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International Journal of Pharmaceutical Science and Health Care
Available online on http://www.rspublication.com/ijphc/index.html
Issue 4, Vol. 4. July-August 2014
ISSN 2249 – 5738
Comparative In-Vitro Evaluation of Different Brands of
Paracetamol Tablets Marketed in Maharashtra State
D. R. Jadge, A. N. Deshpande *, A. B. Gadgul, Y.A. Pandilwar, O. P. Patil
Dayanand College of Pharmacy, Latur, Maharashtra, India- 413 531
Mobile: +919890879742.
ABSTRACT:
Paracetamol tablets are popular OTC products among patients marketed by a lot of
suppliers around the world, being extensively used as antipyretic and general analgesic. The
purpose of this research work was to compare and evaluate quality standards in the various
brands of paracetamol tablets marketed in Maharashtra state. Six different brands of
paracetamol 500mg manufactured by multinational companies and local companies were
randomly sampled from different Pharmacy shops. The study was exclusively experimental
that used BP, USP and other official books to assess the in vitro quality of paracetamol tablet
using different analytical techniques and procedures. Evaluations of parameters were
performed through the determination of weight variation, hardness, friability, drug content,
and disintegration time and dissolution profile. All brands showed acceptable weight
variation and friability except one which was more fragile. Percentage content for analyzed
samples by UV method ranges from 92.32-102.2% indicating none of the brand contains less
than 92% of the active principle. The physical and chemical tests like in-vitro dissolution,
disintegration, hardness etc were found to be varying but within the specified limits. It can be
concluded that paracetamol brands of local companies are safe enough and could be used to
achieve desired therapeutic effects.
Keywords: Paracetamol,
Multinational brands.
Quality
Control
Parameters,
Evaluation,
Local
brands,
Corresponding Author: Mr. A. N. Deshpande
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International Journal of Pharmaceutical Science and Health Care
Available online on http://www.rspublication.com/ijphc/index.html
Issue 4, Vol. 4. July-August 2014
ISSN 2249 – 5738
1. INTRODUCTION:
The quality of pharmaceuticals is a global concern, counterfeit medicines are
increasingly detected worldwide.[1] Constant screening of marketed drugs by the drug
regulatory authority or a consumer organization, using pharmacopoeias method enables
consumer to be aware of the quality of drug. [2] Drug products that are chemically and
pharmaceutically equivalent must be identical in strength, quality, purity, active ingredient
release profile and should be in the same dosage form, for the same route of administration.
[3]
In order to ensure the requisite quality, drug manufacturers are required to test their
products during and after manufacturing and at various intervals during the shelf life of the
product. [4] As such the need to ensure that the generic and branded drugs products are
pharmaceutically equivalent cannot be overemphasized and the necessity to select one
product from several generic drug products of the same active ingredients is the cause for
concern. [5] When there is shortage in market of the multinational brand and some life saving
drugs, the patients are always reluctant to take the alternate local brands of same generic. If
the patient does so, he would not psychologically satisfy & ultimately results in poor patient
compliance. Some multinational brands are out of reach from buying due to high prices and
comparatively local brands of same generic are available at much lower prices. [6]
Paracetamol (4-hydroxy acetanilide) is a nonsteroidal anti-inflammatory drug
(NSAID) and is prescribed most frequently. The chemical structure of paracetamol is shown
in (Figure.1). It is widely used over the counter analgesic and antipyretic drug. [7] Generally it
is used to treat headache, other minor aches, pain and as in cold and flu remedies. It is also
useful in osteoarthritis therapy and management of cancer pain. When taken at recommended
doses it has an excellent safety profile, notably lacking the gastrointestinal side effects of
aspirin and ibuprofen, but overdoses of paracetamol can cause potentially fatal liver damage.
[8]
Tablet formulation of the drug product can have a significant effect on the quality
parameters such as weight variation, hardness, friability, disintegration time, dissolution
profile etc. and therapeutic effectiveness tablet relay on minimum of two factors, i.e. content
uniformity (the actual label claim) and its adequate bioavailability.[09] Depending upon these
facts, the present study was conducted to check, compare and prove the quality standards of
commercially available local pharmaceutical brands with that of multinational
pharmaceutical brands of paracetamol tablets marketed in Maharashtra as prescribed by B.P.
and U.S.P.
