Evaluation of In-Vitro Quality Control

Parameters of Etoricoxib 90 Mg Tablets

Marketed in Bangladesh

A project report submitted to the Department of Pharmacy, University of Asia Pacific

in partial fulfillment of the requirements for the degree of
Bachelor of Pharmacy (Honors)

Submitted By
Registration No.: 18203005
Submission Semester: Spring 2022
Submission Date: 20 October 2022

Department of Pharmacy
University of Asia Pacific
 Abstract
Objective: Etoricoxib is an INN (International Nonproprietary Name) drug available in a
tablet dosage form that is used as a selective cox-2 inhibitor for the treatment of
rheumatoid arthritis and osteoarthritis. To identify excellent quality of etoricoxib and to
prevent sub-standard products, quality control testing of etoricoxib created by different
pharmaceuticals in Bangladesh should be conducted. This study intends to survey the
quality boundaries of Etoricoxib Tablets from a reputable pharmaceutical company in
Bangladesh and to evaluate if the brands follow the USP guidelines. Materials and
Methods: To assess the quality Coxia 90 mg tablets from ACI limited was chosen and
Weight variation, hardness, thickness and diameter, friability, disintegration time,
dissolution test and potency were tested for the tablets. To determine in-vitro dissolution,
the UV-Spectrophotometric method was applied. For every test, arithmetic mean and
standard deviation were calculated, and values were verified to see if they were within
the acceptable range. Results: In our study, we found that the average weight, diameter
and thickness of Coxia tablets were 186.75 mg, 8.05 mm and 3.29 mm respectively. The
average hardness and disintegration time were 8.20 Kp and 4.75 minutes respectively. %
Friability and potency were 0.23 and 97.97% respectively. Conclusion: All the tablets
of Coxia passed the weight variation, hardness, % friability, disintegration time, potency
and dissolution test according to USP guidelines. So, our study illustrates a good quality
of Coxia tablets with concerning potency results.

I
 Table of Contents

Si. No. Topic Page

1 Abstract I

2 Table Of Contents II

3 List Of Tables V

4 List Of Figures VI

Chapter 1-Introduction

Si. No. Topic Page

1 General Information 1

1.1 Drug Information 1

1.1.1 Drug profile 2

1.2 Chemistry 2

1.2.1 Synthesis of Etoricoxib: 3

1.3 Pharmacological Properties of Etoricoxib 3

1.3.1 Pharmacodynamics Properties of Etoricoxib 3

1.3.2 Clinical efficacy 4

1.3.3 Safety 5

1.3.4 Pharmacokinetic Properties 6

1.4 Interactions with other drugs 8

1.4.1 Indications 9

II
1.4.2 Dosage and Administration 9

1.5 Side Effects 10

1.5.1 Contraindications 10

1.5.2 Adverse Effect 11

1.6 Fertility, Pregnancy and Lactation 11

1.7 Quality Control Specifications 12

1.7.1 Weight Variation 12

1.7.2 Hardness Test 12

1.7.3 Disintegration Test 12

1.7.4 Dissolution Test 13

1.7.5 Friability Test 13

1.7.6 Potency Test 14

1.8 Purpose of the study 14

Chapter 2- Materials and Methods

Si. No. Topic Page

2 Study Outline 16

2.1 Sample Collection 16

2.2 Identification of Sample 16

2.3 Reagents Used in The Experiment 16

2.4 Equipment Used in The In-Vitro Studies 17

2.5 Analytical Method 18

III
2.5.1 Weight Variation Test 18

2.5.2 Measurement of Thickness and Diameter 19

2.5.3 Hardness Test 21

2.5.4 Friability Test 21

2.5.5 Disintegration Test 22

2.5.6 Dissolution Test 23

2.5.7 Preparation of Standard Curve of Etoricoxib 25

2.5.8 Potency Determination 26

Chapter 3- Results and Discussion

Si. No. Topic Page

3 Results and Discussion 29

3.1 Weight Variation Test 29

3.2 Determination of Diameter and Shape 31

3.3 Determination of Thickness 33

3.4 Determination of Hardness 35

3.5 Determination of Friability 36

3.6 Determination of Disintegration Time 37

3.7 Determination of Standard Curve 38

3.8 Determination of Potency 40

IV
3.9 Determination of Dissolution 41

List of Tables

Si. No Title Page

2.1 Label Information of Etoricoxib Tablets 16

2.2 Reagent Used in This Experiment 16

2.3 Equipment Used for Different In-vitro Tests 17

2.4 Weight Variation Specification 19

2.5 Specifications of Disintegration Test According to USP 23

2.6 Dissolution Study Parameter for Etoricoxib Tablet 25

3.1 Weight Variation of Etoricoxib tablets 29

3.2 The Average Weight, Maximum Weight and Minimum 30

Weight of Etoricoxib tablets

3.3 Average Diameter of Etoricoxib tablets 32

3.4 The Highest Diameter and Lowest Diameter of Etoricoxib 33

tablets

3.5 Average Thickness and % of Deviation of Etoricoxib tablets 34

3.6 The Maximum Thickness, Minimum Thickness and Highest 35

% of Thickness Deviation, and Lowest % of Thickness
Deviation of Etoricoxib tablets

3.7 Hardness (kp) of Etoricoxib tablets 36

3.8 Etoricoxib tablets Friability Test 36

V
3.9 Disintegration Time of Etoricoxib Tablets 37

3.10 Determination of Absorbance 38

3.11 Determination of Potency of Etoricoxib tablets 40

3.12 % of Drug Release of Etoricoxib tablets -Tablet 1 41

3.13 % of Drug Release of Etoricoxib tablets -Tablet 2 42

3.14 % of Drug Release of Etoricoxib tablets -Tablet 3 43

3.15 Percentage Drug Release Comparison of Three Tablets 42

List of Figures

Si. No. Title Page

1.1 Structure of Etoricoxib 2

1.2 Synthesis of Etoricoxib 3

2.1 Electronic Balance 18

2.2 Digital Slide Calipers 20

2.3 Hardness Tester 21

2.4 Friability Tester 22

2.5 Disintegration tester 23

2.6 Dissolution Tester 24

2.7 UV-Visible Spectrophotometer 26

3.1 Average Weight of Etoricoxib tablets 30

3.2 Maximum and Minimum % of Deviation of Etoricoxib 31

tablets

VI
3.3 The Average Diameter of Etoricoxib tablets 33

3.4 The Average Thickness of Etoricoxib tablets 35

3.5 Average Hardness (kp) of Etoricoxib tablets 36

3.6 Percentage of Friability of Etoricoxib tablets 37

3.7 Graphical Representation of Disintegration Time 38

3.8 Graphical Representation of Standard Curve 39

3.9 Potency of Etoricoxib tablets 40

3.10 Percentage Drug Release Comparison of Three Tablets 43

3.11 Average % of Drug Release of Etoricoxib tablets 43

VII
Chapter -1
Introduction
1. General Information

Nonsteroidal anti-inflammatory medicines (NSAIDs) are a family of pharmaceuticals that have

been authorized by the FDA for use as antipyretic, anti-inflammatory, and analgesic agents.
NSAIDs are beneficial for treating muscular pain, dysmenorrhea, arthritic diseases, pyrexia,
gout, migraines, and as opioid-sparing medicines in some acute trauma situations owing to
these effects. (Dawood, 2006) NSAIDs are categorized into two types: non-selective and COX-
2 selective. COX-2 inhibitors are a kind of nonsteroidal anti-inflammatory medication
(NSAID) that targets cyclooxygenase-2, or COX-2, an enzyme that causes inflammation and
discomfort. (Day & Graham, 2004) The cyclo-oxygenase-2 (COX-2) enzyme is inhibited by
etoricoxib, making it a selective COX-2 inhibitor. This enzyme helps the body make
prostaglandins, which are other substances. At the locations of damage or injury, some
prostaglandins are created, which lead to pain and inflammation. Less prostaglandins are made
when COX-2 enzymes are inhibited, which lessens inflammation and discomfort (Stewart and
Dajani, 2019).

