Project Report

Comparative Study of Different Brands of
Olmesartan Tablets Available in Bangladesh
A dissertation submitted to the Department of Pharmacy,

State University of Bangladesh in the partial fulfillment of the
requirement for the degree of Bachelor of Pharmacy (Hons.)
Submitted By:
ID NO: UG08-33-18-008
Submission Date: September,2022

Contents
Abstract i
Chapter-01: Introduction
SI no. Topic Page No.

1.1 Olmesartan Tablet 1-6
1.2 Chemistry 6
1.3 History 7-8
1.4 Medical uses 8-9
1.4.1 Posology and Method Administration 9-11
1.4.2 Contraindications 11
1.5 Overdose 11-12
1.6 12
Pharmacodynamic properties
1.7 Pharmacokinetics properties 12-13
1.8 13-14
Fertility, pregnancy and lactation
1.8.1 Incompatibilities 14
1.8.2 Shelf life 14

1.8.3 Special precautions for storage 14
1.9 14
Nature and contents of container
1.9.1 Interaction with other medicinal products and forms of 14-15
interaction
1.9.2 Special warnings and precautions for use 15-16
Comparative Study of Different Brands of Olmesartan Tablets Available in Bangladesh

Contents
Chapter-02: Design of Investigation

2 Purpose of Drug 17
2.1 Aim of the work 18
2.1.1 Objective 18
2.2 Sample Collection 18
2.2.1 Sample Name 19
2.2.2 Test of quality control 19-20
Chapter-03: Materials and Methods

3.1 Materials 21
3.2 Equipments Used 21

3.3 21-22
Glass Wares Used
3.4 Methods 22-30

Contents
Chapter-04: Results
4.1 Weight Variation 31
4.2 Friability Test 32
4.3 Hardness Test 33
4.4 Disintegration Time Test 34-35
4.5 Preparation of Standard curve for Olmesartan 36-38
4.6 Dissolution time test 39-41
4.7 Determination of Potency 42-43
Chapter-05: Discussion
5.1 Weight Variation 44
5.2 Hardness and Friability 44
5.3 Disintegration Test 44
5.4 Dissolution Test 44-45
5.5 Potency Test 45
Chapter-06: Conclusion
6.0 Conclusion 46
Chapter-07: References
7.0 References 47-49

Abstract
Abstract
Choosing the proper drug product is getting complicated for health professionals and
patients due to the existence of abundant generic brands in local drug market with various
dosage forms of Olmesartan.In this study, evaluation of the quality parameters of some
local brands of Olmesartan (20mg) tablet was carried out. Ten brands (A1, A2, A3, A4,
A5,A6,A7,A8,A9&A10) of Olmesartan tablets (20mg) marketed in Bangladesh were
evaluated for eight in vitro tests including both official and unofficial viz. Weight variation,
friability, diameter, thickness, hardness, disintegration, potency was determined as well as
dissolution profile was evaluated using UV-spectroscopic method at 257 nm wavelength.
All the parameters were within the limited value. The present work reports the comparative
study and quality evaluation of tablets formulated by Ten different pharmaceutical
companies of Bangladesh The study was conducted to assess the quality of tablets through
the evaluation of weight variation, hardness, friability, disintegration, time, dissolution,
quality evaluation among commercially available brands of Olmesartan tablets in
Bangladesh. Study was conducted according to the proper standard of pharmacopoeia.
Tablets of ten manufactures were evaluated in ten groups. Observations were recorded
properly. Hardness and Friability of the tablets are an essential criterion in the determination
of the ability of the tablets to resist chipping, abrasion or breakage under conditions of
storage, transportation, handling and packaging. Hardness test results from 5.382 kg to
10.178 kg which is properly complied. Friability was between 0.022% to 0.052%, which
was properly complied. From the study it was identified that disintegration time of the tablet
was 1 min 18 sec to 2 min 20 sec (Water media), 58 sec to 2 min 08 sec (0.1N HCl media)
& 1 min 04 sec to 2 min 40 sec (Buffer media). All brands meet the specification and
disintegration time of all brands was within the limit. All Olmesartan tablets showed
acceptable weight variation as the percentage of weight variation were USP limits of ±
7.5% of average weight and acceptable friability (below 1%). Formulations were somewhat
different in their hardness, disintegration time. The in vitro dissolution tests were found
within the USP recommended limits for Olmesartan 20mg tablets. This study may help the
physicians, pharmacists and other medical professionals to know about some quality
parameters of different brands of Olmesartan tablets available in Bangladesh.

Page | i
Chapter 01: Introduction
Introduction
1.1 Olmesartan Tablet
Systematic (IUPAC) name: (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(1-
hydroxy-1-methylethyl)-2-propyl-1-{[2'-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}-
1H-imidazole-5-carboxylate
Olmesartan film-coated tablets are indicated for the treatment high blood pressure,
heart failure, and diabetic kidney disease. It is a reasonable initial treatment for
high blood pressure. It is taken by mouth. (Barakat, N.A., Maaty, S.H. and Al-
Koly)
Formula: C29H30N6O6
Molar mass: 558.6g/mol
Mechanism of action:
Olmesartan belongs to the angiotensin II receptor blocker (ARB) family of drugs,
which also includes telmisartan, candesartan, losartan, valsartan, and irbesartan.
ARBs selectively bind to angiotensin receptor 1 (AT1) and prevent the protein
Comparative Study of Different Brands of Olmesartan Available in Bangladesh Tablets

Page | 1
angiotensin II from binding and exerting its hypertensive effects. As the principal
pressor agent of the renin-angiotensin system, Angiotensin II causes
vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac
stimulation and renal reabsorption of sodium. Olmesartan blocks the
vasoconstrictor effects of angiotensin II by selectively blocking the binding of
angiotensin II to the AT1 receptor in vascular smooth muscle. Its action is,
therefore, independent of the pathways for angiotensin II synthesis.23 Overall,
olmesartan's physiologic effects lead to reduced blood pressure, lower aldosterone
levels, reduced cardiac activity, and increased excretion of sodium.
Olmesartan also effects on the renin-angiotensin aldosterone system (RAAS) plays

an important role in hemostasis and regulation of kidney, vascular, and cardiac
functions. Pharmacological blockade of RAAS via AT1 receptor blockade inhibits
negative regulatory feedback within RAAS, which is a contributing factor to the
pathogenesis and progression of cardiovascular disease, heart failure, and renal
disease. In particular, heart failure is associated with chronic activation of RAAS,
leading to inappropriate fluid retention, vasoconstriction, and ultimately a further
decline in left ventricular function. ARBs have been shown to have a protective
effect on the heart by improving cardiac function, reducing afterload, increasing
cardiac output and preventing ventricular hypertrophy and remodeling. (Bari, P.D.
and Rote, A.R)
Absorption:
When taken orally, the prodrug olmesartan medoxomil is rapidly absorbed in the
gastrointestinal tract and metabolized to olmesartan. The esterification with
medoxomil was created with the intention of increasing olmesartan bioavailability
from 4.5% to 28.6%. (Bhusari, K.P., Khedekar, P.B., Dhole, S. and Banode, V.S)
Metabolism:
Olmesartan medoxomil is rapidly and completely bioactivated by ester hydrolysis
to olmesartan during absorption from the gastrointestinal tract. This rapid first-pass
metabolism was confirmed by the lack of measurable amounts of olmesartan
medoxomil in plasma or excreta.1 This first-pass metabolism is not driven by
cytochrome enzymes and hence it is not expected to interact with other drugs via
this mechanism. (Brunner, H.R., 2002.)

