In Vitro Evaluation of Commercially Available Enteric Coated Tablet

International Journal of Research in Pharmaceutical and Biomedical Sciences
ISSN: 2229-3701
__________________________________________Research Article
In vitro Evaluation of Commercially Available Enteric Coated Tablet

Containing Diclofenac Sodium
Tapan Kumar Giri*, Neha Parveen, Deepa Thakur, Amit Alexander, Ajazuddin,
Hemant Badwaik and Dulal Krishna Tripathi
Rungta College of Pharmaceutical Sciences and Research, Kohka Road, Kurud, Bhilai,
Chattisgarh, India.
_____________________________________________________________________________________
ABSTRACT
Diclofenac sodium is a well known representative of non-steroidal anti-inflammatory drugs, widely used to control
pain and inflammation of rheumatic and non-rheumatic origin. The purpose of this study was to determine the
pharmaceutical quality of the Diclofenac sodium tablets dispensed in India. Four different brands of Diclofenac
sodium tablets were purchased from pharmacies. The organoleptic and physicochemical properties of these
Diclofenac sodium tablets were assessed according to established methods. The results of weight variation,
thickness, diameter, hardness, friability, disintegration time, drug content and drug release of all marketed
products comply with established limit. The diclofenac tablet, B exhibited highest dissolution efficiency up to 10
minutes (15.36 0.213) compared to other tablets. However, tablet A showed highest % of drug content (99.425
0.27) compared to other tablets.
Key Words: Diclofenac sodium, analysis of variance, dissolution efficiency, disintegration time.
INTRODUCTION
Pain has been officially defined as an unpleasant
sensory and emotional experience associated with
actual or potential tissue damage. Pain acts as a
warning signal against disturbances of the body and
has a proactive function.1 NSAIDs are agents having
anti-inflammatory, analgesic and antipyretic effects.2
These drugs are used frequently and commonly in
humans as well as in animals to manage pain, fever
and inflammation for the treatment of different
clinical conditions such as rheumatic disorders,
musculo-skeletal disorders, sports injuries, muscular
cramps and other syndromes involving pain and
inflammation.2,3
These drugs have analgesic action at low dose and
anti-inflammatory action at high dose. As a class,
NSAIDs account for about 5% of all prescriptions in
Europe and United States.4 Many athletes self
administer NSAIDs prior to athletic participation to
prevent pain and inflammation before it occurs.5
Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAIDs) with analgesic and
antipyretic properties (Figure 1). It is widely used in
management of mild to moderate pain particularly
when inflammation is also present as in cases of
rheumatoid arthritis, osteoarthritis, musculoskeletal
injuries and some post operative conditions.6-8 Its
Vol. 3 (2) Apr Jun2012
pharmacological effects are believed to be due to

blocking the conversion of arachidonic acid to
prostaglandins by inhibiting cyclo-oxygenase
enzymes.9 The veterinary use of diclofenac sodium
has been limited to the catastrophic decline in South
Asian vulture population (95% plus since 1993).
These birds were exposed to diclofenac sodium when
scavenging on carcass of animal treated with
diclofenac. The scavengers had died due to renal
failure resulting from visceral gout related to relay
toxicity of diclofenac, the drug also affects
polymorphonuclear leukocyte function in vitro,
thereby reducing chemotoxins, superoxide toxic
radical formation, oxygen derived free radical
generation and neutral protease production.10,11
Diclofenac has been reported to suppress
inflammation in experimental animal models.12-14
Diclofenac sodium is almost completely absorbed
after oral administration. However, due to its firstpass metabolism, only about 50% of the absorbed
dose is systematically available.15-18 The half-life of
diclofenac sodium in plasma varies from 1-3 hours1921
, with mean peak plasma levels of approximately
0.5g/ml and 1.0 g/ml occurring after about two
hours after a single dose of 25mg and 50mg of
enteric coated tablets respectively. 22 About 99% of
www.ijrpbsonline.com
875
the drug is bound to human plasma proteins, mainly