1.1 Drug Information

Nonsteroidal anti-inflammatory medications (NSAIDs) are often used to treat pain,

inflammation, and fever in clinical practice. These medications' pharmacological effects result
from their ability to prevent the production of prostaglandins by blocking the cyclooxygenase
enzyme (COX). The two isoforms of COX are COX-1 and COX-2. The prostaglandins
produced by COX-1, which are necessary for numerous physiological processes including
protecting the stomach mucosa, preserving renal homeostasis, and platelet aggregation, are
constitutively expressed in healthy tissues. On the other hand, COX-2 is in charge of producing
prostaglandins, which are molecules that regulate reactions to disease processes including pain,
fever, and inflammation. A selective COX-2 inhibitor called etoricoxib is used to treat pain and
rheumatoid arthritis as well as osteoarthritis (Shohag, et al., 2011).

Etoricoxib is metabolized via cytochrome P-450-dependent oxidation in individuals with liver

disease, leading to a prolonged elimination. For chronic usage, the daily maximum dosage
ranges from 60 to 90 mg, while the amount for severe pain is 120 mg. Arachidonic acid is not
converted into prostaglandins by etoricoxib because it binds to and inhibits the enzyme
cyclooxygenase-2 (COX-2). Apoptosis may be induced by COX-2 inhibition, which may also
reduce tumor cell growth and angiogenesis. Etoricoxib is a 2,3'-bipyridine having substitutions
at positions 3, 5, and 6' for 4-(methylsulfonyl) phenyl, chlorine, and methyl, respectively. It

1
functions as both a nonsteroidal anti-inflammatory medication and a cyclooxygenase 2
inhibitor. It combines the properties of an organochlorine molecule, a sulfone, and a bipyridine
derivative (Maheu, 2021).

1.1.1 Drug profile

Generic Name: Etoricoxib

IUPAC name: 5-chloro-3-(4-methanesulfonylphenyl)-6′methyl-[2,3′]-bipyridinyl]

Molecular formula: C18H15ClN2O2S

Molecular weight: 358.842 Da (Shavi et al., 2016).

Physical form: crystalline polymorphs (Takemoto et al., 2008).

Appearance: Off-White Solid.

Approval: It was granted a medicinal use patent in 2002 after being patented in 1996. More
than 80 nations across the globe presently allow it, but the FDA has not done so in the United
States. Before etoricoxib was authorized, the Food and Drug Administration (FDA) asked for
further information about its safety and efficacy. release authorization

1.2 Chemistry

Etoricoxib is a novel bipyridine COX-2 selective inhibitor. In comparison to celecoxib and

valdecoxib, etoricoxib is a methyl sulfone that lacks the component sulfonamide which results
an increased hypersensitivity risk (Friesen et al., 1998).

Structure of Etoricoxib:

Figure 1.1: Structure of Etoricoxib

2
1.2.1 Synthesis of Etoricoxib:
Process for the preparation of etoricoxib involves bromination of 2-amino pyridine derivative
with bromine in acetic acid to provide the bromide of 2-amino pyridine derivative. Coupling
of this bromide derivative with 4-(methylthio)phenyl-boronic acid is done in presence of a
suitable base, which is then oxidized to give the corresponding sulphon. Then the amino group
of sulphon is converted to corresponding halide. A second palladium catalyzed coupling of
sulphon halide derivative with an appropriately substituted metal containing aromatic yields
etoricoxib (Tartaggia, et al., 2013).

Figure 1.2: Synthesis of Etoricoxib

1.3 Pharmacological Properties of Etoricoxib

1.3.1Pharmacodynamics Properties of Etoricoxib

Mechanism of Action

Etoricoxib acts by blocking the cyclo-oxygenase-2 (COX-2) enzyme. This enzyme assists in
the creation of other substances in the body known as prostaglandins. This enzyme helps to the
creation of other substances in the body known as prostaglandins. Prostaglandins, which are
secreted at locations of injury or damage, induce pain and inflammation. Because COX-2
enzymes are blocked, fewer prostaglandins are created, resulting in decreased pain and
inflammation. Etoricoxib's specific inhibition of COX-2 decreases pain and inflammation
while minimizing GI toxicity and having no impact on platelet function (Brooks and Kubler,
2006).

3
1.3.2 Clinical efficacy

Osteoarthritis

Etoricoxib has been demonstrated in clinical studies to treat OA more effectively than a placebo
and similarly to conventional NSAIDs. Patients with osteoarthritis who take etoricoxib 60 mg
once a day report less pain and a better understanding of the severity of their condition. Such
favorable outcomes are seen as early as day two of treatment and might extend for 52 weeks.
Studies utilizing etoricoxib 30 mg once day showed effectiveness superior to placebo
throughout a 12-week treatment period. After six weeks of treatment, etoricoxib 60 mg
substantially outperformed 30 mg for all three main outcomes in a dose range experiment.
There are no studies on the 30-mg dose for hand osteoarthritis (Curtis et al., 2005).

Rheumatoid Arthritis

The efficacy of etoricoxib is similar to, or greater than, that of typical NSAIDs in persons with
rheumatoid arthritis. In patients having rheumatoid arthritis, etoricoxib 60 mg as well as 90 mg
once each day each of these delivers help in inflammation, pain and mobility. According to
study that have evaluated the 60 mg as well as 90 mg dose of the pharmaceutical, these
favorable results are retained all through 12-week therapy durations. Throughout research
testing the 60 mg dosage especially in contrast to the 90 mg dose, etoricoxib 60 mg one day
and 90 mg one day both were pretty effective than placebo. The 90 mg dosage was preferred
to the 60 mg dose (Feng et al., 2018).

Gouty Arthritis

In individuals with acute gouty arthritis, 120 mg of etoricoxib once daily for eight days treated
moderate to severe joint pain and inflammation, which was equivalent to indomethacin 50 mg
three times per day. Pain relief may occur as soon as 4 hours after using the medicine (Feng et
al., 2018).

