International Journal for Pharmaceutical Research Scholars (IJPRS)
ISSN No: 2277-7873
RESEARCH ARTICLE
V-1, I-2, 2012
Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
Patel HK1*, Chauhan P, Patel KN, Patel BA, Patel PA
1
Shree Swaminarayan Sanskar Pharmacy College, Zundal, Gujarat-382421, India
Manuscript No: IJPRS/V1/I2/00078, Received On: 12/05/2012, Accepted On: 16/05/2012
ABSTRACT
Recently, fast-dissolving drug delivery system have started gaining popularity and acceptance as new
drug delivery system, because they are easy to administer and lead to better compliance. Usually, elderly
people experience difficulty in swallowing the tablet. Paracetamol having analgesic, antipyretic effect,
they inhibit cyclooxygenase enzyme involved in prostaglandin (PG) synthesis but not in peripheral
tissue while Ibuprofen inhibit prostaglandin (PG) synthesis in peripheral tissue so in this study
Paracetamol and Ibuprofen combination used for analgesic, anti-pyretic and anti-inflammatory action
simultaneously. The aim of this study was to formulate effervescent tablet with sufficient mechanical
integrity and to achieve faster disintegration in the water. Effervescent tablets are uncoated tablets that
generally contain acid substances and carbonates or bicarbonates and which react rapidly in the presence
of water by releasing carbon dioxide. They are intended to be dissolved or dispersed in water before use.
Effervescent compositions in the form of tablets are comprising a therapeutic agent, granulating agent,
and an effervescent system which dissolve rapidly in water to yield an effervescent solution containing a
completely dissolved therapeutic agent and a process for their preparation. In this study different ratio of
Citric acid and Sodium bicarbonate was used, superdisintegrant like SSG and cross-providone was used,
compared to cross-providone SSG decreases the Solution time of tablet. Granules prepared by Wet
granulation technique and from the result it was found that the Particle size 355-500 m of granules
show good Solution time and Hardness property.
KEYWORDS
Effervescent tablet, COX-1, COX-2, Paracetamol, Ibuprofen.
INTRODUCTION
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
*Address for Correspondence:
Hiren K. Patel
Department of Pharmaceutics,
Shree SwaminarayanSanskar Pharmacy College,
Zundal, Gujarat, India.
E-Mail Id: [email protected]
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interaction between Tartaric acid and Citric acid
with alkali metal carbonates or bicarbonates in
presence of water.1
Effervescent granules are usually prepared from
a combination of Citric acid and Tartaric acid
rather than from a single acid because the use of
either acid alone causes difficulties. When
Tartaric acid is the sole acid, the resulting
granules readily crumble and lack mechanical
strength. Citric acid alone results in a sticky
mixture which is difficult to granulate during
the manufacturing process.
Effervescent salts include the following
ingredients, which actually produce the
effervescence, Sodium bicarbonate, Citric acid
and Tartaric acid. When added to water the acid
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Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
and base react to liberate carbon dioxide,
resulting in Effervescence. It should be noted
that any acid-base combination which results in
the liberation of carbon dioxide could be used in
place of this combination as long as the
ingredients are suitable for pharmaceutical
use.The reaction between Citric acid and
Sodium bicarbonate and Tartaric acid and
Sodium bicarbonate, which results in liberation
of carbon dioxide, may be shown as follows:2,3
H3C6H5O7.H2O+ 3 NaHCO3
H2O +3 CO2
Na3C6H5O7 +4
Citric acid
Sodium bicarbonate Sodium
citrate Water Carbon dioxide
H2C4H4O6+ 2 NaHCO3
H2O + 2CO2
Na2C4H4O6 +
discs were prepared by compressing the
powders at a pressure of 5 tons for 5 min in a
hydraulic press. Forty scans were obtained at a
resolution of 4 cm-1, from 4000 to 400 cm-1.6,7
Drug-Excipients Compatibility Study by
DSC
The DSC study was carried out using DSC-60
(Shimadzu, Tokyo, Japan). The instrument
comprises of calorimeter, flow controller,
thermal analyzer and operating software. The
samples (drug and excipients) were heated in
sealed aluminum pans under nitrogen flow (30
ml/min) at a scanning rate of 5C/min from 50
to 300C. Empty aluminum pan was used as a
reference. The heat flow as a function of
temperature was measured for the samples.8,9
Tartaric acid Sodium bicarbonate Sodium
tartarate Water Carbon dioxide
PREPARATION OF CORE TABLETS
It should be noted that it requires 3 molecules of
Sodium bicarbonate to neutralize 1 molecule of
Citric acid and 2 molecule of Sodium
bicarbonate to neutralize 1 molecule of Tartaric
acid. The proportion of acids may be varied.
