Palanisamy P et al.

IRJP 2011, 2 (12), 185-190

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(12), 2011

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY ISSN 2230 8407
Available online www.irjponline.com Research Article

FORMULATION AND EVALUATION OF EFFERVESCENT TABLETS OF ACECLOFENAC
Palanisamy P*
1
, Rabi Abhishekh
1
, D Yoganand Kumar
2

1
Vinayaka Missions College of Pharmacy, Vinayaka Missions University, Salem, Tamil Nadu, India
2
Trainee Research Associate, Pharmacokinetics/Biostatistics, Axis Clinicals Ltd, Hyderabad, Andhra Pradesh, India

Article Received on: 05/10/11 Revised on: 30/10/11 Approved for publication: 19/11/11

*E-mail: palanisamy2907@gmail.com

ABSTRACT
Recently, fast-dissolving drug delivery systems have started gaining popularity and acceptance as new drug delivery systems, because they are easy to administer and lead to
better patient compliance. Usually, elderly people experience difficulty in swallowing the tablet. Aceclofenac is a NSAID which has greater inhibitory action against the
inducible form of cyclooxygenase (COX-2) which is implicated in the inflammatory response against the constitutive form of this enzyme (COX-1) inhibition. 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 comprising a therapeutic agent, a granulating agent, a micro particulate effervescent
component 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.
Key Words: Effervescent Tablets, COX-1,COX-2 Aceclofenac.

INTRODUCTION
As per revised definition proposed to US FDA Effervescent tablet
is a tablet intended to be dissolved or dispersed in water before
administration. It generally contains in addition to active
ingredients, mixture of acids/acid salts (citric, tartaric, malic acid or
any other suitable acid or acid anhydride) and carbonate and
hydrogen carbonates (sodium, potassium or any other suitable alkali
metal carbonate or hydrogen carbonate) which release carbon
dioxide when mixed with water. Occasionally, active ingredient
itself could act as the acid or alkali metal compound necessary for
effervescent reaction. 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. The aim of this study is to develop and physico-
chemically evaluate the Effervescent Tablets of Aceclofenac. To
enhance the onset of action of Aceclofenac and increase the
solubility of Aceclofenac. To enhance the bioavailability of drug. To
achieve better patient compliance, To Avoid the First Pass
Effect,They should have satisfactory property, Tablet having the
greater bioavailability than other dosage form, The stability of
Effervescent tablets can be increased, The effervescent tablets
require strictly humid control area. The Effervescent tablets can not
be made in a normal area where the humidity and temperature
condition not maintained.
Fast onset of action. - Effervescent tablet have major advantage
that the drug product is already in solution at the time it is
consumed, thus the absorption is faster and more complete than with
conventional table faster absorption means faster onset of action
effervescent drug are delivered to the stomach at a pH that is just
right for absorption many medication travel slowly through the
gastrointestinal tract or have absorption that is hampered by food or
other drug. No need to swallow tablet - effervescent medications are
administered in liquid form so they easy to take as compared to
tablets or capsule the number of people who cannot swallow tablet
or who dislike swallowing tablet and capsule is growing with an
effervescent dosage form, one dose can usually delivered in just 3 or
4 ounces of water. 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. More portability - effervescent tablet is more easily