Page | 2
Route of elimination:
The main elimination route of olmesartan is in the unchanged form through the
feces. From the systemically bioavailable dose, about 10-16% is eliminated in the
urine. (Lachman, M.E. and Tun, P.A., 2008.)
Adverse effect:
more common side effects that occur with olmesartan include:

back pain

diarrhea

headache

blood in your urine

high blood sugar

high triglycerides

flu-like symptoms, such as fever and body aches

sore throat, runny nose, and sinus infection

bronchitis
Serious effect:
Low blood pressure: This drug can cause your blood pressure to drop too low. If
you also take a diuretic (water pill) or if you’re dehydrated, you have a higher risk
of your blood pressure dropping too low. This may cause dizziness, lightheadedness,
and a headache.
Kidney damage: If you take olmesartan when your renin-angiotensin system is
activated, you risk serious kidney damage. This system is activated if you don’t have
enough fluid in your blood vessels. Your renin-angiotensin system is already active
if you have heart failure or renal artery stenosis, follow a low-salt diet, or are
dehydrated. Your doctor can tell you more.
Diarrhea and weight loss: If you take olmesartan for a long time (months to years),
it can cause severe, long-term diarrhea with weight loss. If you have diarrhea and
weight loss and your doctor can’t find another cause for it, you may need to stop
taking. (Celebier, M. and Altinoz, S., 2007.)

Page | 3
 Tabulated list of adverse reactions

Adverse reactions from olmesartan in clinical trials, post-authorization safety
studies and spontaneous reporting are summarized in the below table.
The following terminologies have been used in order to classify the occurrence of
adverse reactions very common (≥1/10); common (≥1/100 to <1/10); uncommon
(≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000);
not known (cannot be estimated from the available data). (Chrysant, S.G., Melino,
M., Karki, S., Lee, J. and Heyrman, R., 2008.)
Table of adverse reaction:

System Organ Class Adverse Reactions Frequency
Blood and lymphatic Thrombocytopenia Uncommon

system disorders
Immune system Anaphylactic reaction Uncommon

disorders
Metabolism and Hypertriglyceridaemia Common

nutrition disorders
Hyperuricaemia Common
Hyperkalaemia Rare
Nervous system Dizziness Common

disorders
Headache Common
Ear and labyrinth Vertigo Uncommon

disorders
Cardiac disorders Angina pectoris Uncommon
Vascular disorders Hypotension Rare
Respiratory, thoracic and Bronchitis Common

mediastinal disorders
Pharyngitis Common
Cough Common

Page | 4
Rhinitis Common
Gastrointestinal Gastroenteritis Common

disorders
Diarrhea Common
Abdominal pain Common
Nausea Common
Dyspepsia Common
Vomiting Uncommon
Sprue-like enteropathy (see Very rare

section 4.4)
Hepatobiliary disorders Autoimmune hepatitis* Not known
Skin and subcutaneous Exanthema Uncommon

tissue disorders
Allergic dermatitis Uncommon
Urticaria Uncommon
Rash Uncommon
Pruritus Uncommon
Angioedema Rare
Musculoskeletal and Arthritis Common

connective tissue
disorders Back pain Common
Skeletal pain Common
Myalgia Uncommon
Muscle spasm Rare
Renal and urinary Haematuria Common

disorders
Urinary tract infection Common
Acute renal failure Rare

Page | 5
Renal insufficiency Rare
General disorders and Pain Common

administration site
conditions Chest pain Common
Peripheral oedema Common
Influenza-like symptoms Common
Fatigue Common
Face oedema Uncommon
Asthenia Uncommon
Malaise Uncommon
Lethargy Rare
Investigations Hepatic enzymes increased Common
Blood urea increased Common
Blood creatine phosphokinase Common

increased
1.2 CHEMISTRY
Chemical data:
Formula C29H30N6O6
Mol.mass 558.595g.mol-1

Page | 6
1.3 History
Olmesartan belongs to the angiotensin II receptor blocker (ARB) family of drugs,

which also includes telmisartan, candesartan, losartan, valsartan, and irbesartan.
ARBs selectively bind to angiotensin receptor 1 (AT1) and prevent the protein
angiotensin II from binding and exerting its hypertensive effects, which include
vasoconstriction, stimulation and synthesis of aldosterone and ADH, cardiac
stimulation, and renal reabsorption of sodium, among others. Overall, olmesartan's
physiologic effects lead to reduced blood pressure, lower aldosterone levels,
reduced cardiac activity, and increased excretion of sodium.
Olmesartan also affects the renin-angiotensin aldosterone system (RAAS), which

plays an important role in hemostasis and regulation of kidney, vascular, and cardiac
functions. Pharmacological blockade of RAAS via AT1 receptor blockade inhibits
negative regulatory feedback within RAAS, which is a contributing factor to the
pathogenesis and progression of cardiovascular disease, heart failure, and renal
disease. In particular, heart failure is associated with chronic activation of RAAS,
leading to inappropriate fluid retention, vasoconstriction, and ultimately a further
decline in left ventricular function. ARBs have been shown to have a protective effect
on the heart by improving cardiac function, reducing afterload, increasing cardiac
output and preventing ventricular hypertrophy and remodelling.4
By comparison, the angiotensin-converting enzyme inhibitor (ACEi) class of

medications (which includes drugs such as ramipril, lisinopril, and perindopril)
inhibit the conversion of angiotensin I to angiotensin II through inhibition of the
ACE enzyme. However, this does not prevent the formation of all angiotensin II
within the body. The angiotensin II receptor blocker (ARB) family of drugs unique
in that it blocks all angiotensin II activity, regardless of where or how it was
synthesized.
Olmesartan is commonly used for the management of hypertension and Type 2

Diabetes-associated nephropathy, particularly in patients who are unable to tolerate
ACE inhibitors. ARBs such as olmesartan have been shown in a number of large-
scale clinical outcomes trials to improve cardiovascular outcomes including
reducing risk of myocardial infarction, stroke, the progression of heart failure, and
hospitalization.5,6,7,8,9,10,11,12 Like other ARBs, olmesartan blockade of RAAS
slows the progression of diabetic nephropathy due to its renoprotective
effects.13,14,15

Page | 7
Orally available olmesartan is produced as the prodrug olmesartan medoxomil

which is rapidly converted in vivo to the pharmacologically active olmesartan.1 It
was developed by Daiichi Sankyo Pharmaceuticals and approved in 2002.
(Chrysant, S.G., Weber, M.A., Wang, A.C. and Hinman, D.J., 2004.)
1.4 Medical uses:

Before taking olmesartan:

you should not take olmesartan if you are allergic to it.

If you have diabetes, do not use olmesartan together with any medication that
contains aliskiren (a blood pressure medicine).