Ankylosing Spondylitis

Etoricoxib has been demonstrated to be beneficial in a variety of painful disorders, including

primary dysmenorrhea, ankylosing spondylitis (AS), and acute postoperative pain. Etoricoxib
90 mg once day improves spine pain, inflammation, stiffness, and function in those with
ankylosing spondylitis. The therapeutic benefit of etoricoxib became obvious on the second
day of medication, and it lasted for the whole 52-week treatment term. A second trial
comparing etoricoxib dosages of 60 mg and 90 mg found that both doses were similarly helpful

4
when compared to naproxen 1,000 mg per day. After getting 60 mg every day for six weeks
and finding no impact, the dosage was adjusted to 90 mg once a day for six weeks (Curtis et
al., 2005).

Postoperative Oral Pain

In a clinical investigation on postoperative oral pain, etoricoxib 90 mg was administered once

daily for up to three days. In the subgroup of persons with moderate pain at beginning,
etoricoxib 90 mg exhibited equal analgesic efficacy to ibuprofen 600 mg and greater than
paracetamol/codeine 600 mg/60 mg and placebo (Clarke et al., 2014).

1.3.3 Safety

Cardiovascular

Selective and nonselective COX-2 inhibitors both possess the possibility of causing
cardiovascular toxicity. Clinical studies suggest that the selective COX-2 inhibitor class of
drugs may increase the risk of thrombotic events including myocardial infarction (MI) and
stroke when compared to placebo and other NSAIDs. Since etoricoxib's cardiovascular side
effects might become more severe with dose and length of exposure, the shortest duration and
lowest effective daily dosage should be utilized. Sometimes a patient's response to therapy and
the need for symptom relief should be reevaluated, especially in individuals with osteoarthritis
(Dong et al., 2018).

Renal

Renal prostaglandins could operate as a compensatory mechanism to keep the kidneys

perfusing. Therefore, etoricoxib use may reduce prostaglandin production and, therefore, renal
blood flow, which might impact renal function in the presence of diminished renal perfusion.
The most susceptible individuals to this reaction are those who have cirrhosis, uncompensated
heart failure, or markedly reduced renal function (Curtis et al., 2004).

Gastrointestinal

Upper gastrointestinal issues PUBs—perforations, ulcers, or bleedings—have happened to

etoricoxib users, some of which have been deadly. When administering NSAIDs to individuals
who are most susceptible to experiencing gastrointestinal issues, such as the elderly, those who
are already taking acetylsalicylic acid or another NSAID, or those who have a history of
gastrointestinal conditions including ulceration and GI bleeding. An increased risk of
gastrointestinal side effects such stomach ulcers or other gastrointestinal issues exists. even at

5
modest doses, etoricoxib combined with acetylsalicylic acid may cause side effects. Long-term
clinical studies have not shown a substantial difference in GI safety between NSAIDs +
acetylsalicylic acid and selective COX-2 inhibitors (Feng et al., 2018).

1.3.4 Pharmacokinetic Properties

Absorption

Orally taken etoricoxib absorbs effectively. The absorption of etoricoxib when administered
orally in single doses of 5, 10, 20, 40, and 120 mg has been shown to be linear throughout a
dosage range of around (5-120 mg) and is unaffected by formulation. Without regard to dosage
or formulation, the average peak plasma concentration (Cmax) for the dose range of 5–120 mg
is around 2186–95 ng/mL, and the average area under the plasma concentration–time curve
(AUC) from 0 to infinity (AUC) is roughly 0.31–0.34 g/h/L. Across the same dosage range, it
takes an hour to attain the Cmax (tmax). Etoricoxib absorption was unaffected by a high-fat
meal when taken at doses of 120 mg. The effect of altering the rate of absorption is a 2 hour
increase in Tmax and a 36% decrease in Cmax (Takemoto et al., 2008).

Distribution

Significant levels of etoricoxib are protein-bound, principally to plasma albumin. Etoricoxib

has a 92% binding rate to human plasma protein at dosages ranging from 0.05 to 5 mcg/mL. In
humans, the volume of distribution at steady state (Vdss) is close to 120 L. With larger oral
dosages, etoricoxib's area under the plasma concentration-time curve (AUC) rises (Takemoto
et al., 2008).

Metabolism

The cytochrome P450 (CYP) 3A4 enzyme is for the majority of etoricoxib metabolism (40-
90%); although, other CYPs including such CYP2D6, CYP2C9, CYP1A2, and CYP2C19 may
perform more or less equal roles in the activity balance. Despite the fact that CYP enzymes are
involved in etoricoxib metabolism, etoricoxib appears to have mild inhibitory effects on
CYP3A4, suggesting a low risk of drug-drug interactions. In vitro investigations demonstrate
that daily etoricoxib administration has little impact on CYP3A activity and is unlikely to affect
the metabolism of other drugs through a hepatic CYP3A dependent mechanism. The primary
metabolite of etoricoxib is a 6'carboxylic acid derivative generated by further oxidation of the
6'-hydroxymethyl derivative. These main metabolites are either ineffective COX-2 inhibitors
or very mildly active. These metabolites do not inhibit COX-1 (Takemoto et al., 2008).

6
Elimination

The primary route of elimination for etoricoxib metabolites is renal excretion. As the
unmodified medicine, less than 1% of the dose is removed through urine. After a once-daily
dosage of 120 mg, steady-state etoricoxib concentrations are reached in seven days, with an
accumulation ratio of about 2, corresponding to a half-life of around 22 hours. A 25-mg
intravenous dose is expected to result in plasma clearance of roughly 50 ml/min (Takemoto et
al., 2008).

Gender and Ethnicity

The distribution of etoricoxib seems to be similar in men and women, with no discernible
gender-related pharmacokinetic variations observed. Etoricoxib did not show any clinically
meaningful differences between patients of various ethnic backgrounds (Takemoto et al.,
2008).

Hepatic Impairment

When given etoricoxib 60 mg once day, individuals with mild hepatic impairment had a 16%
higher mean AUC than healthy patients receiving the same dosage. When administered
etoricoxib 60 mg every other day, patients with severe hepatic impairment exhibited mean
AUCs that were on par with those of healthy individuals receiving etoricoxib 60 mg once daily
(Agrawal et al., 2003).

Renal Impairment

Patients with moderate to severe renal insufficiency and those with end-stage renal disease
receiving hemodialysis have pharmacokinetic responses to a single dose of etoricoxib 120 mg
that are similar to those of healthy individuals. Dialysis clearance is around 50 ml/min;
hemodialysis contributes very little to elimination (Curtis et al., 2004).

7
1.4 Interactions with other drugs

Etoricoxib does not substantially raise or decrease CYP3A4 in vitro, hence it is unlikely to
have an impact on the pharmacokinetics of other medications that use CYP3A4. On the other
side, etoricoxib may have an impact on the plasma pharmacokinetics of digoxin, methotrexate,
oral contraceptives, and oral anticoagulants (Tacconelli et al., 2004).

Oral contraceptives

When etoricoxib 120 mg and an oral contraceptive pill containing 35-g of ethinylestradiol and
0.5-1 mg of norethindrone are administered concurrently for 21 days, the steady-state AUC(0-
24) h of ethinylestradiol increases by 50–60%, but norethindrone concentrations generally do
not increase in a clinically significant way (Tacconelli et al., 2004).