transported than liquid medication because no water is added until it
is ready to use. Improved palatability - drugs delivered with
effervescent base, taste better than most liquids, mixture and
suspensions superior taste masking is achieved by limiting
objectionable characteristics and complementing formulations with
flavor and fragrances. The effervescent tablet essentially include
flavoring so they taste much better than a mixture of non
effervescent powder in water moreover, they produce fizzy tablets,
which may have better consumption appeal than the traditional
dosage form.More consistent response - drugs delivered with
effervescent technology have predictable and reproducible
pharmacokinetics profile that are much more consistent than the
tablets or capsule.Accurate dosing - researchers have been shown
that effervescent tablets enhance the absorption of number of active
ingredients compared to conventional formulations. This is because
the carbon dioxide created by the effervescent reaction can enhance
active ingredient permeability due to an alteration of paracellular
pathway. the paracellular pathway is the primary route of absorption
of hydrophilic active ingredients in which the solutes diffuse into the
intercellular space between epithelial cells. it is postulated that the
carbon dioxide widens the intercellular space between cell which
leads to greater absorption of active ingredients (both hydrophilic
and hydrophobic).the increased absorption of hydrophobic active
ingredients could be due to the non polar carbon dioxide gas
molecules partition into cell membrane, thus creating an increased
hydrophobic environment, which would allow the hydrophobic
active ingredients to be absorbed.
Conventional tablets are often associate with slower onset of action
and also undergoes first pass metabolism. Effervescent tablet avoid
the first pass metabolism and also produce rapid onset of action.
Oral liquid also provide rapid onset of action but required carefully
handling.
MATERIALS AND METHODS
Aceclofenac was procured by Shri Krishna Pharmaceuticals
(India),Citric acid, Fumaric acid, Sodium Citrate, Sodium benzoate
was gifeted by (Thomas baker, Mumbai),Tartaric acid ,Sodium
Bicarbonate was gifted by (Lar Chamical, Mumbai), Polyethlene
Palanisamy P et al. IRJP 2011, 2 (12), 185-190
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(12), 2011
glycol-6000 was gifted by (Supreme Chemicals Mumbai),
Polyvinylpyrolidone-K-30 was gifted by (Nan hangs industrial
co.itd), Simethicone was gifted by (Nouveam exports pvt. Ltd. navi,
Mumbai), Acesulfame potassium was gifted by Shanghai fortune
way co.Ltd, Mumbai,India.
Preformulation
Preformulation is a branch of pharmaceutical sciences that utilizes
biopharmaceutical principles in the determination of
physicochemical properties of a drug substance. The goal of pre-
formulation studies is to choose the correct form of the substance,
evaluate its physical properties and generate a through
understanding of the materials stability under various conditions,
leading to the optimal drug delivery system. The pre formulation
study focuses on the physiochemical parameters that could effect the
development of efficacious dosage form. These properties may
ultimately provide a rationale for formulation design. Also it will
help in minimizing problems in later stages of drug development,
reducing drug development costs and decreasing products time to
market. It gives the information needed to define the nature of the
drug substance and provide framework for the drug combination
with pharmaceutical excipients in the dosage form.