You may also need to avoid taking olmesartan with aliskiren if you have
kidney disease.
Tell your doctor if you have ever had:


a heart condition other than one being treated with olmesartan;

kidney disease; or

if you are on a low salt diet.
Do not use if you are pregnant. Stop using the medicine and tell your doctor right
away if you become pregnant. Olmesartan can cause injury or death to the unborn
baby if you take the medicine during your second or third trimester.
If you plan to get pregnant, ask your doctor for a safer medicine to use before and
during pregnancy. Having high blood pressure during pregnancy may cause
complications in the mother and the baby.
You should not breastfeed while using olmesartan. (Kamble, A.Y., Mahadik,
M.V., Khatal, L.D. and Dhaneshwar, S.R., 2010.)
How to take olmesartan:

Follow all directions on your prescription label and read all medication
guides or instruction sheets. Your doctor may occasionally change your
dose. Use the medicine exactly as directed.

You may take olmesartan with or without food.

Page | 8

For a child who cannot swallow a tablet whole, a pharmacist can mix the
medicine into a liquid.

Shake the liquid before you measure a dose. Use the dosing syringe provided,
or use a medicine dose-measuring device (not a kitchen spoon).

Olmesartan doses are based on weight in children and/or teenagers. Your
child's dose needs may change if the child gains or loses weight.

Call your doctor if you are sick with vomiting or diarrhea, or if you are
sweating more than usual. You can easily become dehydrated while taking
olmesartan.

It may take up to 2 weeks before your blood pressure is under control.
Keep using this medicine as directed, even if you feel well. High blood
pressure often has no symptoms.

You may need to use blood pressure medicine for the rest of your life.
Treatment may also include diet, exercise, lowering cholesterol, not
smoking, and controlling diabetes.

Your blood pressure will need to be checked often. Your kidney function may
also need to be checked.

Store tablets at room temperature away from moisture and heat.

Store the liquid in a refrigerator. Throw away any liquid leftover after 4
weeks.
(Koike, H., Sada, T. and Mizuno, M., 2001.)
1.4.1 Posology and Method Administration:
Olmesartan film-coated tablets are supplied for oral administration and should be
swallowd whole with a sufficient quantity of liquid.
To be taking preferably with or after food. When olmesartan was administration to

fasting and fed healthy volunteers only the rate and not the extent of olmesartan
adsorption was affected.

Page | 9
Undesirable effects may be minimized by using the lowest effective doses for the
shortest duration necessary to control symptoms.
Adults:

20 mg orally once a day; may increase dose to 40 mg in two weeks if
further blood pressure reduction is needed.

Maximum dose: 40 mg orally once a day.
Childs:
 Children 6 to 16 years of age weighing at least 20 kg and less than 35 kg—

Dose is based on body weight and must be determined by your doctor. The
dose is usually 10 to 20 mg once a day. If the child cannot swallow the
tablets, an oral suspension is recommended.
 Children 1 to 5 years of age—Use and dose must be determined by your

doctor.
 Children younger than 1 year of age—Use is not recommended.
Elderly:
Older people (65 years or older)
No adjustment of dosage is generally required in older people (see below for dose
recommendations in patients with renal impairment). If up-titration to the
maximum dose of 40mg daily is required, blood pressure should be closely
monitored.
Renal impairment:
The maximum dose in patients with mild to moderate renal impairment (creatinine
clearance of 20 – 60 mL/min) is 20 mg olmesartan medoxomil once daily, owing
to limited experience of higher dosages in this patient group. The use of
olmesartan medoxomil in patients with severe renal impairment.
Hepatic impairment:
No adjustment of dosage recommendations is required for patients with mild

hepatic impairment. In patients with moderate hepatic impairment, an initial dose
of 10 mg olmesartan medoxomil once daily is recommended and the maximum

Page | 10
dose should not exceed 20 mg once daily. Close monitoring of blood pressure and
renal function is advised in hepatically-impaired patients who are already
receiving diuretics and/or other antihypertensive agents. There is no experience of
olmesartan medoxomil in patients with severe hepatic impairment, therefore use
is not recommended in this patientgroup. Olmesartan medoxomil should not be
used in patients with biliary obstruction.
Method of administration:
In order to assist compliance, it is recommended that Olmesartan medoxomil

tablets be taken at about the same time each day, with or without food, for example
at breakfast time. The tablet should be swallowed with a sufficient amount of fluid
(e.g. one glass of water). The tablet should not be chewed.
1.4.2 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Second and third trimesters of pregnancy.

Biliary obstruction.

The concomitant use of Olmesartan medoxomil with aliskiren-containing
products is contraindicated in patients with diabetes mellitus or renal
impairment (GFR < 60 ml/min/1.73 m2
(Laeis, P., Püchler, K. and Kirch, W., 2001)
1.5 Overdose
Symptoms of overdose
 Blurred vision
 chest pain or discomfort
 dizziness, faintness, or lightheadedness
 sweating
Some side effects may occur that usually do not need medical attention. These side
effects may go away during treatment as your body adjusts to the medicine. Also,

Page | 11
your health care professional may be able to tell you about ways to prevent or
reduce some of these side effects. Check with your health care professional if any
of the following side effects continue or are bothersome or if you have any
questionsabout them.
1.6 Pharmacodynamic properties

Pharmacotherapeutic group: Angiotensin II antagonists, ATC code: C09C A 08.
Mechanism of action / Pharmacodynamic effects:
Olmesartan medoxomil is a potent, orally active, selective angiotensin II receptor

(type AT1) antagonist. It is expected to block all actions of angiotensin II mediated
by the AT1 receptor, regardless of the source or route of synthesis of angiotensin
II. The selective antagonism of the angiotensin II (AT1) receptors results in
increases in plasma renin levels and angiotensin I and II concentrations, and some
decrease in plasma aldosterone concentrations.
Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-

aldosterone system and plays a significant role in the pathophysiology of
hypertension via the type 1 (AT1) receptor. (Laeis, P., Püchler, K. and Kirch, W.,
2001.)
1.7. Pharmacokinetic properties

Absorption and distribution:
Olmesartan medoxomil is a prodrug. It is rapidly converted to the

pharmacologically active metabolite, olmesartan, by esterases in the gut mucosa
and in portal blood during absorption from the gastrointestinal tract.
No intact olmesartan medoxomil or intact side chain medoxomil moiety have been
detected in plasma or excreta. The mean absolute bioavailability of olmesartan
from a tablet formulation was 25.6%.
mean peak plasma concentration (Cmax) of olmesartan is reached within about 2

hours after oral dosing with olmesartan medoxomil, and olmesartan plasma
concentrations increase approximately linearly with increasing single oral doses up
to about 80 mg.
Food had minimal effect on the bioavailability of olmesartan and therefore

olmesartan medoxomil may be administered with or without food.