Warfarin

A rise of 13% in the international normalized ratio has been linked to the administration of
etoricoxib 120 mg once day in patients on long-term warfarin treatment (INR). As a result,
people using warfarin together with etoricoxib should have their INR regularly checked,
particularly after taking etoricoxib for the first time or having their dose changed (Schwartz et
al., 2007).

Digoxin

Healthy volunteers who received etoricoxib 120 mg once day for 10 days had a 33% rise in
digoxin Cmax; however, most patients would not typically find this increase to be significant.
When these medications are given together, individuals who are thought to be at high risk of
digoxin toxicity should be closely watched (Agrawal et al., 2008).

Rifampicin

Etoricoxib plasma AUC decreases by 65% when combined with rifampicin, a strong inducer
of hepatic metabolism. Rifampicin may also increase plasma levels of tacrolimus and lithium
or aggravate the nephrotoxic effects of cyclosporine. Therefore, when etoricoxib is used with
any of these drugs, renal function and blood lithium levels should be monitored (Patrignani et
al., 2003).

Acetylsalicylic acid

Etoricoxib does not interact with the antiplatelet action of low-dose aspirin, in contrast to
several other classic NSAIDs like ibuprofen and naproxen. It has been investigated if etoricoxib

8
may interfere with aspirin's irreversible inactivation of platelet COX-1. The inhibitory effects
of aspirin are not changed in healthy persons by steady-state plasma concentrations of
etoricoxib 120 mg per day for 12 days straight (Capone et al., 2005).

1.4.1 Indications

Selective COX-2 inhibitor etoricoxib is indicated for:

• Primary dysmenorrhea treatment: Primary dysmenorrhea is the period cramping that

occurs before or during the period.
• Osteoarthritis (OA) is a condition of the joints that may be treated. It results from the
cartilage at the ends of bones slowly degrading. Swelling (inflammation), pain,
soreness, stiffness, and incapacity are brought on by this.
• Rheumatoid arthritis (RA) treatment: Rheumatoid arthritis is a chronic inflammatory
condition of the joints. In the joints it affects, it produces discomfort, stiffness, edema,
and a progressive loss of mobility. Additionally, it could lead to inflammation in other
bodily parts.
• Ankylosing spondylitis (AS) treatment: AS is an inflammatory condition that affects
the spine and major joints.
• Care for gouty arthritis that is acute.
• The relief of gynecological pain after surgery.
• treatment for oral discomfort after surgery (Matsumoto and Cavanaughr, 2004).

1.4.2 Dosage and Administration

Etoricoxib is given orally and may be taken with or without meals. The beginning of the impact
of the medical product may be quicker when Etoricoxib is delivered without meals.
Recommended dosages are:

• Osteoarthritis: 30 or 60 mg once daily

• Rheumatoid arthritis: 90 mg once daily
• Gouty arthritis: A maximum of 8 days of treatment at the recommended dose of 120
mg once day should only be used during the acute unpleasant phase.
• Postoperative dental surgery pain: The recommended dose is 90 mg once day, with a
three-day therapeutic limit.
• Post-operative Gynecological Pain: The recommended dose is 90 mg once daily

9
 • Primary Dysmenorrhea: The recommended dose is 120 mg once daily (Daniels et al.,
2011).

1.5 Side Effects

Followings are the side effects of etoricoxib

• Gastritis (inflammation of the stomach's lining), heartburn, diarrhea, indigestion

(dyspepsia), stomach pain, nausea, vomiting, oesophageal inflammation, and mouth
ulcers.
• a quick or irregular pulse (palpitations), an irregular heart rhythm (arrhythmia).
• swollen legs and/or feet as a result of fluid retention (oedema).
• headaches and vertigo.
• an increase in blood pressure.
• Rough socket (inflammation and pain after a tooth extraction).
• wheeze or breathlessness (bronchospasms).
• Weakness and exhaustion (Kwiatkowska et al., 2017).

1.5.1 Contraindications

Etoricoxib is contraindicated in following conditions

• Heart failure that is congestive.

• Serious liver dysfunction.
• Patients who are allergic to other NSAIDs and have asthma, acute rhinitis, nasal
polyps, or urticarial.
• People who have high blood pressure, coronary artery disease, or cerebral vascular
disease.
• Approximately 30 mL/min of renal creatinine clearance.
• Bowel inflammation illness.
• Children and teenagers under the age of 16.
• Hypersensitivity (Capone et al., 2005).

10
1.5.2 Adverse Effect

Some common etoricoxib adverse effects is given below:

• Abdominal pain.
• Indigestion.
• Dizziness.
• Stomach upset.
• Swollen ankles.
• Bruising.
• Constipation or diarrhea (Capone et al., 2005).

1.6 Fertility, Pregnancy and Lactation

Fertility:

Etoricoxib, like any other medicine that inhibits COX-2, is not approved for women who are
seeking to conceive.

Pregnancy:

There are no academic research on babies who were exposed to etoricoxib. Studies on animals
have shown that it is bad for the reproductive system. Humans are in danger when pregnant.
Etoricoxib, like other prostaglandin-inhibiting drugs, may cause premature ductus arteriosus
closure and uterine inertia. Etoricoxib should not be used during pregnancy; if a woman
becomes pregnant, she must cease taking Etoricoxib right away.

Lactation:

It is unknown if etoricoxib is excreted in human milk. Etoricoxib is excreted in milk by

lactating rats. Etoricoxib shouldn't be used by nursing mothers (De Jong and Dolhain, 2017).

11
1.7 Quality Control Specifications

1.7.1 Weight Variation

The weight variation test is conducted by taking tablets, weighing each tablet individually,
getting the average weight, and then calculating the percent deviation. To ensure that each dose
includes the exact quantity of medications, weight variation is employed to measure dosage
forms. Weight fluctuation during compression is often caused by particle size dispersion and
insufficient powder or granule density. A weight variation test is necessary for tablets to verify
that variation in dosage and weight across tablets is maintained to a minimum. To enhance
tablet hardness and friability, tablet weights should be maintained within a particular range. To
carry out this test, 20 pills are individually weighed using a weight machine, and the average
weight is obtained. The weights of various pills are then compared. The outcome is displayed
as a percentage (Lachman et al., 1976).

(Individual Weight − Average weight)

% Weight Variation = × 100
Average Weight

Importance of weight variation test:

It is preferable that every tablet in a given batch weighs the same amount since uneven weight
might result in dosage fluctuation.

1.7.2 Hardness Test

It is a method used in laboratories to examine a tablet's structural stability and breaking point.

Importance of Hardness Test:

The ideal tablet hardness should be achieved because

• A tablet that is too firm may not disintegrate.

A tablet that is too soft may break during handling, packing, and transportation.

1.7.3 Disintegration Test:

The disintegration test is used to determine how quickly the tablet disintegrates. The
disintegration test stablishes how fast a tablet breaks into smaller particles providing a large
surface area and bioavailability of the medication when ingested by a patient. Disintegration
time is the main parameter to be tested in this test. The time it takes for a set of tablets to break

12
down into pieces small enough to pass through a 10mesh screen is measured by the
disintegration test based on a set of parameters. Tablet disintegration typically marks the
beginning of a drug's absorption from a solid dosage form following oral delivery.