NH
CH3
O
HO
Fig. 1: Chemical Structure of Paracetamol
2. MATERIALS AND METHODS
2.1 Chemicals and Reagents
The reagents used were ferric chloride, Hydrochloric acid, potassium dichromate,
Sodium Hydroxide (Loba Chemie Pvt Co., India) all analytical grade reagent and freshly
deionised distilled water used throughout the work.
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International Journal of Pharmaceutical Science and Health Care
Available online on http://www.rspublication.com/ijphc/index.html
Issue 4, Vol. 4. July-August 2014
ISSN 2249 – 5738
2.2 Apparatus and Equipments
Double beam UV-Visible Spectrophotometer (Jasco 630), Analytical balance
(Shimadzu AUW220D), Hardness Tester (Monsanto, Mht-20), Tablet Friability Tester
(Roche, FTV-2), Disintegration apparatus (Electro Lab ED-2L), Dissolution apparatus
(Electro Lab, EDT-08LX ) Drying oven (Meta Lab.) and Ultrasonicator (Toshcon, SW 4).
2.3 Sample Collection
To perform the study paracetamol tablets of six different brands of multinational and
local companies were purchased from the pharmacy shops within Marathwada region and
coded as A, B, C, D, E and F respectively. All paracetamol brands were labeled to contain
500 mg of paracetamol per tablet. The commercial brands selected were of different
manufacturers. The labeled shelf life of all of the tablets was three years from the date of
manufacturing and was taken for the evaluation before two years of the labeled expiry date
(Table 1).
2.4 Study Design
Comparative in-vitro quality control parameters between commercially available local
pharmaceutical brands with that of multinational pharmaceutical brands were studied through
the evaluation of weight variation, hardness, friability, disintegration time, dissolution profile
and drug content.
3. METHODOLOGY
Various analytical methods and tests are important for the development and
manufacture of pharmaceutical formulations. The evaluation was done according to USP and
BP standards.
3.1 Identification Test of Paracetamol
Two identification tests were conducted in the compliance to the British
pharmacopeias.
3.2 Weight Variation
Tablets of each brand were weighed individually using a digital analytical balance
Shimadzu. The percentage deviation of the individual tablets from the mean was determined
according to USP.
3.3 Hardness Test
A tablet was placed vertically on the Monsanto Hardness tester. The load was then
applied along the radial axis of the tablet. The weight or load required for breaking the tablet
was noted down. Similarly it was done for 10 tablets.
3.4 Friability
It was performed using Roche Friabilator, 10 tablets were weighed and placed in
apparatus. The apparatus was rotated at a speed of 25 rpm. The apparatus was made to rotate
for 4 min. The tablets were then weighed and the weights were compared with the initial
weights. The % friability was calculated using the formula.
% F = [1 - (W/Wo)] x 100 Where, % F = Friability in %, Wo = Initial weight of tablets, W =
Weight of the tablets after revolution.
3.5 Tablet Disintegration
It was performed using Electro Lab disintegration apparatus, 6 tablets were placed in
disintegration test apparatus. It was maintained at 37 ± 0.2oC containing simulated gastric
fluid (0.1N HCl). Noted down the time taken for tablets to disintegrate.
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International Journal of Pharmaceutical Science and Health Care
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Issue 4, Vol. 4. July-August 2014
ISSN 2249 – 5738
3.6 Dissolution Test
For this test USP Type-1 (Basket) 6 Paddle Apparatus was used. The tablets formed
were immersed into 900 ml. of dissolution medium, simulated gastric fluid (0.1N HCl). The
temperature of the dissolution medium was maintained at 37 ± 0.2oC. The basket was rotated
at a speed of 150 rpm. After an interval of every 10 minutes, 2 ml. of the medium was pipette
out and replaced with fresh medium (0.1N HCl). This was continued all along for one hour.