Usually it is desired that ratio of Citric acid to
Tartaric acid equals 1:2 so that the desired ratio
of the ingredients can be calculated as follows,
Wet Granulation: The Wet granulation process
performed into three steps
Citric
acid:
Tartaric
acid:
bicarbonate=1:2:3.44(by weight)4,5
Acid granulation
Sodium
MATERIALS AND METHODS
Paracetmol and Ibuprofen were obtained from
Acron Pharmaceutical Pvt. Ltd.(Ahmedabad,
India). Spray dried lactose was obtained from
Flumost
pharmaceuticals
(USA).
Other
ingredients used were of analytical grade.
DRUG - EXCIPIENTS COMPATIBILITY
STUDY
Drug-Excipients Compatibility Study by FTIR
Fourier-transform infrared (FT-IR) spectra were
obtained using an FT-IR spectrometer. The
Zaltoprofen and Excipients were previously
ground and mixed thoroughly with potassium
bromide, an infrared transparent matrix, at 1:5
(Sample: KBr) ratio, respectively. The KBr
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First method10,11,12
A) Dry Mixing & Granulation
B) Lubrication of Granules
C) Compression of Lubricated Granules
A) Dry Mixing & Granulation
In first step Weight the Citric acid, Tartaric acid
were blended and passed through Sieve No.40#.
In second step binding agent pvp-k-30 dissolved
in IPA.
The above Organic Solvent was mixed with
Acid portions i.e. Citric acid & Tartaric acid.
The obtained wet mass passed through sieve
no.20# & kept in tray dried at 600C for 1 hr.
Base granulation
In Base granulation firstly the Sodium
bicarbonate, Sodium carbonate were blended
and passed through sieve no.40#In the second
step the Binding agent pvp-k-30 was dissolved
in Organic solvent i.e. IPA. The above organic
solvent was mixed with Base portions i.e.
Sodium bicarbonate & Sodium carbonate. The
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Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
obtained wet mass passed through sieve no.20#
& kept in tray dried at 600c for 1 hr.
B) Lubrication of acid and base granules
After drying at Room Temperature of both
granules i.e. Acid granules and Base granules
were mixed.After mixing of both granules the
Paracetamol, Ibuprofen, flavour and Lubricating
agent like Sodium benzoate added to the
granules and well mixed.
C) Compression of Lubricated Granules
The Lubricated granules were compressed into
tablet by using rotary tablet punching machine.
(15mm punch)
Second method18
Drug (Paracetamol and Ibuprofen), Sodium
bicarbonate and Potassium carbonate were
blended & passed through sieve no. 40#,
granules prepared by using binding agent (8 ml
Water and 12 ml Ethanol) & dry at 60oC for 1
hr. Citric acid, Sodium bicarbonate, Magnesium
carbonate, spray dried lactose, SSG, PVP-K-30
and Sodium benzoate were blended and pass
through sieve no. 40#, granules prepared by
using binding agent (Ethanol) & dry at 60oC for
30 min. Both granules mix and dry at 60oC for
15 min. Granules were compressed into tablet
by using Single rotary tablet punching machine.