Importance of Disintegration Test:

All coated and uncoated tablets should undergo a disintegration test since the rate at which a
medication dissolves relies on how long it takes to disintegrate, which in turn affects how
quickly a drug is absorbed.

1.7.4 Dissolution test

Dissolution is the process by which a medication moves from its solid dose form into the GI
fluid solution as a dissolved state. The rate-limiting step is the slowest in a drug's sequence of
kinetic steps.

Importance of Dissolution Test:

When a medication has extremely low water solubility, the rate at which it dissolves is often
the rate-limiting step, and hence has a rate-limiting influence on drug bioavailability. As a
result, drug dissolution testing is required.

1.7.5 Friability Test

This is the tendency of tablets to powder, chip, or fragment, which affects the aesthetic look,
customer acceptability of the tablet, and also contributes to tablet weight variance or contact
consistency issues. Friability testing is essential to establish how brittle a tablet will be during
manufacture, packaging, and transportation. This test uses twenty tablets in a USP Roche
friabilator set to 25 rpm for four minutes. If the weight loss is less than 1%, the tablets will pass
the friability test (V. R et al., 2014).

The % Friability Formula:

(Initial weight – final weight)

% Friability = × 100
Initial weight

The importance of the friability test:

This test is also used to determine the strength of the tablet. Friability is a quality associated
with tablet hardness. In the laboratory, a Roche Friabilator with a high rotational speed was
employed.

13
1.7.6 Potency Test

Potency testing is performed in order to determine the drug's therapeutic and harmful effects.
Potency tests are used to determine the amount of active drug available in a sample. The
potency range is 90-110. When it is crossing the limit, it will produce toxicity and when the
amount is below the limit, will caused sub-standard dosing.

% Potency = Drug present in a single tablet /Strength (mg)×100 (Gupta et al., 2014).

Importance of Potency Test:

The strength of the tablet should adhere to the specifications since very powerful drugs may
have harmful effects while extremely weak drugs may have ineffective effects.

1.8 Purpose of the Study

The aim of this study is to assess the quality control parameters of commercially available
Etoricoxib Tablets available in the market which was obtained from a model pharmacy in
Dhaka Bangladesh. All Tablets must be tested using the standard specification, weight
variation, diameter, thickness, disintegration time, hardness, friability and potency.

14
 Chapter -2
Materials and Methods

15
2. Study Outline:

The weight variation, hardness, diameter, friability, potency, thickness, disintegration time, and
dissolution profile of etoricoxib tablet brands available in Bangladesh were evaluated as part
of quality analysis.

2.1 Sample Collection:

For this analysis, a marketing sample of 20 etoricoxib tablets was purchased from a community
pharmacy in Farmgate, Dhaka. The samples were thoroughly examined for visual appearance,
manufacturing company, production date, expiration date, manufacturing license number,
batch number, and DAR number at the time of purchase.

2.2 Identification of Sample:

From the beginning date of manufacturing to the two-year expiration date, the whole tablet line
had a clearly indicated shelf life. The labeling on the Etoricoxib tablets said that each tablet
contained 90 mg of the drug. All of the tablets were packaged in blisters. The submitted branded
sample in table 1 was designated as Sample A.

Table 2.1: Label Information of Etoricoxib Tablets

Sl. Brand Drug Manufacturing Expiry DAR. Mfg.Lic Unit

.
No. Name Date No.
Name Date Price
No.
1 Coxia Etoricoxib 7/2021 7/2023 005-581-65 51 & 213 12.09

2.3 Reagents Used in The Experiment:

The comparative analysis of the etoricoxib tablets involves a few reagents. Table 2 lists
the reagents along with their uses and sources.

Table 2.2: Reagent Used in This Experiment

Reagents Use/Purpose Source

Etoricoxib Reference standard B. Pharm project lab

0.1N Hydrochloric Acid (HCl) Dissolution media B. Pharm project lab

16
 Distilled water For media preparation and B. Pharm project lab
dilution

Apparatus:

The apparatus used in the experiments are mentioned below:

• Pipette
• Pipette filler
• Conical flask
• Spatula
• Measuring cylinder
• Mortar & Pestle
• Class rod
• Stopwatch
• Test tube
• Test tube stand
• Filter paper
• Funnel
• Volumetric flask (10ml, 50ml, 100ml)
• UV-cell
• Beaker [250ml, 500ml, 1000ml]

2.4 Equipment Used in The In-Vitro Studies:

Table 2.3: Equipment Used for Different In-vitro Tests

In-Vitro Test Main Apparatus Manufacturer

Weight variation Electronic Analytic Balance Shimadzu Corporation, Japan

Thickness Digital Slide Calipers Mega Digital, China

Hardness Tablet Hardness Tester Veego, India

Friability Roche Friabilator VFT-2, India

Disintegration Tablet Disintegration Tester Electro lab, India

Dissolution USP dissolution apparatus II Electro lab, India

(Paddle apparatus)

17
 Potency UVmini-1240 spectrophotometer Shimadzu, Japan

2.5 Analytical Method:

This study helped to evaluate and compare the quality of oral etoricoxib tablets manufactured
by Bangladeshi pharmaceutical manufacturers. The following quality assessment meters are
used to evaluate the quality of twenty etoricoxib 90 mg tablets:

2.5.1 Weight Variation Test:

The weight variation test is an alternative to the content uniformity test of an analytical
weighing balance. Each tablet contains a certain quantity of medication as well as a unique
tablet composition. The weight variation test may be used to assess the quantity of medication
content in a tablet. The tablets are measured on a regular basis for this test. The electronic
balance by which weight variation is determined is shown in figure 4

Figure 2.1: Electronic Balance

18
Procedure: The procedure of weight variation test is given below:

• Twenty Etoricoxib tablets were taken like W1, W2, W3…...W20 and then weighted
each tablet individually by using an electronic balance.
• Then the average weight was determined by following equation: Average weight
=(W1+W2+W3+……. +W20)/ 20
• The percent deviation was determined by following way:

% deviation = (Individual weight – Average weight)/Average weight × 100

Table 2.4: Weight Variation Specification

Average Weight of Tablets (mg) Maximum Allowed % Deviation

Less than or equal 130 mg ±10%

130 to 324 mg ±7.5%

Greater than 324 mg ±5%

2.5.2 Measurement of Thickness and Diameter:

To manufacture tablets of similar thickness and diameter, the same fill, die, and pressure
parameters must be used during and between batch operations for the same formulation. The
amount of pressure exerted affects not just the thickness and breadth of the tablet, but also its
hardness. Controlling pressure is therefore critical for tablets with homogeneous thickness and
diameter. Tablet thickness and diameter are also important qualities in packing operations and
tablet counting using filling equipment that counts tablets based on consistent thickness and
diameter.

Tablet thickness and diameter are determined by

• The diameter of the die,

• During compression, the force or pressure is generated.,
• The maximum amount of fill that can be allowed into the die cavity and
• The compaction qualities of the fill material.

