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Comparative evaluation of quality control parameters of some etoricoxib generic

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 The Pharma Innovation Journal 2017; 6(5): 29-33

ISSN (E): 2277- 7695

ISSN (P): 2349-8242
NAAS Rating 2017: 5.03 Comparative evaluation of quality control parameters
TPI 2017; 6(5): 29-33
© 2017 TPI of some etoricoxib generic tablets available in
www.thepharmajournal.com
Received: 15-03-2017 Bangladesh
Accepted: 16-04-2017

Amit Kumar Roy Amit Kumar Roy, Md Mamun Ahmed, Md Mahedi Hasan Nahid, Kaniz
Pharmaceutical Technology
Research Laboratory, Afroz Tanni and Mohammad Shahriar
Department of Pharmacy,
University of Asia Pacific, Abstract
Dhaka, Bangladesh
Etoricoxib is a highly selective cyclooxygenage-2 (COX-2) inhibitor administered orally as an analgesic
drug that has shown some improved efficacy versus traditional NSAIDs. The study was intended to
Md Mamun Ahmed
Pharmaceutical Technology evaluate different physicochemical parameters of generic etoricoxib tablet from different manufacturers
Research Laboratory, using in vitro tests. The tested brand products had satisfactory hardness, average weight, friability,
Department of Pharmacy, disintegration and potency. All the brands released more than 80% drug in the first 45 minutes except for
University of Asia Pacific, brand E9. The dissolution profiles were compared with the use of difference factor (f1) and similarity
Dhaka, Bangladesh factor (f2), showing that all the brands except E9 are similar with brand E1 and can be used
interchangeably.
Md Mahedi Hasan Nahid
Pharmaceutical Technology Keywords: Etoricoxib, In vitro equivalence, Dissolution, Difference factor (f1), Similarity factor (f2).
Research Laboratory,
Department of Pharmacy,
University of Asia Pacific,
1. Introduction
Dhaka, Bangladesh The oral route of drug administration is the most important method of administering drugs for
systemic effects. Tablets represent unit dosage forms in which one usual dose of the drug has
Kaniz Afroz Tanni been accurately placed. The main purpose of designing and manufacturing of the compressed
Lecturer, Department of tablet is to deliver orally the correct amount of drug in the proper form, at or over the proper
Pharmacy, University of Asia
Pacific, Dhaka, Bangladesh
time and in the desired location, and to have its chemical integrity protected to that point.
Manufacturing methods and the excipients used in the production process could affect the
Mohammad Shahriar quality and release profile of medicament. Therefore, to ensure the necessary quality, drug
Pharmaceutical Technology manufacturers are required to examine their products during and after manufacturing at various
Research Laboratory, time intervals. So, the selection of one product from several generic drug products of the same
Department of Pharmacy,
University of Asia Pacific,
active ingredients is very important for healthcare workers [1].
Dhaka, Bangladesh The non-steroidal anti-inflammatory drugs (NSAIDs) are widely used long term for the
treatment of rheumatoid and osteoarthritis to relieve the pain and inflammation [2]. The
intermediate iso enzymes responsible for prostaglandin biosynthesis, cyclo-oxygenase (COX)
1 and 2, have been the target of arthritis therapy using non-steroidal anti-inflammatory drugs
[3]
. NSAIDs are associated with a number of adverse effects. These include alterations in renal
function, effects on blood pressure, hepatic injury and platelet inhibition which may result in
increased bleeding [4]. COX-2 has been shown to be primarily responsible for the synthesis of
prostanoid mediators of pain, inflammation and fever. Selective inhibition of COX-2 by
etoricoxib decreases these clinical signs and symptoms of pain with decreased potential for GI
toxicity and effects on platelet aggregation [5].
Etoricoxib, [5-chloro-2-(6-methylpyridin-3-yl)-3-(4-methylsulfonylphenyl) pyridine], is an
orally active agent that selectively inhibits COX-2. It is a widely prescribed anti-inflammatory
drug available in tablet strengths of 30, 60, 90, and 120 mg. It is a poorly soluble and highly
permeable BCS class 2 drug [6]. Its aqueous solubility is low and highly pH-dependent.
Pharmacokinetic studies, however, show that when administered orally, etoricoxib is
completely and rapidly absorbed, with an oral bioavailability of up to 100% [7]. It is used in the
treatment of rheumatoid arthritis, osteoarthritis, post-operative dental pain, chronic musculo-
skeletal back pain, primary dysmenorrhoea and acute gout. Moreover, recent studies evidenced
Correspondence its efficacy in patients with ankylosing spondylitis. But it’s very low aqueous solubility and
Kaniz Afroz Tanni
Lecturer, Department of
poor dissolution can cause formulation problems and limit its therapeutic application by
Pharmacy, University of Asia delaying the rate of absorption and the onset of action [8]. Etoricoxib is available in 55
Pacific, Dhaka, Bangladesh countries in Europe, Latin America and the
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The Pharma Innovation Journal
 