(15 mm punch)
EVALUATION PARAMETER
comprises of calorimeter, flow controller,
thermal analyzer and operating software. The
samples (drug and excipients) were heated in
sealed aluminum pans under air flow (30
ml/min) at a scanning rate of 20C/min from 50
to 300C. Empty aluminum pan was used as a
reference. The heat flow as a function of
temperature was measured for the samples.
POWDER FLOW PROPERTY
Angle of Repose13,14
The angle of repose of the mixture of the drug
and excipients was determined by fixed funnel
method. The values are used in the following
equation to get the angle of repose.
tan = h/r
Where, h, r and are the height, radius and
angle of repose of the powder pile.
Table 1: Relation of Angle of Repose with
Powder Flow
Angle of repose
Powder flow
< 25
Excellent
25-30
Good
30-40
Passable
40 >
Very Poor
FTIR study
Fourier-transform infrared (FT-IR) spectra were
obtained using an FT-IR spectrometer
(Shimadzu 8400S, Japan). The samples
(Zaltoprofen and Excipients) were previously
ground and mixed thoroughly with potassium
bromide, an infrared transparent matrix, at 1:5
(Sample:KBr) ratio, respectively. The KBr discs
were prepared by compressing the powders at a
pressure of 5 tons for 5 min in a hydraulic press.
Forty scans were obtained at a resolution of 4
cm-1, from 4000 to 400 cm-1.
Bulk Density and Tapped Density15
Accurately weighed of the sample was
transferred to the measuring cylinder of bulk
density apparatus and noted the volume as bulk
volume. The apparatus was adjusted for 100
tapping and noted the final volume as tapped
volume.
DSC study
Bulk density = mass of powder (w) / bulk
volume (Vb)
The DSC study was carried out using DSC-60
(Shimadzu, Tokyo, Japan). The instrument
Tapped density= mass of powder (w) / tapped
volume (V100)
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Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
Table 2: Composition of Batches F1-F9 by using Different Binding Agent
Ingredients
F1*
F2*
F3*
F4*
F5*
F6*
F7*
F8*
F9*
Ibuprofen
200
200
200
200
200
200
200
200
200
Paracetamol
325
325
325
325
325
325
325
325
325
Sodium bicarbonate
500
625
750
500
625
750
500
625
750
Citric acid(anhydrous)
250
250
250
250
250
250
250
250
250
Spray dried lactose
20
20
20
20
20
20
20
20
20
Magnesium carbonate
40
40
40
40
40
40
40
40
40
SSG
40
40
40
40
40
40
40
40
40
Sodium benzoate
20
20
20
20
20
20
Mannitol
Ethanol
2%
-
2%
-
2%
-
2%
2%
2%
PEG-6000
2%
2%
2%
F14*
F15*
F16*
F17*
200
325
525
250
100
20
40
40
20
2%
-
200
325
650
250
100
20
40
40
20
2%
-
200
325
700
400
100
20
40
20
20
2%
2%
200
325
850
400
150
20
40
20
20
2%
2%
*All values are expressed in mg/tablet
Table 3: Composition of Batches F10-F17
Ingredients
F10*
F11*
F12*
F13*
Ibuprofen
200
200
200
200
Paracetamol
325
325
325
325
Sodium bicarbonate
400
525
650
400
Citric acid(anhydrous)
250
250
250
250
Potassium carbonate
100
100
100
100
Spray dried lactose
20
20
20
20
Magnesium carbonate
40
40
40
40
SSG
40
40
40
40
Cross-providone
Sodium benzoate
20
20
20
20
Pvp-k-30
#
Pvp-k-30**& Ethanol
2%
2%
2%
#
Pvp-k-30**& Methanol
2%
#
Ethanol+Water**& Ethanol
#
*All values are expressed in mg/tablet, **Acid portion, Base portion
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512
Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
Compressibility Index16,17
The Carrs index of the powder was determined
by using formula:
Carrs index (%) = [(TBD LBD) 100]/TBD
Where, TBD is the total bulk density and LBD
is the loose bulk density.