albumin.23-24
In vitro testing or quality control of drugs is a set of
studies or experiments undertaken during production
in process and occasionally ought to be undertaken
post production by regulatory agencies and
researchers. Routine laboratory testing of drugs in the
market is a crucial to protect public health especially
in developing countries where counterfeit and
substandard drugs have become a major challenge to
health care services. The objective of this work was
therefore to evaluate the pharmaceutical quality of
some diclofenac sodium tablets dispensed in India.
MATERIALS AND METHODS
MATERIALS
Diclofenac sodium brands having label strength of
50mg (Table 1) were purchased from a retail
pharmacy. All tests were performed within product
expiry dates. The reagents potassium dihydrogen
phosphate, hydrochloric acid, sodium hydroxide were
obtained commercially and used as received.
METHODS
Weight Variation
Twenty tablets from each batch were collected
randomly and weight of individual tablet was
determined. The average weight of the twenty tablets
was calculated. Percentage deviation in weight of
each tablet from the average weight was
determined25.
Tablet thickness and diameter
Variation in the tablet thickness and diameter may
cause problems in counting and packaging in addition
to weight variation beyond the permissible limits.
Tablet thickness and diameter should be controlled
within a 5% of a standard value. Tablet thickness
and diameter was measured by Vernier caliper
(China).
Hardness
Tablet hardness was determined by Monsanto
hardness tester (Labtech, India). The reading was
noted. The reading indicates the hardness of the tablet
in kg/cm2.
Friability (%F)
20 tablets from each batch were selected randomly
and weighed. These preweighted tablets were
subjected to friability testing using Roche Friabilator
(India) for 100 revolutions. The tablet to the
combined effect of abrasion and shock in a plastic
chamber revolving at 25 rpm and dropping a tablet at
height of 6 inches in each revolution. Tablets were
removed, de-dusted and weighed again. The friability
ISSN: 2229-3701
of the tablets were calculated from the initial and

final weight and expressed in percentage. Friability
was not more than 1%. Following formula was used
to calculate the friability:
%F =
A B
100
A
Where, A =Iinitial weight of tablets, B = weight after

friability test.
In-vitro Disintegration Time
At random six tablets were selected from each brand
and place one in each of the tubes of the basket-rack
assembly of disintegration apparatus26. The assembly
was inserted in the simulated gastric fluid at 370C. At
the end of 120 mins, remove the basket-rack
assembly from the fluid and gently rinse with water.
Enteric coated tablets fail the test if any tablet show
distinct evidence of disintegration. Now replace the
simulated gastric fluid in the jar with simulated
intestinal fluid.
Preparation of standard calibration curve for
Diclofenac sodium in Phosphate Buffer (pH 6.8)
10mg of diclofenac sodium was taken in a 100ml
volumetric flask and volume was made upto the mark
by adding the buffer solution (pH6.8) . The solution
was used as a stock solution having a concentration
of 0.1mg/ml. Different concentrations of drug
solutions were prepared from stock solution.
Absorbance of the samples was taken at 276nm in a
spectrophotometer
(UV-1800
Shimadzu
UV
spectrophotometer) using phosphate buffer (pH6.8)
as blank. The average values of absorbance were
plotted against respective concentrations.
In-vitro Dissolution Study
In-vitro release of diclofenac sodium from the tablets
was studied in USP phosphate buffer solution(900ml,
pH6.8) at 370.50C and 100rpm using USP II
dissolution test apparatus (Electrolab- dissolution
tester USP TDL-08L). 5ml aliquot was removed from
the dissolution medium at specified time interval and
was replenished immediately with same volume of
fresh medium. Aliquots, following suitable medium,
were analysed spectrophotometrically at 276nm.
Drug content
The tablets were finely powered and a quantity of
powder equivalent to 100mg of diclofenac sodium
were accurately weighed and transferred to 100ml
volumetric flasks containing approximately 50ml of
buffer solution (pH6.8) and analysed for the content
of
diclofenac
sodium
using
UV-visible
876
spectrophotometer at 276nm. The drug content of