Asia-Pacific region and is under development in the US. pharmaceutical company in Bangladesh. Etoricoxib tablets
There have been an estimated 2.4 million patient-years of (60 mg) of nine different brands were purchased from
exposure with etoricoxib 60, 90, and 120 mg outside the registered pharmacy stores of Dhaka, Bangladesh. The
United States since 2001. samples were properly checked for their physical appearance,
The purpose of the study is to make a comparison of product name of manufacturer, batch number, manufacturing date,
quality control parameters, differentiate visual uniqueness and expiry date, manufacturing license number, DAR number and
identify differences in physicochemical properties between maximum retail price. For ethical concerns, the tablets were
different marketed etoricoxib tablets in Bangladesh. randomly coded as E1, E2, E3, E4, E5, E6, E7, E8 and E9 so
that the identity of the manufacturer can be blinded. The label
2. Materials and Methods information of nine different brands of etoricoxib tablets are
2.1 Collection of Sample Products shown in (Table 1).
Standard of etoricoxib was a kind gift from a reputed

Table 1: Label information of nine different brands of etoricoxib tablets

Brand code Mfg. date Exp. date Pack size found Price of pack found (BDT) Price / 10 units (BDT)
E1 April 2016 April 2018 100 500 50
E2 May 2016 May 2018 100 550 55
E3 June 2016 June 2018 100 550 55
E4 June 2016 June 2018 100 600 60
E5 June 2016 June 2018 100 600 60
E6 October 2016 October 2018 100 650 65
E7 July 2016 July 2018 100 600 60
E8 March 2016 March 2018 100 600 60
E9 April 2016 April 2018 100 600 60

2.6 Standard assay preparation

The powder equivalent to 100 mg of etoricoxib was taken and
dissolved in 0.1 N HCl (pH 1.2). Then it was diluted to
produce a final concentration of 0.010 mg/ml (10 μg/ml) for
working solution. Then this solution was again serially diluted
to get concentrations of 1 μg/ml, 2 μg/ml, 3 μg/ml, 4 μg/ml, 5
μg/ml, 6 μg/ml, 7 μg/ml, 8 μg/ml, 9 μg/ml and 10 μg/ml
respectively. Absorbance values were then measured at the
maximum wavelength (λ max) of etoricoxib using a UV-VIS
spectrophotometer (UV-1700, Shimadzu, Japan). Maximum
wavelength (λ max) was obtained by scanning samples at
different wavelength ranging from 200 to 400 nm and it was
found to be 234 nm.