The pipetted out samples were then diluted to 10 ml. with fresh dissolution medium and were
then filtered. The absorbances of the filtered samples were determined using U.V.
Spectroscopy at λ max 222 nm. According to USP [10] specifications not less than 80% (Q) of
the labeled amount of acetaminophen is dissolved within 30 minutes.
3.7 Assay
The assay was done to find out any difference between the actual amount of active
ingredient and the labeled amount.
10 tablets from each brand weighed and finely powdered then an accurately weighed portion
of powder equivalent to 150mg paracetamol were transferred to a 200ml volumetric flask , 50
ml of 0.1M sodium hydroxide and 100ml of distilled water was added and sonicated for15
minutes, then diluted to the volume and filtered.10ml of the filtrate was transferred
to100mlvolumetric flask and further diluted to 100ml with distilled water. Then 10ml of the
filtered solution with 10ml 0.1M NaOH was transferred to another 100ml volumetric flask
and the volume was completed with distilled water. The UV spectrophotometer was put at
zero by running a baseline (200-400nm) using 0.1 M NaOH solution as blank The
absorbances of the assay preparation was determined against the E1% at λ max 257nm with
Double beam UV Spectrophotometer using 0.1 M NaOH solution as a blank. The same
procedure was repeated for the standard using 150mg of powdered standard and the
absorbance determined, which was used to calculate the percentage content and content in mg
of paracetamol from each brand.
The concentration of each sample was also deterrnined using Beer Lambert’s law according
to BP. [11]
4. RESULTS AND DISCUSSION
The results of the present study conducted on six different brands of paracetamol
tablets, met the USP and BP requirements of quality control tests within specified limits.
4.1 Weight Variation
According to official books, the specified limit on weight variation for tablets more
than 324 mg is ± 5 %. It was found that all the tablets passed the USP specifications for
weight variation as none of the brands deviated by upto ±5% from the mean value. Weight
variation gives a rough idea of content uniformity, but not a confirmatory test.
4.2 Friability
Friability is another important parameter that is related to hardness, disintegration and
dissolution. According to the USP. [12] the allowed limit of friability is not more than 1.0 % of
weight Loss. The friability was carried out for all the brands. It was less than 1% for all the
brands except F tablets that were more fragile (2.0%), which may be due to the nature of the
binders and additives used in the manufacturing procedures.
4.3 Hardness
In the pharmaceutical industry, hardness of the tablets is an important parameter
because pharmaceutical tablets must have sufficient ability to survive the handling forces
during packaging and shipping. However, if the hardness exceeds a certain limit, it increases
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International Journal of Pharmaceutical Science and Health Care
Available online on http://www.rspublication.com/ijphc/index.html
Issue 4, Vol. 4. July-August 2014
ISSN 2249 – 5738
the disintegration time, which ultimately affects the bioavailability. [13] Hardness is not an
official test so there is no such a compendial limit for hardness but a crushing strength of
between 4 kg/cm2 to 10 kg/cm2 is considered minimum requirement for a satisfactory tablets.
The average hardness of the local and multinational brands was within the limits.
4.4 Disintegration Time
Disintegration could be related to dissolution and similarly availability of drug to
body (absorption) and finally the therapeutic efficacy of product. The result showed that
disintegration time of all the selected tablets was found to be within specified limits of USP
and BP. According to BP [14] (Figure 2), which specifies 15 minutes as disintegration time
where as uncoated USP tablets have disintegration time standards as low as 5 minutes. Total
of the results of above evaluated physicochemical parameters were presented in (Table 2) .
4.5 Assay
Test for percentage of content is based on the assay of the individual content of active
ingredient of a number of single dose units. All the paracetamol tablets i.e., multinational and
local brands, contained the paracetamol with in 100 ±10 % of the labeled claim. The USP and
BP specifications for assay are that the paracetamol contents should not be less then 90 % and
not more then 110 (Table 3). Therefore, the assay results ascertain the presence and
compendial quality of the drug in all products (Figure 3).