19
 Figure 2.2: Digital Slide Calipers

Procedure: The procedure of diameter measurement is given below:

• Twenty Etoricoxib tablets were taken like D1, D2, D3….D20 and then measure the
diameter of each tablet individually by using a digital slide calipers. The values were
reported in millimeter (mm).
• The average diameter was determined by the following formula: The average
diameter, D= (D1+D2+D3+ + D20)/20
• Then the % deviation were determined by using the following formula:

% deviation= (Individual Diameter- Average Diameter)/Average Diameter × 10

Thickness Measurement

Procedure: The procedure is given below:

• Twenty Etoricoxib tablets were taken like T1, T2, T3…..T20 and then measure the
thickness of each tablet individually by using a digital slide calipers. The values were
reported in millimeter (mm).
• The average thickness was determined by the following formula: The average
thickness, T= (T1+T2+T3+………+T20)/20
• Then the % deviation was determined by using the following formula:

% deviation = (Individual Thickness-Average Thickness) / Average Thickness ×100

According to USP, thickness of the tablet should be maintained within ±5%.

20
2.5.3 Hardness Test:

To do this test, three Etoricoxib tablets were put vertically in an automated hardness tester and
precisely set up. The equipment was then used to test the tablet's hardness, at which point the
tablet shattered. The tablets' hardness which was determined by using a tablet hardness tester.
It's written in kiloponds (kp) (Lachman, 1976).

The hardness tester is depicted in figure 6.

Figure 2.3: Hardness Tester

2.5.4 Friability Test:

Friability of tablets was measured by using Roche Friabilator. Friability was evaluated from
the percentage weight loss of 7 tablets. At first, 7 tablets were weighed and tumbled into
friabilator at 25 rpm for 4 minutes (100 revolutions). The tablets were then again weighed and
compared with their initial weights and percentage friability was calculated. Friability below
1% was considered acceptable. The percentage friability was then calculated by the following
formula:

% Friability = Initial Weight (W1)-Final Weight (W2)× 100 \ Initial Weight (W1)

Friability tester is shown in figure 2.4 below

21
 Figure 2.4: Friability Tester

2.5.5 Disintegration Test:

This test has great importance because a drug first undergoes disintegration and then
dissolves to give a solution for the attainment of bioavailability

Procedure

• The disintegration tester was filled with a 900 ml distilled water and temperature
was raised at 37 degrees Celsius.
• The machine was started.
• 3 tablets were placed into the chamber of the machine and disk was added.
• The disintegration time of each tablet was observed and noted carefully using a
stopwatch.
• The average disintegration time was measured with the following formula
Average DT= sum of disintegration time of individual tablets/number of tablets

The disintegration tester which is used for disintegration is shown in figure 2.5

22
 Figure 2.5: Disintegration Tester

Here table 2.5 shows the specifications of disintegration test according to USP

Table 2.5: Specifications of Disintegration Test According to USP

Types of Tablets Disintegration Time

Uncoated Tablets Not More Than 15 Minutes

Coated Tablets Not More Than 30 Minutes

Enteric Coated Tablets 2 hours in gastric fluid in (0.1N HCL)

and 1

hour in phosphate buffer (pH 6.8)

2.5.6 Dissolution Test:

The dissolution test is an in vitro test typically performed on oral dosage forms to measure the
performance of the drug products. The main principle of the dissolution equipment is that it
should provide gentle mixing that eventually leads to complete or near‐complete dissolution.
Method development is important for the dissolution method to avoid testing errors and to
prevent aberrant data. Manufacturing control is also a concern for the regulatory agencies;
therefore, variability among batches is carefully examined (Gray,2022).

23
 Figure 2.6: Dissolution Tester

Procedure:

In-Vitro dissolution test was performed by following standard procedure:

• At 100 rpm and 37±0.5°C temperature, the tablets were disintegrated using USP
apparatus -I (Basket type) in 900 ml 0.1 N Hcl as dissolution media.
• Three tablets of etoricoxib were placed in a separate dissolving tank.
• The test sample (10ml) was collected and changed with distilled water of equal volume
at predefined intervals (5, 15, 30, 45 and 60 minutes) and held at the same temperature.
• The material was collected, filtered and diluted ten times.
• The UV-Spectrophotometer was used to measure absorbance at 234 nm of the diluted
solutions against distilled water as a blank.

Release rate was presented as percent release by following equation

Cumulative Drug (mg)
% of durg release = × 100
Strength (mg)

24
Below Table 2.6 shows dissolution study parameter for Etoricoxib tablet

Table 2.6: Dissolution Study Parameter for Etoricoxib Tablet

Parameters Limits

Dissolution Medium 0.1N HCl

RPM 100

Apparatus USP apparatus 2

Temperature 37± 0.5ºC

λ max 234 nm

Time 60 min

2.5.7 Preparation of Standard Curve of Etoricoxib:

Determining the absorbance of a solution at a variety of known concentrations and plotting the
results to create a standard concentration curve with absorbance on the Y-axis and
concentration on the X-axis. Spectrophotometry is a technique for determining the absolute or
relative concentration of an analyte in a solution. We can obtain a y = mx+c (straight line)
formula by employing this technique. Make a basic concentration curve using known
concentrations before measuring the absorbance of the unknown concentration to determine
the absolute concentration of a specific compound. Placing a horizontal line parallel to the X-
axis and around the area on the Y-axis that connects to the absorbance can be used to determine
the unknown concentration from the standard curve. This line will cross the standard curve,
and a vertical line will be dragged to the X- axis at this point, where the concentration will be
recorded. When estimating undetermined or relative concentrations, two factors are crucial.
Because absorbance equals concentration but transmittance does not, the absorption maximum
should be utilized instead of percent transmittance. The absorbance is determined by UV
spectrophotometer is shown in figure 10:

25
 Figure 2.7: UV-Visible Spectrophotometer

Procedure:

• Etoricoxib 10 mg powder was precisely weighed and dissolved in 100 ml distilled water
it is the mother solution.
• Then 10 ml of mother solution was withdrawn and 90 ml 0.1N Hcl was added with it
and stock solution was prepared. Here 0.1 N Hcl is the media
• Then, absorbance of the stock solution was observed.
• The stock solution was collected and serially diluted up to 10 ml in ten test tubes.
• The diluted solutions from each test tube were taken and measured by UV-Vis
spectrophotometer by scanning the solutions at 234 nm wavelength.
• Then in MS-Excel, a graph of absorbance versus concentration is generated using the
collected data

2.5.8 Potency Determination:

Potency is a measurement for drug activity that describes the amount of a substance necessary
to generate a specific level of effect.

Potency determination for etoricoxib tablets were performed by following this standard
procedure.

Procedure:

• Firstly, four tablets of Coxia (Etoricoxib) were taken and total weight and average
weight of four tablets were calculated
• Then in a mortar and pestle, the four tablets of coxia were smashed properly.