Fig 1: Price fluctuation among different brands of etoricoxib 2.7 Disintegration test
available in local market of Bangladesh Disintegration test is a measure of the time required under a
given set of conditions for a group of tablets to disintegrate
2.2 Diameter and thickness inspection into particles which will pass through a 10 mesh screen. It has
Twenty tablets from each brand were selected for diameter to be pointed out that a product which fails disintegration will
and thickness test. Diameter and thickness were determined presumably fail dissolution criteria [9]. Six tablets from each
by using digital slide caliper. Mean thickness, diameter and brand were employed for the test in distilled water at 37 °C
their standard deviations (SD) were calculated. using a tablet disintegration tester ED-20 (Electrolab,
Mumbai, India) as per condition described by United State
2.3 Hardness test Pharmacopeia, 2014 [10]. The disintegration time (DT) was
Crushing strength (N) was determined with an automatic noted down and by definition, it’s the time taken for the entire
hardness tester (VEEGO, INDIA). Twenty tablets were tablet to disintegrate completely.
randomly selected from each brand and the pressure required
to crush each were recorded. 2.8 Measurement of potency
Analysis of drug potency in tablets is to evaluate the tablets
2.4 Friability test potential for efficacy by monitoring the presence of drug in
Twenty tablets from each brand were weighed and subjected dosage form and also requisite for the establishment of
to rotation by employing a VEEGO friabilator (VFT-2, India) stability data. Sample was prepared by weighing and crushing
which was operated at 25 RPM for 4 minutes. All tablets were 10 tablets, transferring amount of drug powder equivalent to
weighed before and after 100 revolutions. 10 mg in 0.1 N HCl (pH 1.2) solution and placing it in
sonicator. The portion of solution was filtered and the filtrate
2.5 Weight variation was suitably diluted to give concentrations of 1 μg/ml, 2
For weight variation twenty tablets from each brand were μg/ml, 3 μg/ml, 4 μg/ml, 5 μg/ml, 6 μg/ml, 7 μg/ml, 8 μg/ml,
weighed individually using an analytical balance (TE214S, 9 μg/ml and 10 μg/ml respectively. Absorbance was taken at
Sartorious Germany). 234 nm by using UV-visible spectrophotometer. Finally the

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potency of different tablets was determined by using the on attrition [13]. Tablet hardness was found between 76-183 N.
following equation: A force of about 40 N is the minimum requirement for a
satisfactory tablet [14]. So, the tablets of all the brands

% Potency = x 100 complied with this requirement were considered as of good

quality.
2.9 Dissolution Test
The dissolution test was undertaken for six randomly selected 3.4 Friability test
tablets using dissolution apparatus paddle (Electrolab, India). It is the tendency of tablets to powder, chip, or fragment and
The dissolution medium was 900 ml of 0.1 N HCl (pH 1.2) this can affect the elegance appearance, consumer acceptance
which was maintained at 37±0.5 °C. Rotations were 50 of the tablet and also add to tablet’s weight variation or
revolutions per minute. 10 ml of sample was withdrawn after content uniformity problems [15]. Tablet hardness is not an
5 and 15 minutes and then after every 15 minutes. Standard absolute indicator of strength and therefore another measure
solution was prepared accordingly. Absorbance was measured of a tablet’s strength, its friability, is often measured which is
at 234 nm. To determine the concentration of samples, help designed to evaluate the ability of the tablet to withstand
from the standard curve of pure API was taken. Using the Y= abrasion in packaging, handling and shipping which can lead
mX + C equation, sample concentration was calculated. to capping, chipping, abrasion or even breakage of the tablets.
Friability test is now included in the United States
3. Results and discussion Pharmacopeia as a compendial test [16]. The compendial
3.1 Price fluctuation specification for friability is 1%. Usually harder the tablets
Price, manufacturing and expiry date of etoricoxib tablets less will be the percentage friability and vice versa [17]. It was
were observed in the drug outlets on single visit during found that nine different brands of etoricoxib tablets were in
medicine collections. The highest price was for brand E6 (6.5 accordance with the stated USP guideline (Table 2).
taka per tablet) and minimum for brand E1 (5 taka per tablet)
while there was no major variation in the physical appearance 3.5 Test of uniformity of weight
of the tablets (Figure 1). The weight variation test would be a satisfactory method of
determining the drug content uniformity of tablets if the
3.2 Diameter and thickness test tablets were all or essentially all (90 to 95%) active
As the weight of a compressed tablet is dependent on density, ingredient, or if the uniformity of the drug distribution in the
diameter, and thickness, determination of the diameter and granulation or powder form from which the tablets were made
thickness of the tablets at regular intervals during the were perfect [15]. The average weight of tablets of each brands
production may prevent potential problems related to tablet were between 130 mg-324 mg and USP specification for
weight and content uniformity at an early stage [11]. Among weight variation of tablets is ±7.5% for this average weight
six brands, brand E4 had the highest average diameter (13.38 range. From the results, it can be said depending upon the
mm) whereas brand E8 had the lowest average diameter (6.48 USP specification that, the % deviations of all the brands of
mm). The average thickness was found to be between the etoricoxib 60 mg tablets are within range ±7.5% deviation.
ranges of 3.10 mm-5.25 mm (Table 2). So, all brands comply with USP specification.