4.6 Dissolution
Dissolution of the all the selected brands of paracetamol tablets was found to be
within the specified limits of not less than 80 % in 30 min (USP) and not less than 70% (BP).
Excellent results were obtained for all brands of tablets (Table 4). Depending upon the above
facts & cost effectiveness it can be clearly stated that the commercially available local brands
are of same quality and clinical effectiveness as the multinational brands available (Figure 4).
So, the trends about the local brands should be changed. Since the analgesic and antipyretic
medications containing paracetamol are used by patients to relief pain within short time to
give the onset of action which depends mainly on the release of the drug.[15].
Table 1: Manufacturing date and expiry date of various paracetamol brands under test
Multinational Manufacturing
Tablet Code date
Expiry date
A
B
C
D
Nov. 2016
Nov. 2016
March 2016
Feb. 2017
Dec. 2013
Dec. 2013
March 2013
March 2013
Local
Tablet
Code
E
F
Manufacturing
date
Expiry date
Sept. 2013
Nov. 2013
Aug. 2016
April 2015
Table 2: Comparative evaluation of different quality control parameters of paracetamol
tablets
Tablet Code
A
B
C
D
E
F
Weight
Variation %
0.6
0.9
0.65
0.7
1.0
1.2
Friability %
0.45
0.34
0.43
0.36
0.55
2.0
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Hardness
(kg/cm2 )
4.3
5.3
4.6
5.1
4.4
4.0
Disintegration
Time (Min.)
2
3.2
2.5
3
2.43
2.12
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Issue 4, Vol. 4. July-August 2014
ISSN 2249 – 5738
Table 3: Showing result obtained for percent content of paracetamol tablets by UV method
Tablet Code
Concentration
(mg/ml)
0.000731
0.000700
0.000696
0.000718
0.000685
0.000660
A
B
C
D
E
F
Absorbance
% Content
Content (mg)
0.523
0.501
0.498
0.514
0.490
0.472
102.23
97.0
97.34
100.41
95.80
92.32
511.15
485
486.7
502.05
479.05
461.6
Table 4: Comparative Evaluation of dissolution profile of paracetamol tablets
Time interval
( Minutes)
10
20
30
40
50
60
% Release of Paracetamol content
B
C
D
E
77
74
70
67
87
90
84
82
94
93
94
91
96.5
97
95
94.5
91
90
99
89
89
88.5
94
87
A
71
81
93
97
99.5
97
F
63
80
90
92
88
86
3.5
Time (Min.)
3
A
2.5
B
2
C
1.5
D
1
E
0.5
F
0
A
B
C
D
E
F
% Content
Fig 2: Disintegration time (Min.) of different brands of Tablets
104
102
100
98
96
94
92
90
88
86
A
B
C
D
E
F
A
B
C
D
E
F
Fig 3: Assay of different brands of Paracetamol tablets
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Issue 4, Vol. 4. July-August 2014
ISSN 2249 – 5738
% Drug Release
Comparative Dissolution Profiles of all Paracetamol Brands
120
100
80
60
40
20
0
A
B
C
D
E
0
10
20
30
40
50
60
F
Time (Min.)
Fig 4 : Dissolution profile of different brands of Paracetamol tablets
CONCLUSION
The in-vitro physical and chemical evaluation of selected commercial brands i.e.,
Multinational & Local brands of paracetamol available in Maharashtra state proved the
quality and efficacy according to the standards of USP and BP requirements. As quality
control parameters are related to one another from initial step to pharmacological action of
the drug, a high-quality tablet should meet all the standard quality parameter for getting its
desired therapeutic response. Quantitative variation often exists among drugs of different
product. However, despite the variation most drug products are within the official limit. It
reflects that these formulations will be definitely producing desired effects as analgesic &
anti pyretic in patients. So the prescribing patterns should be changed depending upon the
socio-economic status of patients. In conclusion, all the brands tested in this study were
physically and chemically equivalent and it is preferred to be stored at 25ºC.
ACKNOWLEDGEMENT
The authors are grateful to GSK Pharmaceuticals for their kindly donation of
paracetamol working standard.
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