26
 • A portion of the powder was dissolved in a media of 0.1 N Hcl and the solution was
filtered and absorbance was taken. The absorbance should be close to 1 and if not then
the solution was diluted. the absorbance of sample was observed using a UV Visible
Spectrophotometer at a wavelength of 234 nm and 0.1N HCI as a blank using a UV
Visible Spectrophotometer.
• Finally, the concentration of the medication was determined using the formula Y=
mx+c obtained from the standard curve and the percent (%) potency of the drug was
determined by using the following formula:

% potency = average weight ×conc(mg/ml) ×Df × total volume ×100 /sample taken × strength

Specification:

According to the USP, the tablet's potency should be no less than 95% and no more than 105
percent of the drug's listed dose.

27
 Chapter-3
Results and Discussion

28
3. Results and Discussion

3.1 Weight Variation Test

Weight variation was tested on 20 tablets to ensure uniformity of weight and fluctuation in
weight from tablet to tablet, which should be within the limits of % deviation according to USP
specification. Table 3.1 shows the weight variation of Etoricoxib tablets:

Table 3.1 Weight Variation of Etoricoxib tablets

SL Weight of Tablet Average Weight % of Deviation

(mg) (mg)
1 184 -1.473
2 187 0.134
3 187 0.134
4 187 0.134
5 186 -0.402
6 190 1.740
7 187 0.134
8 188 0.669
9 185 -0.937
10 191 2.276
11 187 186.75 0.134
12 190 1.740
13 188 0.669
14 188 0.669
15 186 -0.402
16 180 -3.614
17 178 -4.685
18 190 1.740
19 189 1.205
20 187 0.134

The average weight, maximum weight and minimum weight of Etoricoxib tablets are shown
in table 3.2:

29
 Table 3.2: The Average Weight, Maximum Weight and Minimum Weight of Etoricoxib
tablets

Brand Average Maximum Minimum Maximum % Minimum %

Name Weight Weight (mg) Weight (mg) Deviation Deviation
(mg)

Coxia 186.75 191 178 2.276 -4.685

The maximum and minimum percentages of deviation were also determined, and the number
of tablets showing the maximum and minimum percentages of deviation was recorded. Table
3.2 shows the maximum and minimum percentages of deviation, as well as showing the
average weight. The average weight of Etoricoxib tablets are shown in figure 3.1

Figure 3.1: Average Weight of Etoricoxib tablets

The maximum and Minimum % deviation of Etoricoxib tablets is shown in the following
Figure 3.2.

30
 Figure 3.2: Maximum and Minimum % of Deviation of Etoricoxib
tablets

As the average weight was stated between 130-324 mg, so the range of percent limit was ±7.5.
According to the results of this test, the % variations of this brand of Etoricoxib tablets were
within the specification.

3.2 Determination of Diameter and Shape

The diameter of a tablet is as important as the thickness and measured in the same way using
slide calipers. The table below shows the result obtained from the measurement of diameter of
each tablet of Coxia (Etoricoxib) . The observed results are shown in the following as shown
in Table 3.3.

31
 Table: 3.3: Average Diameter of Etoricoxib tablets

SL Diameter Average. Diameter % of Deviation

(mm) (mm)

1 8.05 0.012

2 8.05 0.012

3 8.05 0.012

4 8.05 0.012

5 8.03 -0.236

6 8.05 0.012

7 8.05 0.012

8 8.05 0.012

9 8.05 0.012

10 8.04 -0.112
8.05
11 8.05 0.012

12 8.05 0.012

13 8.05 0.012

14 8.05 0.012

15 8.06 0.137

16 8.05 0.012

17 8.05 0.012

18 8.05 0.012

19 8.05 0.012

20 8.05 0.012

32
Now the Average Diameter, Highest Diameter, and Lowest Diameter are shown in Table 3.4.

Table 3.4: The Highest Diameter and Lowest Diameter of Etoricoxib tablets

Brand Average Diameter (mm) Lowest Diameter (mm) Highest Diameter

Name (mm)

8.05 8.03 8.06

Coxia

Using the values from the Table 3.4, average diameter is shown in Figure 3.3.

Figure 3.3: The Average Diameter of Etoricoxib tablets

3.3 Determination of Thickness

Thickness of the tablets can vary without any change in the weight because of difference in
density of the granules and pressure applied to the tablets as well as the speed of tablets
compression. Table 3.5 shows the average thickness and % of deviation of Etoricoxib tablets:

33
 Table 3.5 Average Thickness and % of Deviation of Etoricoxib tablets

SL Thickness Average Thickness % of Deviation

(mm) (mm)

1 3.3 0.457

2 3.3 0.457

3 3.3 0.457

4 3.3 0.457

5 3.2 -2.588

6 3.3 0.457

7 3.3 0.457

8 3.3 0.457

9 3.3 0.457

10 3.2 3.29 -2.588

11 3.3 0.457

12 3.3 0.457

13 3.3 0.457

14 3.3 0.457

15 3.2 -2.588

16 3.3 0.457

17 3.3 0.457

18 3.3 0.457

19 3.3 0.457

20 3.3 0.457

34
Using the values from the Table 3.5, Maximum Thickness, Minimum Thickness and Highest
% of Thickness Deviation, and Lowest % of Thickness Deviation are shown in Table 3.6.

Table 3.6: The Maximum Thickness, Minimum Thickness and Highest % of Thickness
Deviation, and Lowest % of Thickness Deviation of Etoricoxib tablets

Brand Average Maximum Minimum Highest % of Lowest % of

Thickness Thickness Thickness Deviation Deviation
(mm) (mm) (mm)

Coxia 3.29 3.3 3.20 0.457 -2.588

Tablet thickness should be controlled within a ± 5% variation of a standard value. Figure

3.4 shows the average thickness of Etoricoxib tablets:

Figure 3.4: The Average Thickness of Etoricoxib tablets

3.4 Determination of Hardness

Tablet hardness refers to a tablet's resistance to capping, abrasion, or breaking during storage,
transit, and handling conditions. Other tablet characteristics such as density and porosity have
been linked to tablet hardness. Three tablets were chosen and the press at which every tablet
was crushed and recorded. Table 3.7 shows the average hardness (kp) of Etoricoxib tablets:

35
 Table 3.7: Hardness (kp) of Etoricoxib tablets

Brand Name Tab 1 Tab 2 Tab 3 Average SD

Coxia 8.5 8.06 8.04 8.20 0.212

According to this present study, the average hardness of Etoricoxib tablets was 8.20 kp. The
average hardness (kp) of Etoricoxib tablets are shown in the following Figure 3.5.

Figure 3.5: Average Hardness (kp) of Etoricoxib tablets

3.5 Determination of Friability

In the friabilator, seven weighed tablets are placed and rotated at 100 rpm for four minutes.
The tablets are then weighed and separated. The difference between the two weights is
determined by the ratio and as a percentage, the value of friability is provided. Friability of less
than 1% was considered acceptable. Table 3.8 shows the % of friability of Etoricoxib tablets:

Table 3.8: Etoricoxib tablets Friability Test

Total Tablets No. Initial Wt. (gm) Final Wt. (gm) % of Friability

7 1.303 1.300 0.23

36
 The percent friability is illustrated by the column diagram in Figure 3.6.

Figure 3.6: Percentage of Friability of Etoricoxib tablets

According to U.S.P specification, friability of tablets should not be greater than 1%. In our test,
the friability of Coxia tablets was obtained 0.23%. So, it can be said that, the value is within
limit.