3.3 Hardness test 3.6 Disintegration test

Hardness is referred to as non-compendial test. The hardness Disintegration time depends on the product, the stirring speed
of the tablet depends on the materials used, amount of binder, etc [15]. Disintegration time affects release of drug content
space between the upper and lower punches at the time of from its dosage form. It has to be pointed out that a product
compression and pressure applied during the process of which fails disintegration will presumably fail dissolution
compression [12]. The testing of tablet hardness and friability criteria because the disintegration tests do serve as a
plays a pivotal role in both product development and component in the overall quality control of tablets
subsequent quality control because high hardness values may manufacturing [9]. According to BP specification, film coated
result in increased disintegration time and decreased tablets should disintegrate within 30 min, while the USP
dissolution time. As opposed to this situation, high friability specifies that both uncoated and film coated tablets should
values may be observed in case of low hardness values. disintegrate within 30 min. Here all brands of etoricoxib
Measuring the hardness of a tablet is not a reliable indicator tablets were film coated and maximum time for disintegration
for tablet strength as some formulations when compressed was found 7.06 min in case of brand E3 (Table 2)
into very hard tablets tend to cap or lose their crown portions

Table 2: A summary of the quality control tests undertaken on different brands of etoricoxib tablets
Brands Diameter (mm) Thickness (mm) Friability (%) Hardness (N) Weight Variation (gm) DT (min) Potency (%)
E1 8.07±0.01 3.10±0.02 0.25 84.67±0.83 164.64±1.49 2.17±0.52 98.03
E2 8.28±0.02 3.40±0.02 0.14 61±0.87 190.29±1.53 2.82±0.55 95.79
E3 10.44±0.01 3.84±0.02 0.23 53±0.91 180.57±1.66 7.06±0.52 91.68
E4 13.38±0.01 5.25±0.03 0.03 126±0.73 368±1.88 1.88±0.59 99.56
E5 10.08±0.03 3.15±0.06 0.04 183±0.80 123±1.33 2.47±0.57 95.77
E6 7.13±0.03 3.72±0.04 0.09 96.66±0.80 153±1.75 1.54±0.52 90.75
E7 9.20±0.03 3.32±0.03 0.19 76±0.83 147.05±1.22 2.2±0.66 97.59
E8 6.48±0.01 3.46±0.03 0.11 89.33±0.97 121.3±2.12 1.57±0.69 100.93
E9 10.56±0.01 4.34±0.03 0.1 130.67±0.87 260.1±1.06 3.3±0.88 90.52
*Values are expressed as mean± SD

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The Pharma Innovation Journal  
 