Objective: The overall objective of Preformulation testing is to
generate information useful to the formulation in developing desired,
stable and bioavailable dosage forms.
Scope: The use of pre formulation parameters maximizes the
chances in formulating an acceptable, safe, efficacious and stable
product.
Pre formulation encompasses at least following tests: -
Determination of melting point
The melting point of Aceclofenac was determined by using
Thermocal melting point apparatus.

Solubility
Aceclofenac is practically insoluble in water, freely soluble in
acetone, soluble in alcohol.
Angle of Repose (qqqq)
The frictional force in a loose powder or granules can be measured
by angle of repose. Angle of repose is defined as the maximum
angle possible between the surface of a pile of the powder and
horizontal plane.

tan q = h / r
q = tan
-1
(h/r)
Where, q is the angle of repose
h is height of pile
r is radius of the base of pile
Table 1 Relationship between Angle of Repose (qqqq) and flow properties
Angle of repose (qqqq) (degrees) Flow
<25 Excellent
25-30 Good
30-40 Passable
>40 Very poor

Method
A funnel was filled to the brim and the test sample was allowed to
flow smoothly through the orifice under gravity. From the cone
formed on a graph sheet was taken to measure the area of pile,
thereby evaluating the flowability of the granules. Height of the pile
was also measured.

Bulk Density
Bulk density is defined as the mass of a powder divided by the bulk
volume. The bulk density of a powder depends primarily on particle
size distribution, particle shape, and the tendency of the particles to
adhere to one another.
Both loose bulk density (LBD) and tapped bulk density (TBD) were
determined. A quantity of accurately weighed powder (bulk) from
each formula, previously shaken to break any agglomerates formed
was introduced into a 25 ml measuring cylinder. After the initial
volume was observed, the cylinder was allowed to fall under its own
weight onto a hard surface from the height of 2.5 cm at 2 seconds
interval. The taping was continued until no further change in volume
was noted. LBD and TBD were calculated using following formula;
Weight of the powder
LBD = --------- (a)
Volume of the packing


Weight of the powder
TBD = ---------- (b)
Tapped volume of packing

Tapped Density
After measuring the bulk volume the same measuring cylinder was
set into tap density apparatus. The tap density apparatus was set to
300 taps drop per minute and operated for 500 taps. Volume was
noted as (Va) and again tapped for 750 times and volume was noted
as (Vb). If the difference between Va and Vb not greater than 2%
then Vb is consider as final tapped volume. The tapped density is
calculated by the following formula.
Tapped density = Weight of powder / Tapped volume
Percentage Compressibility
The compressibility index of the granules was determined by Carrs
compressibility index. Grading of the powders for their flow
properties according to Carrs Index is shown in.

Table 2 Grading of the powders for their flow properties according to Carrs
Index
Consolidation Index (Carr
%)
Flow
5-15 Excellent
12-16 Good
18-21 Fair to passable
23-35 Poor
33-38 Very poor
>40 Very Very poor

(%) Carrs Index can be calculated by using the following formula
TBD LBD
Carrs Index (%) = x 100 ----- (c)
TBD
Drug Excipients IR compatibility study
Compatibility study of drug with excipients were carried out by
keeping the drug and excipients at 40
o
c + 75% RH and observed
after every seven days for the physical observation and finalized
excipients were confirmed by IR studies. The pure drug and its
formulation along with excipients were subjected to IR studies. In
the present study, the potassium bromide pellet was employed using
Prestige 21 Shimadzu FTIR Spectrometer .






Palanisamy P et al. IRJP 2011, 2 (12), 185-190
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(12), 2011
Table 3 Composition of effervescent Tablets Aceclofenac (Dry granulation)
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9
Aceclofenac 100 100 100 100 100 100 100 100 100
Citric acid (anhydrus) 300 410 980 1245 980 980 980 1045 1045
Tartaric acid 210 120 520 545 1045 1045 1045 540 740
Ascorbic acid 200 210 - - - - - - -
Sodium bicarbonate 720 860 1480 1480 1480 1940 1480 1980 1980
Sodium carbonate 230 435 240 240 240 240 780 240 240
Sodium citrate - - 15 15 15 - - - -
Sodium benzoate - - 20 20 20 25 20 20 20
Mannitol - 220 - - - - - - -
PEG-6000 30 - - - - - - - -
PVP-K-30 15 20 20 60 - 60 115 80 100
Acesulphum potassium - - - - 20 20 20 20 25

Table 4 Composition of Effervescent Tablets Aceclofenac (Wet Granulation)
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9
Aceclofenac 100 100 100 100 100 100 100 100 100
Citric acid (anhydrus) 300 410 980 1245 980 980 980 1045 1045
Tartaric acid 210 120 520 545 1045 1045 1045 540 740
Ascorbic acid 200 210 - - - - - - -
Sodium bicarbonate 720 860 1480 1480 1480 1940 1480 1980 1980
Sodium carbonate 230 435 240 240 240 240 780 240 240
Sodium citrate - - 15 15 15 - - - -
Sodium benzoate - - 20 20 20 25 20 20 20
Mannitol - 220 - - - - - - -
PEG-6000 30 - - - - - - - -
PVP-K-30 15 20 20 60 60 115 80 100
Simethicone - - - 15 15 - 60 25 50
Acesulphum potassium - - - - 20 20 20 20 25

EVALUATION OF EFFERVESCENT TABLETS
Uniformity of thickness Test
The maximum thickness of the formulation was found to be 6.09
mm. The minimum thickness of the formulation was found to be 5.6
mm.
Hardness test
The hardness of the tablet was found to be 2.0 to 4.0 Kg/cm
2
.
Friability test
The maximum friability of the formulation was found to be 0.34%.
The minimum friability of the formulation was found to be 0.28%.
The % friability was less than 1% in all the formulations ensuring
that the tablets were mechanically stable.