3.6 Determination of Disintegration Time

The process of break-down of a tablet into smaller particles is called disintegration. It depends
on the hardness of the tablets and the use of binders during the granulation process. The In-
vitro disintegration time of a tablet was determined using the disintegration test apparatus. The
result is summarized in Table 3.9 and graphically represented in Figure 3.7:

Table 3.9: Disintegration Time of Etoricoxib Tablets

Brand Name Tab-1 Tab-2 Tab-3 Average SD

Coxia 5.22 4.5 4.53 4.75 0.333

37
 Figure 3.7: Graphical Representation of Disintegration Time

The average disintegration time was 4.75 minutes and a standard deviation of ± 0.333 % which
is within the range.

3.7 Determination of Standard Curve

Standard curve of Etoricoxib tablets was prepared by using reference standard Etoricoxib
provided by B. Pharm project lab. Initially, a solution of different concentrations of Etoricoxib
was prepared and then absorbance was taken at 234 nm by UV spectrophotometer. The
standard curve of the standard solution of Etoricoxib was obtained by plotting concentration
against absorbance. Table 3.10 shows the absorbance values of different concentrations of
Etoricoxib standard solutions:

Table 3.10: Determination of Absorbance

SL. Stock Solution (ml) Media (ml) Concentration (µg/ml) Absorbance

0 0 0 0 0

1 1 9 1 0.098

2 2 8 2 0.192

3 3 7 3 0.271

38
 4 4 6 4 0.346

5 5 5 5 0.411

6 6 4 6 0.485

7 7 3 7 0.564

8 8 2 8 0.593

9 9 1 9 0.757

10 10 0 10 0.838

In MS-Excel, a graph of absorbance versus concentration is generated using the collected data,
and the graph is shown in Figure 3.8. The line equation and regression coefficient were
obtained from that graph.

Figure 3.8: Graphical Representation of Standard Curve

39
 3.8 Determination of Potency

Potency is an important test, which is performed to ensure that the dosage form contains the
amount of API claimed by the manufacturer. According to the USP specification, the potency
of a tablet should be between 95-105 %. Table 3.11 shows the determination of potency of
Etoricoxib tablets:

Table 3.11: Determination of Potency of Etoricoxib tablets

Sample Taken
Tablet Weight

Strength (mg)
Total Volume
Absorbance

% Potency
Drug in a
Average

Tablet
Brand

mg/ml
µg/ml

DF

Coxia 0.796 9.796 0.0098 100 10 186.50 20.72 88.173 90 97.97

Potency of Etoricoxib tablets is shown in figure 3.9

Figure 3.9: Potency of Etoricoxib tablets

According to the USP, the potency should be within the range of 95-105%. Here, the sample
potency was measured at 97.97%. Based on the USP specification the sample tablets were
within the range.

40
3.9 Determination of Dissolution

When the temperature reached 37 degrees Celsius, one tablet was placed into the vessel and
the paddle was allowed to revolve. At specific time intervals (at 5,15, 30, 45 and 60 minutes),
the test sample (10ml) was withdrawn. Samples were collected, filtered, and analyzed using a
UV Spectrophotometer at 234 nm against a blank. The calibration curve was used to determine
the release rate as a percentage of drug release. The dissolution rate of three tablets were
measured. The percent of drug release in different consecutive time were obtained, the results
and average are shown in following table 3.12- 3.14 and 3.15.

Table 3.12: % of Drug Release of Etoricoxib tablets -Tablet 1

Time Absorbance µg /ml mg/ml DF mg/10 mg/900 Cumulative %

(min) ml ml Amount Release
Released

0 0 0 0 0 0 0 0 0
5 0.752 9.313 0.009 10 0.931 83.817 83.817 111.76
15 0.708 8.756 0.009 10 0.876 78.804 79.735 106.31
30 0.678 8.377 0.008 10 0.838 75.393 77.200 102.93
45 0.742 9.187 0.009 10 0.919 82.683 85.328 113.77
60 0.739 9.149 0.009 10 0.915 82.341 85.904 114.54

Table 3.13: % of Drug Release of Etoricoxib tablets -Tablet 2

Time Absorbance mcg/ mg/ml DF mg/10 mg/900 Cumulative %

(min) ml ml ml Amount Release
Released
0 0 0 0 0 0 0 0 0
5 0.654 8.073 0.008 10 0.807 72.657 72.657 96.88
15 0.735 9.098 0.009 10 0.910 81.882 82.689 110.25
30 0.704 8.706 0.009 10 0.871 78.354 80.071 106.76
45 0.739 9.149 0.009 10 0.915 82.341 84.929 113.24
60 0.689 8.516 0.009 10 0.852 76.644 79.339 105.79

41
 Table 3.14: % of Drug Release of Etoricoxib tablets -Tablet 3

Time Absorbance mcg/ mg/ml DF mg/10 mg/900 Cumulative %

(min) ml ml ml Amount Release
Released
0 0 0 0 0 0 0 0 0
5 0.549 6.744 0.007 10 0.674 60.696 60.696 80.93
15 0.781 9.681 0.010 10 0.968 87.129 87.803 117.07
30 0.777 9.630 0.010 10 0.963 86.670 88.313 117.75
45 0.731 9.048 0.009 10 0.905 81.432 84.038 112.05
60 0.801 9.934 0.010 10 0.993 89.406 92.916 123.89

Table 3.15: Percentage Drug Release Comparison of Three Tablets

Time (min) % Release % Release % Release Average

Tablet 1 Tablet 2 Tablet 3
0 0 0 0 0
5 111.76 96.88 80.93 96.52
15 106.31 110.25 117.07 111.21
30 102.93 106.76 117.75 109.15
45 113.77 113.24 112.05 113.02
60 114.54 105.79 123.89 114.74

The percentage of drug release of three tablets is shown in figure 3.10

42
 Figure 3.10: Percentage Drug Release Comparison of Three Tablets

According to USP, the percent release of drug from the tablets should not be less than 75% in
60 min. All the tested tablets in this study meet this specification.

The Average % Release of Three Tablets of Etoricoxib is shown in figure 3.11

Figure 3.11: Average % of Drug Release of Etoricoxib tablets

43
3.10 Conclusion

Pharmaceutical products must adhere to strict quality control standards because they directly
affect the patient's life. A pharmaceutical must guarantee that the product meets all standards
and is of the required quality to provide patients with the appropriate level of safety and
efficacy. Pharmaceuticals must be marketed as being stable, consistent formulations that are
clinically effective. Production of new and improved pharmaceuticals is increasing quickly. In
parallel, increasingly complex analysis approaches are being devised for their evaluation. The
pharmaceutical sector therefore adheres to international standards to guarantee the quality of
its products and to provide adequate safety and efficacy. A disintegration test, analysis of
weight variation, hardness, friability, and other quality-control criteria were evaluated in this
study.

44
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