3.7 Potency test brands indicated increase in drug release after every 15
Potency of all the brands was found within 90.52-100.93%. minutes although this increase varied from brand to brand.
Etoricoxib is an INN drug; no official specification for the After 60 minutes interval, brand E4 showed maximum drug
drug’s potency is available yet. For highly potent, low-dose release (98.8%) and brand E9 exhibited minimum drug
drugs this range is usually not less than 90% and not more release (72.1%). Since all the brands released more than 80%
than 110% of the labeled amount. Since the present study was drug in the first 45 minutes except for brand E9, it can be
conducted with large dose etoricoxib tablets (60 mg), percent assumed that all the brands possessed good dissolution profile
potency should be within 95%-105% [10]. All the brands met although the brands were manufactured by different
this specification (Table 2). companies using different excipients in different ratio (Table
3)
3.8 Dissolution test
Intra-brand comparison of the drug release profile of all the

Table 3: Dissolution profile of nine brands of etoricoxib tablets

Time % Drug Release
(min) E1 E2 E3 E4 E5 E6 E7 E8 E9
0 0 0 0 0 0 0 0 0 0
5 24.4±0.66 25.6±0.88 22.5±0.53 28.1±0.72 28.9±0.83 22.9±0.78 39.3±0.75 39.6±0.86 32.6±0.61
15 44.3±0.53 42±0.86 43.7±0.56 45.3±0.78 44.8±0.88 44.1±0.75 46.9±0.79 53±0.86 40±0.69
30 84.6±0.61 84.4±0.86 80.5±0.58 85.5±0.75 84.1±0.82 76.8±0.71 68.4±0.79 74±0.80 55.6±0.63
45 92.7±0.66 93.3±0.86 89±0.59 95.3±0.72 92.6±0.88 87.2±0.78 89±0.75 92.5±0.86 61.6±0.63
60 97.4±0.68 98.6±0.82 94.2±0.52 98.8±0.79 95.6±0.88 90.1±0.75 98.4±0.73 96.8±0.89 72.1±0.61
*Values are expressed as mean± SD

3.9 Comparison of dissolution data between 50 and 100. So, all the brands except brand E9 can
Difference factor (f1) and similarity factor (f2) were be used interchangeably with brand E1.
calculated to compare the dissolution profile. The following
equations were used to calculate f1 and f2. Where n is the 4. Conclusion
number of time points, Rt is the dissolution value of reference Quality of product refers to its confining to the standards pre-
product at time t and Tt is the dissolution value for the test set to assure the desired purpose. A quality product gives not
product at time t. Similarity factor (f2) has been adopted by only better therapeutic efficacy but also gives consumer
FDA and the European Agency for the Evaluation of satisfaction and increases its market demand. So, a
Medicinal Products by the Committee for Proprietary pharmaceutical industry follows the international standards to
Medicinal Products (CPMP) to compare dissolution profile. ensure quality product and to give proper safety and efficacy.
According to the FDA guidance, dissolution profiles are In the current industrial practice, to compare with the multi
similar if f1 values are between 0 and 15 and f2 values are brand generic molecules and to provide enough therapeutic
between 50 and 100. Table 4 shows the f1, f2 values of activity of the dosage form, in-vitro tests play a significant
different brands in respect of brand E1 as a reference brand role. Drug release and potency were satisfactory for all
[18]
brands. As a result, patients can safely switch from one brand
to another