each sample was estimated from their previously
prepared standard curve.
Statistical analysis
By one-way analysis of variance the differences in
physicochemical properties were evaluated using
Graphpad Instart software. When P is < 0.05 the
differences were considered significant.
RESULT AND DISCUSSIONS
Four brands of diclofenac sodium tablets having 50
mg potency were purchased from local retail
pharmacy. All the brands of diclofenac sodium
tablets used were within their self life during the
study period. Weight variation, drug content,
disintegration time and dissolution are compendial
standards. Hardness and friability are referred to as
non compendia standards. However, friability is now
included in the United States Pharmacopeia (USP,
1995). Tablets were subject to weight variation study
(Table 2) for uniformity of weight. All brands
showed different mean weight which indicates the
use of different excipients in the different brands.
It is evident that the deviations from the average
weight are within limits in all brands since all brands
having uniform weight. Crown thickness and
diameter uniformity of tablets are necessary not only
for consumer requirements but also for packaging.
5% variation is permissible. The thickness and
diameter values of the branded tablets (Table 2) were
within limit.
The weight variation test is clearly not sufficient to
assure uniform potency of tablets. The potency of
tablets is expressed in terms of grams, milligrams, or
micrograms of drug per tablet and is given as the
label strength of the product. The BP specification is
that the content of drug should not be less than 95%
and not more than 105%. The potency of the tablets
was found to be 95.90 99.42% (Table 3). The result
ascertains the presence and compendia quantity of
diclofenac sodium in all the brands and so could not
be judged as counterfeits without active
pharmaceutical ingredients. However, statistically
significant difference (P < 0.05) of drug content was
observed in different tablet brands. The hardness of
the tablets is an essential criterion in the
determination of the ability of the tablets to resist
chipping, abrasion or breakage under conditions of
storage, transportation and handling. The hardness of
the tablet was found to be 2.5 5 kg/cm2 (Table 3).
Brand C required the least pressure before fracture
while brand A required highest pressure. The results
of the analysis of variance revealed significant
difference (P < 0.05) in hardness of all the four
brands at 95% confidence interval. Tablet hardness is
ISSN: 2229-3701
not an absolute indicator of strength since some

formulations, when compressed into very hard
tablets, tend to cap on attrition, losing their, crown
portions. Therefore, another measure of tablets
strength, its friability, is often measured.
Conventional compressed tablets that lose less than
1% of their weight are generally considered
acceptable. The friability of the tablets (determined
using Friabilator) was found between 0.012 0.102%
(Table 3) that was below 1% indicating sufficient
mechanical integrity and strength of the tablets.
Analysis of variance revealed significant difference
in friability (F calculated > F tabulated at 95% level) of
branded tablets.
For most tablets, the first important step toward
solution is breakdown or disintegration of the tablets
into smaller particles or granules. Various
formulations factors are known to affect
disintegration time of tablets. Disintegration time is a
necessary condition and could be the rate determining
step in the process of drug absorption. The type and
amount of excipients used in the tablet formulation as
well as the manufacturing process are all known to
affect the disintegration time of all tablets. The
disintegration time of enteric coated diclofenac
sodium 50mg tablets were determined according to
the procedure reported in USP (USP 2007). The
enteric coated tablets pass the disintegration test if
each of the six tablets does not disintegrates in 2
hours in the simulated gastric fluid and tablets should
disintegrate in not more than 60 minutes in the
simulated intestinal fluid. The results of the
disintegration test are presented in Table 4. The
results showed that all the brands passed the
disintegration test. However, analysis of variance
revealed significant difference in disintegration time (
F calculated > F tabulated at 95% level ) of branded tablets.
The drug release study is a measure of the amount of
the drug released into the dissolution medium with
time. This study gives an idea of amount of drug
available for absorption after oral administration.
Drugs with poor dissolution profile will not be
available in the body system to elicit therapeutic
effect. The results of dissolution tests in terms of
dissolution efficiency and time to dissolve 50% drug
(t50%) are collected in Table 5, whereas the
dissolution curves of diclofenac sodium tablets from
different manufactures are shown in Figure 3.
The dissolution efficiency (DE) is defined as the area
under the dissolution curve up to a certain time, t,
expressed as a percentage of the area of rectangle
described by 100% dissolution in the same time27.
877
y.dt
100%
DE = 0
y100 .t
Where y is the drug percent dissolved in time t.