Page | 12
No clinically relevant gender-related differences in the pharmacokinetics of

olmesartan have been observed.
Olmesartan is highly bound to plasma protein (99.7%), but the potential for
clinically significant protein binding displacement interactions between olmesartan
and other highly bound coadministered drugs is low (as confirmed by the lack of a
clinically significant interaction between olmesartan medoxomil and warfarin).
The binding of olmesartan to blood cells is negligible. The mean volume of
distribution after intravenous dosing is low (16 – 29 L). (Laeis, P., Püchler, K. and
Kirch, W., 2001.)
1.8. Fertility, pregnancy and lactation

Pregnancy:
The use of angiotensin II antagonists is not recommended during the first trimester
of pregnancy. The use of angiotensin II antagonists is contra-indicated during the
2nd and 3rd trimester of pregnancy.
Epidemiological evidence regarding the risk of teratogenicity following exposure

to ACE inhibitors during the first trimester of pregnancy has not been conclusive;
however, a small increase in risk cannot be excluded. Whilst there is no controlled
epidemiological data on the risk with angiotensin II antagonists, similar risks may
exist for this class of drugs. Unless continued angiotensin receptor blocker therapy
is considered essential, patients planning pregnancy should be changed to
alternative anti-hypertensive treatments which have an established safety profile
for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II
antagonists should be stopped immediately, and, if appropriate, alternative therapy
should be started.
Angiotensin II antagonist’s therapy exposure during the second and third

trimesters is known to induce human fetotoxicity (decreased renal function,
oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure,
hypotension, hyperkalaemia).
Should exposure to angiotensin II antagonists have occurred from the second

trimester of pregnancy, ultrasound check of renal function and skull is
recommended. Infants whose mothers have taken angiotensin II antagonists should
be closely observed for hypotension.

Page | 13
Breast-feeding:
Olmesartan is excreted in the milk of lactating rats but it is not known whether
olmesartan is excreted in human milk. Because no information is available regarding
the use of Olmesartan during breast-feeding, Olmesartan is not recommended and
alternative treatments with better established safety profiles during breast-feeding are
preferable, especially while nursing a newborn or preterm infant. (Laeis, P., Püchler,
K., Sudhop, T., Schwocho, L.R. and Gonzalez, L., 2001.)
Fertility:
There's no evidence that olmesartan reduces fertility in men or women. But speak
to a pharmacist or your doctor before taking it if you're trying to get pregnant.
(Laeis, P., Püchler, K., Sudhop, T., Schwocho, L.R.)
1.8.1 Incompatibilities
Not applicable
1.8.2 Shelf life

2 years.
1.8.3 Special precautions for storage

This medicinal product does not require any special storage conditions.
1.9 Nature and contents of container

Aluminium/aluminium blister pack. Packs of 7, 10, 14, 28, 30, 56, 60, 84, 90, 98
and 100 film-coated tablets. Not all pack sizes may be marketed
1.9.1. Interaction with other medicinal products and other

forms of interaction
The blood pressure lowering effect of olmesartan medoxomil can be increased by
concomitant use of other antihypertensive medications.
ACE-inhibitors, angiotensin II receptor blockers or aliskiren
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-
system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor
blockers or aliskiren is associated with a higher frequency of

Page | 14
adverse events such as hypotension, hyperkalaemia and decreased renal function

(including acute renal failure) compared to the use of a single RAAS-acting agent.
Potassium supplements and potassium sparing diuretics:
Based on experience with the use of other drugs that affect the renin-angiotensin
system, concomitant use of potassium-sparing diuretics, potassium supplements,
salt substitutes containing potassium or other drugs that may increase serum
potassium levels (e.g. heparin) may lead to increases in serum potassium. Such
concomitant use is therefore not recommended.
Non-steroidal anti-inflammatory drugs (NSAIDs):
NSAIDs (including acetylsalicylic acid at doses> 3 g/day and also COX-2

inhibitors) and angiotensin II receptor antagonists may act synergistically by
decreasing glomerular filtration. The risk of the concomitant use of NSAIDs and
angiotensin II antagonists is the occurrence of acute renal failure. Monitoring of
renal function at the beginning of treatment should be recommended as well as
regular hydration of the patient.
Additionally, concomitant treatment can reduce the antihypertensive effect of

angiotensin II receptor antagonists, leading to their partial loss of efficacy.
(Murakami, T., Konno, H., Fukutsu, N., Onodera, M., Kawasaki, T. and Kusu, F.,
2008.)
1.9.2 Special warnings and precautions for use

Intravascular volume depletion:
Symptomatic hypotension, especially after the first dose, may occur in patients
who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt
restriction, diarrhoea or vomiting. Such conditions should be corrected before the
administration of olmesartan medoxomil.
Other conditions with stimulation of the renin-angiotensin-aldosterone system:
In patients whose vascular tone and renal function depend predominantly on the
activity of the renin-angiotensin-aldosterone system (e.g. patients with severe
congestive heart failure or underlying renal disease, including renal artery stenosis),
treatment with other drugs that affect this system has been associated with acute
hypotension, azotaemia, oliguria or, rarely, acute renal failure. The possibility of
similar effects cannot be excluded with angiotensin II receptor antagonists.

Page | 15
Renovascular hypertension:
There is an increased risk of severe hypotension and renal insufficiency when

patients with bilateral renal artery stenosis or stenosis of the artery to a single
functioning kidney are treated with medicinal products that affect the renin-
angiotensin-aldosterone system.
Renal impairment and kidney transplantation:
When olmesartan medoxomil is used in patients with impaired renal function,

periodic monitoring of serum potassium and creatinine levels is recommended.
Use of olmesartan medoxomil is not recommended in patients with severe renal
impairment (creatinine clearance < 20 ml/min) (see sections 4.2 and 5.2). There is
no experience of the administration of olmesartan medoxomil in patients with a
recent kidney transplant or in patients with end-stage renal impairment (i.e.
creatinine clearance < 12 ml/min).
Hepatic impairment:
There is no experience in patients with severe hepatic impairment and therefore use of
olmesartan medoxomil in this patient group is not recommended (see section 4.2 for
dosage recommendations in patients with mild or moderate hepatic impairment).
Hyperkalaemia:
The use of medicinal products that affect the renin-angiotensin-aldosterone system

may cause hyperkalaemia. (Oparil, S., Melino, M., Lee, J., Fernandez, V.2010)

Page | 16
Chapter 02: Drug of Investigation
2. Purpose of Drug
Bangladesh is a developing country; majority of population are below the poverty line.
Hence, they prefer to go for low priced medicines. To reduce the cost of medicines
especially for the below poverty line group of developing countries, the World Health
Organization (WHO) has continuously supported the use of generic drug products,
aiming to improve the overall health care system. The generic substitution could be
considered when a generic copy of a reference drug contains identical amounts of the
same active ingredient in the same dose formulation and route of administration as
well as meet standards for strength, purity, quality, and identity. Although, the WHO
issued guidelines for global standardization and requirements for the registration,
assessment, marketing, authorization and quality control of generic drug products.
The generic products are usually far cheaper than its branded versions as generic
manufacturers do not have the investment costs for the development of a new drug. To
assist in substitution of branded with generics for affordability and at the same time
achieve therapeutic efficacy, bioequivalence studies become paramount.
Bioequivalence has been described as the absence of a significant difference in the rate
and extent to which the active moiety in pharmaceutical equivalents or pharmaceutical
alternatives become available at the site of drug action (i.e., a significant difference in
the bioavailability of two drug products) when they are administered at the equal
molar dose under similar conditions in an appropriately designed study. Two
pharmaceutical products are considered to be bioequivalent when their bioavailability
factors (from the same molar dose) are so similar that they are unlikely to produce
clinically relevant differences in therapeutic and/or adverse effects. Bioequivalence
studies involve both in vivo and in vitro studies. With the introduction of
biopharmaceutics classification system (BCS), in vivo bioequivalence studies could be
waived for immediate release solid oral dosage forms for class I (high solubility and
high permeability) and class III (high solubility and low permeability). Therefore, only
in vitro testing may be utilized to determine bioequivalence for highly soluble and
highly permeable drugs. Dissolution testing can serve as a tool to distinguish between
acceptable and unacceptable drug products. It is a surrogate marker for bioequivalence
test is a practical and economic approach in developing countries, where both
technology and resources are limited for in vivo studies. (Strawn, W.B., Chappell,
M.C., Dean, R.H., Kivlighn, S. and Ferrario, C.M., 2000.)
The drug release from a drug product (i.e., drug dissolution) under physiological
conditions and the permeability across the Pain relief determines the drug absorption.
Thus, in vitro dissolution may be vital in assessing in vivo performances.