Table 4: Relation of Carrs Index and Hausners
Ratio with Powder Flow
and analyzed by the use of UV Spectrometer at
340 nm.
Hardness
The hardness of the core tablets and coated
tables were measured using the Pfizer hardness
tester. Six tablets from each formulation were
randomly selected and used. The average
hardness and the standard deviation were
calculated. It is expressed in Kg/cm2.
Thickness
Carrs
Index
Flow
Characteristics
Hausners
Ratio
< 10
Excellent
1.00-1.11
11-15
Good
1.12-1.18
Thickness of the core tablets and coated tablets
were measured by using screw gauge. Ten
tablets from each formulation were randomly
selected and used. Thickness is expressed in
millimeters.
16-20
Fair
1.19-1.25
Friability test20
21-25
Passable
1.26-1.34
26-31
Poor
1.35-1.45
32-37
Very Poor
1.46-1.59
> 38
Extremely Poor
>1.60
Twenty tablets were weight and placed in the
Electrolab friabilator and apparatus was rotated
at 25 rpm for 4 min. After revolution the tablets
were de-dusted and weight. Percentage friability
was calculated from the loss in weight as given
in equation as below. The weight loss should
not be more than 1%.
Hausners Ratio
The Hausners ratio and Carrs index
aremeasures of the flow properties ofpowders.
A Hausners ratio of <1.25indicates a powder
that is free flowingwhereas >1.25 indicates poor
flow ability.
Solution time21,22
Hausners ratio = tapped density / Bulk density
The pH of solution can measured by pH meter,
pH of solution prepared by putting tablets into
water was affected by storage condition due to
liberation of CO2.
EVALUATION OF THE CORE TABLET
Weight Variation Test
Twenty tablets were randomly selected from
each batch and individually weighed. The
average weight and standard deviation of 20
tablets was calculated.
Content Uniformity18,19
Tablets were crushed in mortal and sufficient
amount of ethanol was added to dissolve
properly. Then appropriate dilution was done
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Time required for 2 tablets to dissolve in 180ml
of water at 17.5 2.5oC.
pH of the solution test23,24
Water content25,26
Titration method used to determine the water
content. In contrast to drying method, this is a
specific method if no side reactions occur only
water will be determined. While using drying
method some problem occurs like apart from
water, other volatile components of the sample
and decomposition products are also
determined. Titration method is rapid (few
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Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
minutes), can be validated & therefore fully
documented. With the Karlfischer (KF) titration
both free and bound water can be determined
e.g. surface water as crystals or the water
content inside them. The method works over a
wide concentration range from ppm upto 100%
and supplies reproducible and correct result.
Drug content
Formation of two simultaneous equations
were:
Set of two simultaneous equations were:
Cx = (A2 ay1 - A1 ay2)/ (ax2 ay1 - ax1 ay2)
and
Cy = (A1 ax2 - A2ax1)/ (ax2 ay1 - ax1 ay2),
Where
A1 and A2 are the absorbance of sample
solutions at 221.8 nm and 242.2 nm
respectively.
RESULT AND DISCUSSION
Interpretation of FTIR spectra
Compatibility studies were performed using
FTIR spectrophotometer. The characteristic
absorption peaks of pure drug and mixture with
other excipientswere obtained at different wave
numbers.
The peaks obtained in the spectra of pure drug
correlates with the peaks of drug with other
excipients. It does not show any major changes
in peaks which indicate no well-defined
interaction in drug and excipients spectrum.
This indicates that the drug is compatible with
the formulation components. The spectrum for
pure drug and excipients are shown in figure 1
to 4 and interpretations of spectrum are reported
in table no.5.
Cx and Cy are concentration of Ibuprofen and
Paracetamol in mg/mL in sample solution.