5. References
1. Chow SC. Pharmaceutical validation and process controls
in drug development. Drug Information Journal. 1997;
31(1):1195-1201.
2. Galati G, Tafazoli S, Sabzevari O, Chan TS, O'Brien PJ.
Idiosyncratic NSAID drug induced oxidative stress.
Chemico-Biological Interactions. 2002; 142(1):25-41.
3. Shavi GV, Nayak UY, Raghavendra R, Shrawan B,
Reddy MS. Enhanced dissolution and bioavailability of
Etoricoxib in solid dispersion systems: An investigation
Table 4: f1 and f2 of nine brands of etoricoxib tablets tested
into the role of carrier matrix on stability, in vitro and in
Pair Difference Similarity vivo performance. Journal of Pharmacy and
Comparison Factor (f1) Factor (f2) Pharmaceutical Sciences. 2016; 5(1):55-63.
E2 vs E1 1.65 73.85 4. Ong CKS, Lirk P, Tan CH, Seymour RA. An evidence-
E3 vs E1 3.95 58.2 based update on non-steroidal anti-inflammatory drugs.
E4 vs E1 2.8 82.35 Clinical Medicine and Research Journal. 2006; 5(1):19-
E5 vs E1 2.12 82.5 34.
E6 vs E1 6.46 65 5. Sowjanya JN, Neetha M, Sirisha G, Aruna K. Design and
E7 vs E1 11.12 52
evaluation of Etoricoxib fast dissolving tablets.
E8 vs E1 10.27 53.5
International Journal of Medicine and Nanotechnology.
E9 vs E1 28.49 35
2015; 2(4):249-257.
6. Okumu A, Dimaso M, Lobenberg R. Computer
It can be seen from the Table 4 that, all the brands except E9
simulations using GastroPlus to justify a biowaiver for
has difference factor between 0 and 15, and similarity factor
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The Pharma Innovation Journal  
 
etoricoxib solid oral drug products. European Journal of
Pharmaceutics and Biopharmaceutics. 2008; 72(1):91-98.
7. Agrawal NG, Porras AG, Matthews CZ, Rose MJ, Woolf
EJ, Musser BJ et al. Single and multiple dose
pharmacokinetics of etoricoxib, a selective inhibitor of
cyclooxygenase-2 in man. The Journal of Clinical
Pharmacology. 2003; 43(3):268-76.
8. Das A, Nayak AK, Mohanty B, Panda S. Solubility and
dissolution enhancement of etoricoxib by solid dispersion
technique using sugar carriers. ISRN Pharmaceutics
2011, 1-8.
9. Du J, Hoag SW. Characterization of excipient and
tableting factors that influence folic acid dissolution,
friability, and breaking strength of oil- and watersoluble
multivitamin with mineral tablets. Drug Development
and Industrial Pharmacy. 2003; 29:1134-1147.
10. United State Pharmacopoeia. United States
Pharmacopoeial Convention. Rockville, Maryland, 2014.
11. Akgeyik E, Kaynak MS, Çelebier M, Altınöz S, Şahin S.
Evaluation of pharmaceutical quality of conventional
dosage forms containing paracetamol and caffeine
available in the Turkish drug market. Dissolution
Technology. 2016; 23(2):36-41.
12. Banker GS, Anderson NR. The Theory and Practice of
Industrial Pharmacy. Varghese Publishing house,
Philadelphia, 2011, 293-345.
13. Pisek R, Korselj V, Vrecer F. Comparison of direct rotor
pelletization (fluid bed) and hign shear pelletization
method for pellet production. Pharm and Biopharm.
2002; 53:327-333.
14. Allen LV, Popovich NG, Ansel HC. Ansel's
pharmaceutical dosage forms and drug delivery systems.
8th, Lippincott Williams & Wilkins, Philadelphia, 2011,
225-256.
15. Lachman L, Lieberman H, Kanig J. The theory and
practice of industrial pharmacy. 3rd, Varghese
publication house, Delhi, 1987, 293-345.
16. US Pharmacopeia National Formulary USP 23/NF 18.
United States Pharmacopeial Convention. Inc., Rockville,
MD, 1995.
17. Oishi TS, Nimmi I, Islam SMA. Comparative in vitro
Bioequivalence Analysis of Some Generic Tablets of
Atorvastatin, a BCS Class II Compound. Bangladesh
Pharmaceutical Journal. 2011; 14(1):61-66.
18. Waiver of in vivo bioavailability and bioequivalence
studies for immediate-release solid oral dosage forms
based on a biopharmaceutics classification system;
guidance for industry; U.S. Department of Health and
Human Services, Food and Drug Administration, Center
for Drug Evaluation and Research (CDER), U.S.
Government Printing Office: Washington, DC, 2000.

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