Page | 17
2.1 Aim of the work

Aim of this study is to determine the potency of drug available in our market ,we need
a specific amount to have therapeutic effect in human body. Olmesartan is a common
drug and almost an Over the Counter (OTC) drug in Bangladesh thus it has high risk.
Potency determination was performed to evaluate that the marketed samples comply
with the declared specification or not. Dissolution was performed to see that if potency
is high but the drug is not bio-available. Hardness is also checked to see that whether it
interfere with the dissolution which ultimately effect the bioavailability. (Sanford,
Mark, and Susan J. Keam.)
2.1.1 Objective

To identify formulation excipients based on compatibility studies.

To Optimize formulation and processing parameters (Stirring speed, Viscosity
of oil phase and Percentage of emulsifying agent, etc.) using optimization
technique (Response Surface Methodology) to get the desired response
(particle size, entrapment efficiency and drug release).

To predict the optimized formulation based on the desired response obtained.

To prepare the olmesartan micro particles based on predicted optimized
formulation.

To evaluate the product through various in-vitro (entrapment efficiency, drug
content, surface characteristics, particle size, drug release & stability) and in-
vivo (safety, bioavailability & efficacy) studies.
2.2 Sample Collection

Ten brands of marketed (production date not more than three months ago from the
purchase) olmesartan tablets were obtained from various drug stores. The samples were
properly checked their Manufacturer Name, Physical appearance, Batch number, and
date of manufacture and expiry dates before purchasing. The labeled active ingredient
of olmesartan Tablets was 20mg and packaged in strip or in blister packing.

Page | 18
2.2.1 Sample Name

The maximum retail prices of all this brand tablets were in between 7 to 15 Taka for
each pieces except others. Each piece of Olmesartan tablets are 8 Taka, in Bangladeshi
currency.
S. N. Brand Name Sample Manufacturer Name

Code
01 Olsart 20mg A1 Opsonin Pharma Limited
02 Orbas 20mg A2 ACME Laboratories Limited
03 Presulock 20mg A3 Aristopharma Limited
04 Abetis 20mg A4 ACI Limited
05 Olmecar 20mg A5 Square Pharmaceuticals Limited
06 Olmevas 20mg A6 Popular Pharmaceuticals Limited

07 Olmesafe 20mg A7 Orion Pharma Limited
08 Olmesta 20mg A8 Eskayef Pharmaceuticals Limited
09 Olmezest 20mg A9 Sun Pharmaceuticals Limited
10 Olmepres 20mg A10 General Pharmaceuticals Limited
2.2.2 Test of quality control

In general-terms, quality control refers to a procedure or a set of steps taken during the
manufacturing of a product to ensure that it meets requirements and that the product is
reproducible. To ensure the quality and potency of the product some analytical
examinations. Have to done. When these examinations are done to control the quality
during production and verified after production, hence called in process control (IPC).

Page | 19
These examinations can be classifying in to two parts:
1. Official Tests:
I. Uniformity of Weight Determination
II. Disintegration Time
III. Dissolution Rate
IV. Drug Content/ Assay
2. Non Official Tests:

I. Hardness Test
II. Friability Test
Tablet description test is done by visual observation

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Chapter 03: Materials and Methods
3.1 Materials
The study was done by performing various test procedure associated to assess the quality of
tablets. Quality control parameters of ten commercially available Olmesartan tablet brands in
Bangladesh were used in the study.
3.2 Equipments Used
All the used equipments throughout the project are listed in the following table along with their
source of origin.
Name Model Source
UV-VIS Spectrophotometer UV-1800 Pharma Spec. Simadzu Corporation, Japan
Automated Eight Basket UDA-80 USP Standard Veego, India

Tablet Dissolution Tester
Electronic Balance AL 204 Mettler Toledo, Japan
Hot Air Oven Labtech Daihan, Korea
Disintegration Tester Veego India
Digital Tablet Hardness Test Veego India

Apparatus
Friability Tester Veego VFT-2D India
All the machines were operating perfectly. Equipments were free from dust and other
unnecessary particles.
3.3 Glass Wares Used
All the used glassware throughout the project work are listed in the following table along with
their source of origin.

Page | 21
Name Source
Pipette (10 ml, 5ml, 1ml) China
Beaker China
Test Tubes China
Funnel China
Sintered Glass Filter Germany
Volumetric Flask (5ml, 50ml) Bangladesh
Measuring Cylinder China
Filter Paper (No.41) England
Glassware’s were cleaned, and free from unnecessary particles.
3.4 Methods
Tablet Description: The color, shape and size were examined by visual observation.
Uniformity of Weight Determination: Ten tablets from each of the Ten brands were weighed
individually using a Metter AL 204 weighing balance. The average weights of the tablet were
calculated as well as their percentage deviation from the average weight.
Method: Weight 10 tablets selected at random, each one individually like x1, x2, x3.x10.
Determine the average weight: x= x1+ x2+ x3+………. +x10/10
Not more than 2 of the individual weight deviate from the average weight (x) by more than the
(%) deviation given below & none deviates by more than twice that %.
Limits:
Weight of the 80 mg or less then % deviation = ±10%.
Weight of tablets >80 - <250 mg then % deviation = ±7.5%
Weight of tablets 250 mg or more then % deviation = ± 5%

Page | 22
Figure 4.1: Electric Balance ( AL 204, Mettler Toledo, Japan)
Friability Test: Ten tablets were weighed and subjected to abrasion using Veego tablet
friability tester (Model VFT – 2D, India) at 25 rev / minute. The tablets were weighed after
four minutes and the weight compared to the initial weight.
It is the tendency of tablets to powder; chip or fragment and this can affect the elegance
appearance, consumer acceptance of the tablets, and add to tablets weight variation, or content
uniformity problems. The tablet may well be subjected to a tumbling motion. For example,
Coating packaging transport, which are not severe enough to break the tablets, but may abrade
the small particle from tablet surface? To examine this, tablets are subjected to a uniform
tumbling motion for specified time and weight loss is measured. Friability is properties that is
related to the hardness of the tablet & also add weight variation, content uniformity problems.
An instrument called friabilator is used to evaluate the ability of the tablet to withstand abrasion
in packaging, handling and shipping.
Method:
Weight 10 tablets altogether=W1
Put these tablets in the friabilator and adjust the instrument at 5 rpm (i.e. 25 rpm for 4 min)

Page | 23
Weight the 10 tablets (only the intact ones) =W2
Figure 4.2: Friability Tester (Model: Veego VFT-2D, India)
Limit: Friability (% loss) = Not more than 1% or equal to 1%
Hardness Test: It is the load required to crush the tablet when placed on its edge. This
crushing strength was determined using a Veego tablet hardness tester. We measure hardness to
determine the need for pressure adjustments on the tableting machine. Hardness can affect the
disintegration.
So, if the tablet is too hard, it may not disintegrate in the required period of time and if the
tablet is too soft it will not withstand the handling during subsequent processing such as coating
and packaging.
Method: Measurement is carried out on 10 tablets taking care to remove all the fragments of
the broken tablets before each determination and then take the average hardness.