DE can have a range of values depending on the
interval chosen. However, while comparing a set of
data a constant time interval should be selected. In
the present study, DE10 minutes (dissolution efficiency
ISSN: 2229-3701
up to 10minutes) were calculated from dissolution

profile of four brands of diclofenac sodium tablets
and used for comparison.
The time required for 50% ( t50%) of drug to be
released from four brands of tablets A, B, C and D
were 18.69, 17.47, 26.72 and 35.055 minutes
respectively ( Table 5). Moreover the DE also
follows the same trend with brands A, B, C and D
having 14.87, 15.36, 2.91 and 0.995% respectively.
Dissolution efficiency curves of tablets are presented
in Figure 4. From the dissolution efficiency profile, it
was observed that the dissolution efficiency increased
in the following order DCAB.
Table 1: Brands of Diclofenac sodium tablets used in the study

CODE
BRAND NAME
BATCH NO.
MFG. DATE
EXP. DATE
LABELLED
STRENGTH
Voveran50
MNB/07558
06/2011
05/2014
50mg
Relaxyl
3950.A
10/2010
09/2013
50mg
C
D
Dicloran
Vovo
G/820A
MNB/04/80
10/2010
03/2010
09/2013
02/2012
50mg
50mg
MANUFACTURER
Novartis India Ltd.
Baddi
Princeps Pharmaceutical Pvt. Ltd.,
Mumbai
Lekar Pharma Ltd., Ankleshwar
Alembic Ltd., Baddi
Table 2: Weight variation, thickness and diameter of diclofenac sodium tablets

Code
A
B
C
D
Weight (mg)
(MeanSD, n=20)
251.500.010
179.150.003
164.070.002
169.560.005
Thickness (mm)
(MeanSD, n=20)
3.600.052
3.190.048
4.700.053
4.640.049
Diameter(mm)
(MeanSD, n=20)
8.420.049
7.790.029
7.450.040
7.410.030
Table 3: Drug content, hardness and friability of diclofenac sodium tablets

Code
Drug Content (%)

(MeanSD, n=3)
99.4250.27
97.1510.84
98.1060.53
95.90.94
A
B
C
D
Hardness (Kg- cm2)

(MeanSD, n=3)
50.52
30.51
2.50.5
4.670.28
Friability(%)
(MeanSD, n=3)
0.01270.004
0.01280.006
0.01350.005
0.10200.070
Table 4: Disintegration time of Diclofenac sodium tablets

Disintegration Time in
simulated gastric fluid
Disintegration Time in
simulated intestinal fluid
No Disintegration after 120 min.
22 minutes
No Disintegration after 120 min.
25 minutes
No Disintegration after 120min.
23 minutes
No Disintegration after 120min
15 minutes
Formulations
878
ISSN: 2229-3701
Table 5: Characteristics of Diclofenac sodium tablets

Code
t50% (minutes)
DE10 (minutes)
A
18.09(0.337)
14.87(0.184)
B
17.47(0.370)
15.36(0.213)
C
26.72(0.069)
2.91(0.204)
D
35.055(0.255)
0.995(0.071)
Figures in parentheses indicate SD, n=3 for t50% and DE10 minutes.
Fig. 1: Structure of diclofenac sodium
Fig. 2: Calibration curve of Diclofenac sodium
Fig. 3: Dissolution profile of four brands of Diclofenac sodium tablets
879
ISSN: 2229-3701
Fig. 4: Dissolution efficiency of Diclofenac sodium tablets
CONCLUSION
The four brands of diclofenac sodium enteric coated
tablets evaluated in this study could be regarded as
being pharmaceutically and chemically equivalent
and can therefore be freely interchanged. Drug
content, hardness, friability, disintegration time and
dissolution profiles of all enteric coated products
used in the study were within specified limits. The
study also emphasized the need of constant
surveillance on marketed drug product by the
government, manufactures and independent research
groups to ensure supply and availability of quality
medicines for the patients.
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International Journal of Research in Pharmaceutical and Biomedical Sciences