppas,
J.B.
Dressman,
G.L.Amidon, H.E.Junginger in Journal of
Pharmaceutical Science 95,4-14.
17. Wikipedia of paracetamol.
18. Bernard Bannworth, Fabienne, in Drugs
2003, 2, 5-13.
19. Raymond C. Rowe, paul J. Sherskey,sain C.
owen.in Handbook of Pharmaceutical
excipients Ascorbic acid (2000), 48-50
20. Raymond C. Rowe, paul J. Sherskey,sain C.
owen.in Handbook of Pharmaceutical
excipients Fumaric acid (2000), 293-294.
21. Raymond C. Rowe, paul J. Sherskey,sain C.
owen.in Handbook of Pharmaceutical
excipients Citric acid (2000), 187.
22. Raymond C. Rowe, paul J. Sherskey,sain C.
owen.in Handbook of Pharmaceutical
excipients Tartaric acid (2000), 770-771.
23. Raymond C. Rowe, paul J. Sherskey,sain C.
owen.in Handbook of Pharmaceutical
excipients Sodium bicarbonate (2000), 665667.
24. Raymond C. Rowe, paul J. Sherskey,sain C.
owen.in Handbook of Pharmaceutical
excipients Sodium carbonate (2000), 668.
25. Raymond C. Rowe, paul J. Sherskey,sain C.
owen.in Handbook of Pharmaceutical
excipients Acesulfum potassium (2000), 4-5.
26. Raymond C. Rowe, paul J. Sherskey,sain C.
owen.in Handbook of Pharmaceutical
excipients Sodium banzoate (2000), 662-663.
27. Parikh P.M,Taylor and Francis Handbook of
Pharmaceutical granulation Technology 2nd
edition 154 New York 365-383.
28. Robert E Lece Amerilab Technology.
29. Eichman J.D and Robinson, J.R. Mechenistic in
Studies on Effervescent induced permeability
*****
104