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Figure 4.3: Digital Tablet Hardness Test Apparatus (Veego, India)
Limit: Normally tablet hardness ranges from 4-10 kg (1kg = 10 Newton).
Factors Affecting Hardness:
 Compression of tablet and compressive force.
 Amount of binder (more binder, more hardness)
 Method of granulation in preparing the tablet (wet method gives the best hardness)
Tablet Disintegration Test: This was determined at 37oC using Veego disintegration testing
apparatus until no particle remained on the basket of the system. The time taking for each of the
four tablets tested in each of the brand was recorded.
It is the time required for the tablet to break into particles, the disintegration test is a measure
only of the time required under a given set of conditions for a group of tablets to disintegrate
into particles.
For Amlodipine tablets, media was water at 37oC, the movement of apparatus in the media is
called peristaltic movement, similar to stomach movement.
Limit: Put the tablets in the apparatus in water or HCl for 30 minutes at 37oC (according to the
U.S.P.). If not disintegrated, put in intestinal fluid.

Page | 25
Figure 4.4: Disintegration Tester (Veego, India)
Dissolution rate determination: This was determined using the Veego UDA-80 USP Standard
dissolution rate testing apparatus using 0.1M HCl (900 ml) as the dissolution medium.
The release of drug from the tablet into solution per unit time under standardize condition is
called dissolution test.
Media used in dissolution testing may be purified water, simulated gastric fluid, simulated
intestinal fluid or others. Organic solvents are not recommended.
There are four dissolution apparatuses standardized and specified. They are:
 USP Dissolution Apparatus 1 - Basket (37°C)
 USP Dissolution apparatus 2- Paddle (37°C)
 USP Dissolution Apparatus 3 - Reciprocating Cylinder (37°C)
 USP Dissolution Apparatus 4 - Flow-Through Cell (37°C)
USP Dissolution Apparatus 1- Basket and USP Dissolution Apparatus 2- Paddle is the most
widely used apparatus among these four.
Methods: It is same as apparatus-1, a paddle replaces the basket. The tablet is allowed to sink
to the bottom of the flask before stirring. For dissolution test, U.S.P. specifies the dissolution
test medium and volume, type of apparatus to be used, 50 r.p.m. of the shaft and time limit of
the test and assay procedure. The test tolerance is expressed as a % of the labeled amount of
drug dissolved in the time limit.

Page | 26
Procedure (HCL):
The dissolution medium was maintained at 37 ± 0.50C and the basket was rotated at 50 r.p.m.
Samples (5ml) were withdrawn at timed intervals of 10minutes for 1hour and replaced with
5ml fresh dissolution medium after each sampling.
The samples were filtered and diluted appropriately before the absorbance were measured at
257 nm using ultraviolet/visible spectrophotometer (UV-1700 Pharma Spec., Simadzu
Corporation, and Japan).
One tablet was used from each brand. The content of Olmesartan HCl in each sample was
determined based on the calibration curve generated at a wavelength of 257 nm. The regression
equation for the calibration curve was, y = 0.023x - 0.009, R2 = 0.991
The dissolution profiles of the different brands of Olmesartan HCl tablets were generated from
the graph of the amount of Olmesartan HCl dissolved versus time.
Limit: The average T70 (time for 70% of the active drug to be dissolved) and the amount
dissolved at 60 minutes were obtained for each brand

Page | 27
Figure 4.5 : Automated Eight Basket Tablet Dissolution Tester (UDA-80 USP Standard,
Veego, India)
Figure 4.6: UV-VIS Spectrophotometer (UV-1700 Pharma Spec, Simadzu Corporation,

Japan)
Preparation of the standard solution: 50 mg of standard HCl was weighed accurately in a 50

ml volumetric flask. 35 ml of 0.1N HCl was added in it. It was shaked for 30 minutes and
sufficient 0.1N HCl was added to make volume up to 50ml. From this stock solution 1 ml, 2

Page | 28
ml, 3 ml, 4 ml, and 5 ml solution were taken into 100 ml volumetric flask and made up to the
mark with distilled water to obtained 10 µg/ml, 20 µg/ml, 30 µg/ml, 40 µg/ml and 50 µg/ml
concentrated respectively. Absorbance of the all solutions were measured at 248 nm by using
UV-visible spectrophotometer. The observation were recorded and graphically presented to
obtained standard curve.
Content Determination of the Samples: Content of Olmesartan can be measured by using the
following equation:
Content of Olmesartan = As ∕ A STD × W STD ∕ Ws × WA
Here,
As = Absorbance of the Sample
A std = Absorbance of the standard
W std = Weight of standard
Ws = Weight of the sample
W a = Amount of per tablet
Potency determination: Potency is the strength of a dosage form. Potency determination is the
chemical characteristics of a dosage form. The potency of official tablet is usually given in
terms of milligrams of drug per tablet and is determined by means of an official analytical
method which involves grinding several tablets in a mortar and analyzing a portion of the
resulting powder.
Method: Ten tablets were weighed accurately and ground into a fine powder. Powder
equivalent to 50 mg of Olmesartan was weighed accurately and transferred into a 100 ml
volumetric flask with 70 ml 0.1N HCl. The content was shaken for 15-20 minutes with
sonicator. Make the volume up to the mark with 0.1N HCl and filtered the solution. First 10 ml
portion of filtrate was discarded and subsequent portions were subjected to analysis. The
absorbance of collected samples were measured at 248nm nm by using UV-visible
spectrophotometer after suitable dilution (Lachman, et al., 2008).
Content of Olmesartan can be measured by using the following equation:

Page | 29
Content of Olmesartan = As ∕ Astd × Wstd ∕ Ws × Wa
Here,
 As = Absorbance of the Sample
 Astd = Absorbance of the standard
 Wstd = Weight of standard
 Ws = Weight of the sample
 Wa = Amount of per tablet
Limit: Not less than 95% and not more than 105% of the labeled amount of Olmesartan.