Weight Variation Test
All the formulated (F1 to F9) tablets were passed weight variation
test as the % weight variation was within the IP limits of 5.0% of
the weight. The weights of all the tablets were found to be uniform
with low standard deviation values. The prepared formulation
complies with the weight variation test.
Tablet Disintegration Test
Disintegration time was found to be 82 to 120 sec from all
formulations, F6 has minimum in vitro Effervescent time, but its
hardness is not good so we select formula F8.
PH of the solution Test
PH of solution prepared putting tablets into water was affected by
storage condition due to liberation of CO2 .
Table 5 Evaluation Of The Powder Blend
Batch
Code
Bulk density Tapped density Angle of repose
Percent
Compressibility
F1 0.509 0.543 31.45 16.06
F2 0.565 0.546 30.45 14.85
F3 0.587 0.632 31.78 15.85
F4 0.543 0.587 25.98 15.96
F5 0.534 0.532 30.87 15.75
F6 0.578 0.654 31.64 16.84
F7 0.521 0.587 30.60 15.43
F8 0.576 0.598 28.98 15.65
F9 0.565 0.543 27.67 15.53












Palanisamy P et al. IRJP 2011, 2 (12), 185-190
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(12), 2011
STANDARD CURVE OF ACECLOFENAC
y = 0.0321x
R
2
= 0.9996
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0 2 4 6 8 10 12
CONCECTRATION
A
B
S
O
R
B
A
C
E
(
%
)
Linear
Table 6 Evaluation Of Tablet Parameter
Batch code
Thickness
(mm)
Hardness
(kg)
Friability

Weight
variation
Disintegration
Time(sec.)
ph of
solution
F1 5.6 5.00 FAIL PASS 120 7.22
F2 5.46 5.00 FAIL PASS 116 7.42
F3 5.65 5.00 FAIL PASS 98 7.56
F4 5.76 3.00 0.30 PASS 79 7.61
F5 5.92 3.00 0.34 PASS 82 7.67
F6 5.9 3.00 0.29 PASS 87 7.67
F7 5.97 2.00 FAIL PASS 82 7.71
F8 5.89 3.00 0.28 PASS 97 7.80
F9 5.88 3.00 0.30 PASS 107 7.91

Table 7 Observation Of Effervescent Tablet
Batch code Dry granulation Wet granulation
F1
Only half of the tablet was showing effervescence and
sticking problem also occurred.
Capping problem and less effervescence
F2 Sticking problem, less effervescence Capping problem and less effervescence
F3 Sticking problem, less effervescence Capping problem and less effervescence
F4 Sticking problem, less effervescence Very quick effervescence, the tablet surface was rough
F5
Tablet gives good effervescence, but the some particles
settle at the bottom of the solution, sticking problem also
occurred.
Tablet gave good effervescence solution become some
what clear and with less capping problem
F6
Tablet gives good effervescence but the tablet surface
found rough and sticking problem also 0cour
Tablet gives good effervescence but the capping also as
such.
F7
The tablet gives good effervescence, capping problem but
the some particles become settled down, the hardness also
not good
The tablet gives good effervescence, no capping
problem and the solution become found to be clear,
hardness of tablet not good
F8
The tablet found to be good hardness but the capping
problem somewhat occurs, solution found to be not clear
The tablet gives good effervescence; no capping
problem and the solution become found to be clear,
hardness of tablet also good compared to other batches.
F9
Tablet gives good effervescence, but the some particles
settle at the bottom of the solution, sticking problem also
occurred.
Tablet gives slow effervescent. The other properties
like hardness, appearance are satisfactory.