By substituting the values of A1 and A2 the
values of Cx and Cy can be calculated by
solving the two equations simultaneously. Here,
ax1 and ax2 are the absorptivity coefficient of
Ibuprofen at 221.8 nm and 242.2 nm
respectively; ay1 and ay2 are the absorptivity
coefficient of Paracetamol at 221.8 nm and
242.2 nm respectively.27,28
Estimation of Paracetamol and Ibuprofen in
Tablet:
Mix content of 20 Tablets and calculate the
average content weight of one tablet. Take
average weight of one tablet and make up the
volume of filtrate with Phosphate buffer
solution 7.2 pH. Filter this solution i.e. it
contains 325mg/100ml of Paracetamol and
200mg/100ml of Ibuprofen, this solution was
appropriately diluted to get approximate
concentration of 10g/ml. The absorbance of
sample solution was measured at 221.8 nm and
242.2 nm against blank. The content of
Paracetamol and Ibuprofen in tablet was
calculated using two framed simultaneous
equations.29,30
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Figure 1: FT-IR Spectrum of Paracetamol
Figure 2: FT-IR Spectrum of Ibuprofen
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Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
Drug-Excipients Compatibility Study by
DSC:
Figure 3: FT-IR Spectra of Paracetamol and
Ibuprofen Mixture
The DSC thermograms of pure drug and with
other excipients are depicted in Figure 6.13.
Here, pure drug has the melting point at 174
C&80oC for Paracetamol and Ibuprofen.
Mixture has the melting point at 187 C and 85
o
C. No change in the endotherm peak of the
drug was observed in the mixture of drug with
other excipients. From this, it was inferred that
there was no interaction between the drug and
excipients.23,24
Figure 4: FT-IR Spectra of Paracetamol and
Ibuprofen with all Formulation Excipients
Table 5: Interpretation of FT-IR Spectra21,22
Wave number (cm-1)
Group
Figure 5: Overlay DSC Thermogram of Pure
Paracetamol, Pure Ibuprofen and Physical
mixture
Paracetamol +
Ibuprofen
Physical
mixture
CH3 asymmetrical
stretching
2953.45
2955.38
O-HO stretching
combination
2360.44
2360.44
C=O stretching
1714.41
1714.41
The values obtained for angle of repose all (F1F17) formulations are tabulated in Table 6. All
formulation has value in the range of 25.37 to
39.17.This indicates good flow property of the
powder blends.
Amide II band
1509.03
1509.03
Density
CH-CO
deformation
1420.32
1428.99
OH in plane
deformation
1326.79
1326.79
C.C stretching
1227.47
1230.36
C-N-H group
1070.3
1070.3
Para-disubstituted
aromatic ring
1009.55
1011.48
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Angle of Repose()
a) Loose bulk Density(LBD)
The values obtained for loose bulk density of
(F1-F17) formulations are given in Table 6. The
maximum value of LBD was found to be 0.66
and minimum value was found to be 0.50 which
indicates good flow property. LBD value of all
(F1-F17) formulations ranges between 0.500.66.
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Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
b) Tapped density
The values obtained for tapped bulk density of
all (F1-F17) formulations are in Table 6. TBD
value of all (F1-F17) formulations ranges
between 0.59-0.79.
Hausners Ratio
The values obtained for Hausners ratio for all
(F1-F17) formulations are in Table. Hausners
ratio value of all (F1-F17) formulations ranges
between 1.12 - 1.26 indicating that the powder
blends have good flow property.
Carrs compressibility index
The values obtained for compressibility index
for all (F1-F17) formulations are tabulated in
Table. Compressibility index of all formulations
(F1-F17) was found between 10.81% - 20.77%
indicating that the powder blends have good
flow property.
Table 6: Evaluation of Powder blend (Batches F1-F17)
Formulations
Angle of
repose
()
Loose bulk
density
(LBD)
Tapped bulk
density (TBD)
Hausners
Ratio
Carrs
Compressibility
Index
(%)
F1
25.67
0.62
0.70
1.12
11.42
F2
27.06
0.64
0.72
1.13
11.11
F3
36.88
0.60
0.74
1.23
18.91
F4
29.74
0.54
0.62
1.15
12.90
F5
32.23
0.52
0.60
1.15
13.33
F6
29.82
0.55
0.63
1.14
12.69
F7
39.17
0.58
0.72
1.24
19.44
F8
39.53
0.61
0.77
1.26
20.77
F9
38.71
0.63
0.78
1.24
19.23
F10
26.82
0.61
0.69
1.13
11.59
F11
25.57
0.63
0.71
1.13
11.27
F12
28.31
0.58
0.66
1.14
12.12
F13
29.14
0.52
0.60
1.16
13.33
F14
26.87
0.55
0.62
1.13
11.30
F15
31.28
0.53
0.65
1.22
18.47
F16
25.37
0.62
0.70
1.13
11.42
F17
29.81
0.54
0.63
1.17
14.28
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Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
Table 7: Evaluation of Tablet (Batches F1-F9)
Formulations
Hardness
(kg/cm2)
Solution
time(second)
Friability
(%)
Content
uniformity(%)
pH of solution
F1
3.5
175
0.71
103*&105#
6.32
F2
4.0
155
0.60
91*&93#
6.11
F3
3.5
142
0.62
91*&97#
6.27
F4
3.0
117
0.85
94*&101#
6.35
F5
2.5
115
0.90
102*&92#
6.12
F6
2.0
117
0.80
99*&107#
6.93
F7
2.5
132
Fail
91*&97#
5.33
F8
2.5
135
Fail
104*&92#
5.47
F9
2.0
128
Fail
94*&101#
5.40
*Paracetamol, #Ibuprofen
Table 9: Evaluation of Tablet (Batches F10-F17)
Formulations
Hardness
(kg/cm2)
Solution
time
(second)
Friability
(%)
Content
uniformity (%)
pH of
solution
F10
3.1
130
0.80
98*&93#
7.00
F11
3.5
125
0.75
97*&98#
6.95
F12
3.2
127
0.81
97*&100#
7.10
F13
3.5
215
0.73
100*&107#
6.80
F14
4.0
187
0.65
104*&92#
7.05
F15
3.2
174
0.72
92*&92#
7.10
F16
4.5
133
0.30
98*&98#
7.18
F17
5.0
128
0.34
99*&97#
7.15
Water
Content
(%)
1.4
1
1.8
1
1
*Paracetamol, #Ibuprofen
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Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
CONCLUSION
a) In present work we are used different acids
and bases in different concentration from that
we conclude 1:2.5 ratio was excellent for this
formulation.
b) 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
(20.00%),
sodium
bicarbonate(42.5%),
potassium
carbonate(5.0%),
magnesium
carbonate(5.0%) for thefinal formulation, and
the binding agent PVP-K-30(2%) and sodium
benzoate (1%).because these ingredients
shows the good effervescent reaction and has
no problem in capping and sticking like other
formulation.
c) These formulations evaluated for hardness,
friability, and weight variation, solution time
etc. Formulation having acid base ratio 1:2
solution time found 125 to 135 second, ratio
1:2.5 solution time found 115 to 125 second
and ratio 1:3 solution time found 105 to 115
second, ratio 1:3 shows good solution time
but they hardness was found to be 2 to
3kg/cm2, while ratio 1:2.5 having harness 4
to 5kg/cm2 so acid base ratio 1:2.5 having
good Solution time, Hardness and other
parameters.
d) The effervescent tablets of Paracetamol and
Ibuprofen can be formulated for quick
analgesic, anti-pyretic action and antiinflammatory action by effervescence
reaction using citric acid (20%), sodium
bicarbonate (42.5%) and magnesium
carbonate (5.0%), potassium carbonate
(5.0%), pvp-k-30 (2%) gives the better
effervescence. The Ethanol used as the
binding agent. Sodium benzoate (1%) used as
lubricating agent.
e) Water content can be measured by Karl
Fischer titration method. Its values reveal that
content of moisture in tablet.
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f) The effervescent tablets were prepared by
wet granulation by using different binding
agent like pvp-k-30, mannitol, ethanol, peg6000 (also act as lubricant).
g) The prepared tablets were evaluated for
content uniformity and physical parameters,
while using peg-6000 and mannitol as
binding agent the solution time was low
compared to pvp-k-30 and ethanol.
h) When acid granulation and base granulation
performed separately hardness problem
occurs and Ibuprofen not soluble in a glass of
water at the time of taking medicines. To
overcome Ibuprofen solubility problem base
part granulate with drug i.e Paracetamol and
Ibuprofen using binding agent ethanol and
water, remaining part like acid, base,
lubricant granulate with ethanol in this part
pvp-k-30(2%) added in dry form, developing
formula by above method having good
evaluations parameters.
REFERENCES
1. Srinath KR, Chowdary P, Palanisamy P,
Vamsy K, Aparna S and Ali S, Formulation
and Evaluation of Effervescent Tablets of
Paracetamol. International Journal of
Pharmaceutical Research and Development,
2011, 2(12), 76-104.
2. Liberman H., Lachman L., Pharmaceutical
Dosage Forms: Tablets; Marcel Dekker Inc
New York, 1993, 85.
3. Liberman H., Lachman L., Pharmaceutical
Dosage Forms: Tablets; Marcel Dekker Inc
New York, 2005, 286-292.
4. Bolt I, Merrifield D and Carter P.
Pharmaceutical
Formulation
with
Effervescent
Couple.
U.S.
Patent
005962022, Oct. 5, 1999.
5. Pearlswig
D.M,
Masters
Thesis,
Simulation Modeling Applied to the Single
Pot Processing of Effervescent Tablets.
North Carolina State University, 1995.
6. Ali K, Effervescent Granules and Methods
for Their Preparation, May 2005,
518
Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
www.pharmainfo.net/reviews/reviewpatents-effervescent-granules.pdf
7. Parikh D., Handbook of Pharmaceutical
Granulation Marcel Dekker Inc. New York,
1997, 339.
8. Stahl H, Drying of Pharmaceutical
Granules in Single Pot Systems. Indian
Journal of Pharmaceutical Science. 1999,
7(61), 656-661.
9. Roscheisena G and Schmidt P, Preparation
and Optimisation of Leucine as Lubricant
for Effervescent Tablet Formulations.
Pharmaceutical Acta Helvetiae. 1995, 2(70),
133-139.
10. Rotthauser B, Kraus G and Schmidt P,
Optimization of Effervescent Tablet
Formulation Containing Spray Dried Lleucine and Polyethylene Glycol 6000 as
Lubricants using a Central Composite
Design. European Journal of Pharmaceutics
and Biopharmaceutics. 1998, 6(46), 85-94.
11. Van der Goten W, A Special Requirement
for Tablet Presses to be Used in
Effervescent Production. Technical Paper,
Halle, 2001.
12. Robert E, Lee M, Packaging of
Effervescent
Material,
2005,
www.amerilabtech.com/packaging/effervesc
entmaterial.
13. Ancel H., Popovich N. And Allen L.,
Pharmaceutical Dosage Forms and Drug
Delivery Systems; B. L. Waverly Private
Ltd, 1999, 469-471.
14. Howard L., Martin J., Harrisons Principles
of Internal Medicines; 16th Edn; McGrawhill Medical Publishing Division, 2005, 7175.
15. Lipsky P., Harrisons Principles of Internal
Medicines; 16th Edn; McGraw-hill Medical
Publishing Division, 2005, 1968-1970.
16. Arnett F, The American Rheumatism
Association 1987 Revised Criteria for the
Classification of Rheumatoid Arthritis.
Arthritis Rheum. 1988, 31, 315.
Copyright reserved by IJPRS
17. Choi H, Methotrexate and Mortality in
Patients with Rheumatoid Arthritis.
Clinical Therapeutics, 2002, 35, 160-173.
18. Gruber
P.
Effervescent
Ibuprofen
Preparation and Process for the Production.
U.S. Patent 0172981, Jul. 8, 2010.
19. Krishna S and Supanaranond W, Fever in
Uncompticated Plasmodium Falciparum
Malaria:
Randomized
Double-blind
Comparison of Ibuprofen and Paracetamol
Treatment. The Royal Society of Tropical
Medicine and Hygiene. 1995, 89, 507-509.
20. Livshits A, Machtinger R, David LB and
Spira M, Ibuprofen and Paracetamol for
Pain Relief During Medical Abortion: a
Double-blind
Randomized
Controlled
Study. Fertility and Sterility. 2009, 5(91),
1877-1880.
21. Kanabar D, Dale S and Rawat M,
Ibuprofen and Paracetamol Use in Febrile
Children and the Occurrence of AsthmaRelated Symptoms. Clinical Therapeutics.
2007, 12(29), 2716-2723.
22. Paul I, Sarah A, Yang C and Watts H,
Efficacy of Standard Doses of Ibuprofen
Alone, Alternating, and Combined with
Acetaminophen for the Treatment of Febrile
Children. Clinical Therapeutics. 2010,
14(32), 2433-2440.
23. Moore R, Straube S, Paine J, Derry S and
McQuay H, Minimum Efficacy Criteria for
Comparisons between Treatments Using
Individual Patient Meta-analysis of Acute
Pain Trials: Examples of Etoricoxib,
Paracetamol,
Ibuprofen,
and
Ibuprofen/Paracetamol Combinations after
Third Molar Extraction. International
Association for the Study of Pain. 2011,
152, 982989.
24. Helmy A, Kady S and Khames A,
Preparation, Characterization, and Invitro/vivo Evaluation of Indion-based
Chewable Tablets of Paracetamol and
Ibuprofen for Pediatric Use.Journal of
American Science. 2011, 7(12), 831-844.
519
Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen
25. Perioli L, Ambrogi V, Angelici F, Ricci M
and Giovagnoli S, Development of
Mucoadhesive
Patches
for
Buccal
Administration of Ibuprofen. Journal of
Control Release. 2004, 99, 73-82.
26. Pather L. Effervescent Drug Delivery
System for Oral Administration. U.S. Patent
6509036, Jan 21, 2003.
27. Gondalia R, Mashru R, Savaliya P,
Development
and
Validation
of
Spectrophotometric
Methods
for
Simultaneous Estimation of Ibuprofen and
Paracetamol in Soft Gelatin Capsule by
Simultaneous
Equation
Method.
International
Journal
of
ChemTech
Research. 2010, 2(4), 1881-1885.
Copyright reserved by IJPRS
28. Bolt J., Merrifield D. Pharmaceutical
Formulation with Effervescent Couple. U.S.
Patent 5962022, Oct 5, 1999.
29. Khoshayand M, Abdollahi H, Shariatpanahi
M and Saadatfard A, Simultaneous
Spectrophotometric
Determination
of
Paracetamol, Ibuprofen and Caffeine in
Pharmaceuticals by Chemometric Methods,
Spectrochimica Acta Part A. 2008, 70, 491
499.
30. Joshi R, Pawar N, Katiyar S and Devendra
B, Development and Validation of UV
Spectrophotometric
Methods
for
Simultaneous Estimation of Paracetamol and
Ibuprofen in Pure and Tablet Dosage Form.
Der Pharmacia Sinica. 2011, 2 (3), 164-171.
520