Page | 30
Chapter 04: Results
4.1 Weight Variation
Weight variation test is performed to check and assure that the manufactured tablets have a
uniform weight. The weight variations of ten brands of Olmesartan were determined and results
are shown in the table 4.1. All the brands complied with the specification of Pharmacopoeia.
Table No 4.1: Weight variation
Sample Weight of 10 Average Standard RSD Comment

Code Tablets(mg) (mg) deviation (%)
A1 1331.9 133.19 3.835 2.87 In Range
A2 1322.3 132.23 1.697 1.28 In Range
A3 1107.6 2.958 2.67 In Range

110.76
A4 1037.4 103.74 1.836 1.76 In Range
A5 2541.9 254.19 3.325 1.30 In Range
A6 1349.7 134.97 3.761 2.78 In Range
A7 1325.7 132.57 2.937 2.21 In Range
A8 1454.8 145.48 3.403 2.33 In Range
A9 1527.4 152.74 1.967 1.28 In Range
A10 1814.3 181.43 2.687 1.48 In Range

Page | 31
Chapter 04: Results
4.2 Friability Test
Friability means reduction of smaller pieces from a solid substance. This process evaluate the
ability of tablets to withstand abrasion, packaging, handling and shipping by subjecting them
under mechanical shock. According to BP/USP friability should not be more than 1%.
All the brands complied with the official specification.
Table 4.2: Friability Test
Sample Code Initial weight of Final weight of % of lose after Comment

10 Tablets(mg) 10 Tablets(mg) test
1331.9
A1 1331.2 0.052% In Range
1322.3
A2 1322 0.022% In Range
1107.6
A3 1107.3 0.027% In Range
1037.4
A4 1036.9 0.048% In Range
2541.9
A5 2541.1 0.031% In Range
1349.7
A6 1349 0.051% In Range
1325.7
A7 1325.3 0.030% In Range
1454.8
A8 1454.2 0.041% In Range
1527.4
A9 1526.8 0.039% In Range
1814.3
A10 1813.7 0.033% In Range

Page | 32
Chapter 04: Results
4.3 Hardness Test
Tablet hardness is the force necessary to break the tablet diametrically. It is important for drugs
that are sensitive to altered dissolution releases profiles as a function of the compressive force
employed. Hardness of all the collected samples were determined and recorded in table 4.3. 09
samples complies the official specification and other 01 didn’t.
Table 4.3 Hardness test:
Sample Average Hardness of 10 tablets Remarks

Code (kg)
A1 8.205 Comply the official specification
A8 10.178 Not comply the official specification

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Chapter 04: Results
4.4 Disintegration Time Test
Disintegration a process where oral dosage form falls apart or disintegrates in to smaller
aggregates. Availability of a drug from the dosage form depends on its ability to disintegrate
fast enough in the existing dissolution media. Results of all the samples of disintegration time
test are given in table 4.4.1, 4.4.2 & 4.4.3.And all the samples comply with official
specification.
Table 4.4.1: Disintegration Time in Water Media
Sample Code Disintegration Time Average Remarks
A1 2 min 08 sec Comply the official specification


Page | 34
Chapter 04: Results
Table 4.4.2: Disintegration Time in 0.1N HCl Media
A1 59.26 sec Comply the official specification

A4 55 sec Comply the official specification
A9 58 sec Comply the official specification
Table 4.4.3: Disintegration Time in Buffer Media


Page | 35
Chapter 04: Results
4.5 Preparation of Standard curve for Olmesartan

The solutions of Olmesartan in the concentration of 5 to 25 µg/ml were prepared. The
observations were presented in the following table 4.5.1, 4.5.2 & 4.5.3 and figure 4.5.1, 4.5.2 &
4.5.3. It was found that Bear’s- Lambert’s law was also followed in the concentration of 5 to 25
µg/ml of Olmesartan .
Table 4.5.1: Data of the Standard Curve of Olmesartan in Water media
Concentration (µg/ml) Absorbance
0 0
5 0.148
10 0.277
15 0.401
20 0.525
25 0.674

Page | 36
Chapter 04: Results
Table 4.5.2: Data of the Standard Curve of Olmesartan in 0.1N HCl media
0 0
5 0.223
10 0.468
15 0.690
20 0.965
25 1.178

Page | 37
Chapter 04: Results
Table 4.5.: Data of the Standard Curve of Olmesartan in Buffer media
0 0
5 0.438
10 0.852
15 1.355
20 1.729
25 2.201

Page | 38
Chapter 04: Results
4.6. Dissolution time test
The dissolution of ten brands of Olmesartan tablets were thoroughly analyzed in Water,0.1N
HCl (pH 1.2) & Buffer media for 60 minutes with 10 minutes intervals. All the results are
presented in table 4.6.1,4.6.2 & 4.6.3.
Table 4.6.1: Dissolution test of Collected Olmesartan Tablets in Water media
Sample % release
Code 10 min 20 min 30 min 40 min 50 min 60 min Remarks
A1 17.51% 33.83% 50.68% 68.57% 85.59% 101.3.% Satisfactory
A2 13.16% 25.45% 39.18% 58.95% 77.36% 98.9% Satisfactory
A3 11.02% 22.84% 34.42% 56.96% 79.29% 98.3% Satisfactory
A4 9.05% 25.40% 38.59% 58.37% 79.15% 98.7% Satisfactory
A5 15.13% 28.55% 46.19% 61.64% 76.41% 98.5% Satisfactory
A6 10.52% 26.62% 37.41% 53.64% 76.89% 100.4% Satisfactory
A7 14.82% 34.25% 46.24% 65.27% 81.43% 100.5% Satisfactory
A8 12.33% 28.91% 38.92% 63.97% 78.64% 99.6% Satisfactory
A9 10.87% 20.47% 42.67% 57.88% 84.25% 102.9% Satisfactory
A10 11.26% 27.61% 47.61% 64.91% 81.49% 99.2% Satisfactory

Page | 39
Chapter 04: Results
Table 4.6.2: Dissolution test of Collected Olmesartan Tablets in 0.1N HCl

media
Sample % release
A1 9.58% 31.45% 53.57% 69.42% 86.28% 98.8% Satisfactory
A2 11.90% 24.89% 38.49% 58.48% 75.77% 99.3% Satisfactory
A3 13.58% 24.55% 36.48% 59.70% 78.94% 98.7% Satisfactory
A4 11.90% 26.79% 37.22% 65.40% 77.42% 99.1% Satisfactory
A5 12.33% 27.59% 44.50% 67.88% 79.09% 100.6% Satisfactory
A6 13.51% 21.90% 36.08% 59.79% 76.88% 99.8% Satisfactory
A7 11.96% 28.39% 45.28% 66.48% 85.41% 102.7% Satisfactory
A8 13.49% 24.22% 39.60% 62.99% 79.18% 101.5% Satisfactory
A9 12.81% 22.89% 41.84% 54.89% 86.78% 99.4% Satisfactory
A10 13.56% 25.68% 46.22% 63.89% 88.90% 98.7% Satisfactory

Page | 40
Chapter 04: Results
Table 4.6.3: Dissolution test of Collected Olmesartan Tablets in Buffer media
Sample % release
A1 14.95% 36.99% 54.28% 72.14% 86.18% 99.3% Satisfactory
A2 12.19% 27.89% 44.90% 59.40% 79.48% 101.6% Satisfactory
A3 10.45% 25.79% 39.49% 57.19% 78.94% 98.6% Satisfactory
A4 16.28% 29.77% 42.66% 59.77% 78.44% 99.7% Satisfactory
A5 13.94% 27.55% 45.98% 64.90% 79.49% 100.4% Satisfactory
A6 16.22% 28.79% 42.79% 63.49% 77.90% 98.2% Satisfactory
A7 12.49% 36.58% 47.88% 66.49% 83.64% 99.6% Satisfactory
A8 14.99% 27.66% 43.65% 68.44% 81.40% 102.4% Satisfactory
A9 11.97% 25.98% 43.49% 57.88% 86.79% 98.4% Satisfactory
A10 13.79% 28.76% 45.79% 69.79% 84.23% 100.7% Satisfactory