UV SPECTRA: Aceclofenac in 0.1 N Methanol shows maximum
absorption at 273 nm.
PREPARATION OF STANDARD CALIBRATION CURVE
OF ACECLOFENAC
Principle of the Aceclofenac exhibits peak absorbance at 273 nm in
0.1 methanol instrument used: jasco, UV spectrophotometer, Japan
model series-135.
Table 8 Standard Calibration curve
CONCENTRATION
(/ml)
ABSORBANCE
(nm)
1 0.032
2 0.064
3 0.098
4 0.129
5 0.166
6 0.193
7 0.222
8 0.255
9 0.288
10 0.320
Slope-0.0321
R
2
=0.9996






Standard Curve Of Aceclofenac











U.V. Spectrum Of Aceclofenac













Palanisamy P et al. IRJP 2011, 2 (12), 185-190
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(12), 2011

Table 9 In Vitro Dissolution Study
S.N.
Time
(min)

Absorbance(nm)
Conc. (g
/ml)
Amount
Present
in 900 ml
%Drug
Release
0 0 0 0 0 0
1 1 0.0317 0.988 89 89
2 2 0.0360 1.122 101.01 101.01
3 3 0.0367 1.146 103.21 103.21
4 4 0.0367 1.144 103.02 103.02
5 5 0.0366 1.143 102.89 102.89

Stability Studies
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.
The stability studies of formulated tablets were carried out at 40
o
C,
RH 75% and at room temperature for one month. The effects of
temperature and time on the physical characteristics of the tablet
were evaluated for assessing the stability of the prepared
formulations.

Table 10 Stability study Disintegration Time of Formulation F8, at 40
0
/75%RH
Parameter Initial After 15 day Afyer 30 day
Disintegration Time(min) 97 95 95

Table 11 Stability study of in-vitro dissolution for formulation F8, at 40
0
/75%RH
Time Initial After 15 days After 30 days
0 0 0 0
1 89.00 89.00 89.00
2 101.01 101.01 100.01
3 103.21 103.00 103.00
4 103.02 103.00 102.89
5 102.89 102.30 102.00

Table 12 Disintegration Time of Formulation F8, at Room Temperature
Parameter Initial After 15 day Afyer 30 day
Disintegration Time
(min)
97 96 95

Table 13 In-vitro dissolution for formulation F8, at Room Temperature
Time Initial After 15 days After 30 days
0 0 0 0
1 89.00 89.00 89.00
2 101.01 101.01 100.01
3 103.21 103.15 103.00
4 103.02 103.00 102.89
5 102.89 102.50 102.50

SUMMARY AND CONCLUSION
The study was undertaken with an aim to formulate effervescent
tablet of Aceclofenac. Aceclofenac act by reducing production of
prostaglandin which involved in pain and fever process, by
inhibiting the cyclooxygenase enzyme. In present work an attempt
has been made to formulate an effervescent tablet containing
immediate release Aceclofenac using various acids and bases.
The effervescent tablets were prepared by different techniques such
as Direct compression, Wet granulation. The prepared tablets were
evaluated for content uniformity and physical parameters. Capping
and sticking problems were observed by Direct Compression
Method. So the surface of tablets was not uniform. But with the help
of wet granulation technique the powder become free flowing and
the compression of the tablets so good as compared to the direct
compression. Capping and sticking problems by the direct
compression method is the reason behind the selection of the wet
granulation method. Wet granulation method provided the acids and
bases protections from the environmental moisture and by this
capping problem were reduced. At the time of manufacturing of
effervescent tablets humidity and temperature should be maintained,
strictly.
The effervescent tablets were formulated using different acids and
bases. PVP K30 as a binder and sodium benzoate as a lubricant were
used in formulation of effervescent tablets. There are nine
formulations that contain the Citric acid, Tartaric acid, Sodium
bicarbonate, and Sodium carbonate were formulated. These nine
formulations were evaluated for hardness, friability, and weight
variation, effervescent time.

Table 14 Parameter Of Formula No.
Parameters

F8
Disintegration time (sec.)

98
% Drug release within 1 min.
89


From the above summary it was concluded that, the effervescent
tablets of Aceclofenac can be formulated for quick analgesic and
antipyretic action by effervescence reaction using Citric acid
(24.88%), Tartaric acid (12.85%), Sodium bicarbonate (47.14%) and
Sodium carbonate (5.71%). gives the better effervescence. The PVP-
K-30 (1.904%)used as the binding agent. Sodium benzoate (0.5%)
as lubricating agent.
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Source of support: Nil, Conflict of interest: None Declared