Page | 41
Chapter 04: Results
4.7 Determination of Potency
The potency of ten brands of Olmesartan tablets was thoroughly analyzed in Water, 0.1N HCl
& Buffer media and the results are presented in table 4.7.1, 4.7.2 & 4.7.3.
Table 4.7.1: Potency of Collected Olmesartan Tablets in Water media
Sample Code Potency (%) Remarks

A1 102.2% Comply the official specification
A3 91.9% Not Comply the official specification

Page | 42
Chapter 04: Results
Table 4.7.2: Potency of Collected Olmesartan Tablets in 0.1N HCl media

Table 4.7.3: Potency of Collected Olmesartan Tablets in Buffer media


Page | 43
Chapter 5: Discussion
5.1 Weight Variation

All the samples of the study were within their shelf life at the time of investigation. All
brands showed acceptable uniformity of weight as none had percent deviation in weight
greater than 7.5% as stipulated by the USP.
5.2 Hardness and Friability

Hardness and Friability of the tablets are an essential criterion in the determination of the
ability of the tablets to resist chipping, abrasion or breakage under conditions of storage,
transportation, handling and packaging.
In this project work, hardness test results were varied from 5.382 kg to 10.178 kg. Among
the collected samples, nine brands were comply with the official specification and one
brands did not comply.
In friability test, the results of the collected brands were between 0.022% to 0.052%, which
revealed that all the samples were complies with official specification.
5.3 Disintegration Test

Disintegration is a physical process related to the mechanical breakdown of a tablet or
granulate particle into smaller particles. This review investigates disintegration
mechanisms,pharmacopoeial use of the disintegration test and scientific studies showing its
utility and potential as a pharmaceutical performance test. From this study it was found that
all brands meet the specification of disintegration time with 1 min 18 sec to 2 min 20 sec
(Water media), 58 sec to 2 min 08 sec (0.1N HCl media) & 1 min 04 sec to 2 min 40 sec
(Buffer media) of disintegration time.
5.4 Dissolution Test

Dissolution testing provides the means to evaluate critical parameters such as adequate
bioavailability and provides information necessary to formulator in development of more
efficacious and therapeutically optimal dosage forms. Dissolution analysis of
pharmaceutical dosage forms has emerged as single most important test that will ensure
quality of product. In this study, all the samples were release about 100% drug within 60
minutes, where more than 50% and more than 75% drugs were released within 40 and 50

Page | 44
Chapter 5: Discussion
minutes respectively. From these results it can be revealed that all the brands comply with
specification.
5.5 Potency Test

This test determines the strength or content of the API in the pharmaceutical tablet and is
potency test. For this test according to BP determine the amount of active ingredient by the
method described in the assay and calculate the amount of active ingredient per tablet. The
results of the ten samples lie within the range for the content of active ingredient stated in
the monograph.

Page | 45
Chapter 06: Conclusion
Conclusion
This experiment was carried out to determine the dissolution of marketed Olmesartan tablets, in
vitro dissolution,disintegration characteristics and hardness,friability of these tablets was
determined. The result found in the above studies demonstrate that the proposed UV-Visible
spectrophotometric method is simple, accurate, precise and highly sensitive. This method does
not involve any complex reagents, fixed temperature or laborious time-consuming sample
preparation. Therefore, it can be used for the determination of Olmesartan either in bulk or in
their corresponding dosage forms without interference from commonly used excipients and
related substances.
It is found that the potency of Olmesartan tablet is within the BP and USP and dissolution is
relevant with the potency but the hardness of one sample was not comply with the BP and USP
specification. But, the release of drug within time was perfect. All of them comply with the
range of BP, USP and other formularies. Further study if required to improve the research
work.
I did my experiment with Ten-branded Olmesartan drug, but if I got a chance to work with a
vast spectrum of Olmesartan drugs for long time then the result will be more comprehensive.

Page | 46
Chapter 07: Reference
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Comparative Study of Different Brands of

Olmesartan Tablets Available in Bangladesh

A dissertation submitted to the Department of Pharmacy,

Submission Date: September,2022

SI no. Topic Page No.

1.8.2 Shelf life 14

Comparative Study of Different Brands of Olmesartan Tablets Available in Bangladesh

Chapter-02: Design of Investigation

Chapter-03: Materials and Methods

SI no. Topic Page No.

3.2 Equipments Used 21

Comparative Study of Different Brands of Olmesartan Tablets Available in Bangladesh

Comparative Study of Different Brands of Olmesartan Tablets Available in Bangladesh

Comparative Study of Different Brands of Olmesartan Tablets Available in Bangladesh

Molar mass: 558.6g/mol

Comparative Study of Different Brands of Olmesartan Available in Bangladesh Tablets

Olmesartan also effects on the renin-angiotensin aldosterone system (RAAS) plays

Comparative Study of Different Brands of Olmesartan Available in Bangladesh Tablets

Comparative Study of Different Brands of Olmesartan Available in Bangladesh Tablets

 Tabulated list of adverse reactions

Table of adverse reaction:

Blood and lymphatic Thrombocytopenia Uncommon

Immune system Anaphylactic reaction Uncommon

Metabolism and Hypertriglyceridaemia Common

Nervous system Dizziness Common

Ear and labyrinth Vertigo Uncommon

Cardiac disorders Angina pectoris Uncommon

Vascular disorders Hypotension Rare

Respiratory, thoracic and Bronchitis Common

Comparative Study of Different Brands of Olmesartan Available in Bangladesh Tablets

Gastrointestinal Gastroenteritis Common

Abdominal pain Common

Sprue-like enteropathy (see Very rare

Hepatobiliary disorders Autoimmune hepatitis* Not known

Skin and subcutaneous Exanthema Uncommon

Musculoskeletal and Arthritis Common

Skeletal pain Common

Muscle spasm Rare

Renal and urinary Haematuria Common

Acute renal failure Rare

Comparative Study of Different Brands of Olmesartan Available in Bangladesh Tablets

Renal insufficiency Rare

General disorders and Pain Common

Peripheral oedema Common

Influenza-like symptoms Common

Face oedema Uncommon

Investigations Hepatic enzymes increased Common

Blood urea increased Common

Blood creatine phosphokinase Common

Comparative Study of Different Brands of Olmesartan Available in Bangladesh Tablets

Olmesartan belongs to the angiotensin II receptor blocker (ARB) family of drugs,

Olmesartan also affects the renin-angiotensin aldosterone system (RAAS), which

By comparison, the angiotensin-converting enzyme inhibitor (ACEi) class of

Olmesartan is commonly used for the management of hypertension and Type 2

Comparative Study of Different Brands of Olmesartan Available in Bangladesh Tablets

Orally available olmesartan is produced as the prodrug olmesartan medoxomil

1.4 Medical uses: