Instruction to write Introduction

1. Introduction:
Type 2 diabetes (In short)
Drugs used in type 2 diabetes (In short)
1.1 Aim & Objective of the study:
1.2 Type 2 diabetes (Details)
1.3 Treatment
1.4 Dosage form
1.5 Quality control tests for tablet
1.6 Excipients
1.7 Literature review on some recent researches
1.8 Drug profile
1.8.1 Physicochemical properties of gliclazide
1.8.2 Indication
1.8.3 Cautions
1.8.4 Contraindications
1.8.5 Dose
1.8.6 Pharmacokinetics
1.8.7 Mechanism of Action
1.8.8 Side effects & adverse effects
1.8.9 Drug interaction
1.8.10 Some available brands in Bangladesh
1.8.11 Pregnancy profile
1. Introduction:
Hypertension (HTN), one of the most common medical disorders, is associated with an increased
incidence of all-cause and cardiovascular disease (CVD) mortality [Pescatelloet al., 2004]. Hypertension
refers to the chronic condition in which the blood pressure in the arteries is elevated above 140/90 mmHg
[Kaur et al., 2013]. Usually the symptoms and findings are: headache, dizziness, nausea or vomiting,
disturbed vision, irritability, hyperactivity, facial nerve palsy, convulsions, changes in state of
consciousness, personality change, anxiety, tachycardia, and episodes of sweating, dyspnea, polyuria,
polydipsia, weakness, and weight loss. Headaches may have been a complaint for a long time, and when
severe are associated with nausea and vomiting. Failing vision, even blindness, and dizziness are not
unusual. The clinical picture may suggest a disorder of the nervous system because of such symptoms as
lethargy, coma, seizures, delirium, and facial palsy. Other symptoms may be due to the long-term effects
of hypertension on target organs (congestive heart failure, impaired renal function, and stroke). However,
some symptoms are related to specific causes of hypertension. Thus palpitations and sweating are
characteristic of pheochromocytoma, and obesity, weakness, and ecchymosis are associated with
Cushing's syndrome. This variety of symptoms, mainly nonspecific, illustrates why measurement of blood
pressure should be part of the physical examination of the young as well as adults. When blood pressures
are not determined, hypertension is not discovered until late in the course of the illness [Londe, 1978].

1.1Aim and Objective of the Study:

Losartan potassium is an orally active, nonpeptide angiotensin II (AII) receptor antagonist. The motive of
this study was to collate and analyze the quality parameters of three different commercially available
brands of Losartan Potassium 25mg tablet using in vitro laboratory tests. Information obtained from such
studies can be used to maximize the safety of local people.

1.2 Hypertension:
The goal of antihypertensive therapy is to abolish the risks associated with blood pressure (BP) elevation
without adversely affecting quality of life. Epidemiologic studies and clinical trials have been used to
define individual risk and set appropriate BP targets [Chobanianet al., 2003], recognizing that these
targets reflect expert consensus based on available data and are subject to revision as additional evidence
is obtained [Mancia, 2009]. Drug selection is based on efficacy in lowering BP and in reducing
cardiovascular (CV) end points including stroke, myocardial infarction, and heart failure. Although the
choice of initial drug therapy exerts some effect on long-term outcomes, it is evident that BP reduction
per se is the primary determinant of CV risk reduction. As a result, there has been a progressive lowering
of BP targets in large segments of the hypertensive population, including diabetics and patients with
established renal or vascular disease [Williams, 2004; Rosendorff, 2007]. Hypertension is also an
increasing problem in Southeast Asia, particularly in Bangladesh. The overall prevalence of hypertension
was 26.4 %, and the prevalence was higher in women (32.4 %) than men (20.3 %) [Chowdhury et al.,
2016].
Risk Factors of Hypertension: Certain factors can increase the risk of developing hypertension; these
are listed as follows [Giles et al., 2009]:

 Increasing age
 Elevated blood pressure
 High heart rate
  Overweight ⁄ obesity
 Increased body mass index
 Increased abdominal circumference
 Increased abdominal adiposity (waist-to-hip ratio)
 Dyslipidemia
 Elevated LDL or non-HDL cholesterol
 Low HDL cholesterol
 Elevated triglycerides
 Elevated blood glucose, insulin resistance, or diabetes
 Chronic kidney disease
 Smoking
 Family history of premature CVD
 Sedentary lifestyle
 Psychosocial stress

1.3 Treatment of Hypertension:

Management of hypertension is essential for which antihypertensive drugs are used. Management aims to
control arterial pressure, prevent end-organ damage (cerebrovascular, cardiovascular, and renal) and
reduce the risk of premature death [Jackson and Bellamy, 2015].Use of antihypertensive agents, alone or
in combination, can lower blood pressure with minimal risk of serious toxicity in most patients.
Losartan Potassium as an Antihypertensive: Losartan Potassium is one of the safest, effective drugs
used widely in the treatment of hypertension. In 511 ambulatory patients with mild to moderate
hypertension, losartan 50 mg once a day lowered blood pressure over 24 h with a favorable
peak[Tsunoda, 1993]. Losartan/ HCTZ, alone or as part of a regimen with other standard antihypertensive
agents, is effective and well tolerated in the treatment of patients with severe hypertension [Oparil. 2001].
The drug is widely used as an antihypertensive agent so we have chosen the drug for evaluating.

1.4 Dosage Form:

Drugs are rarely administered as pure chemical substances alone and are almost always given as
formulated preparations or medicines. These can vary from relatively simple solutions to complex drug
delivery systems through the use of appropriate additives or excipients in the formulations. The excipients
provide varied and specialized pharmaceutical functions. It is the formulation additives that, among other
things, solubilize, suspend, thicken, preserve, emulsify, modify dissolution, improve the compressibility
and flavor drug substances to form various preparations or dosage forms. The principal objective of
dosage form design is to achieve a predictable therapeutic response to a drug included in a formulation
which is capable of large-scale manufacture with reproducible product quality. Different dosage forms are
given below in Table 1 [York, 1988]:
Table1: Dosage Forms Available for Different Administration Routes
 Route Dosage Form
Oral Solutions, syrups, suspensions, emulsions, powders, granules, capsules, tablets
Rectal Suppositories, ointments, creams, solutions
Topical Ointments, creams, pastes, lotions, gels, solutions, topical aerosols
Parenteral Injections (solution, suspension, emulsion), implants, dialysis solutions
Respirator Aerosols (Solution, suspension, emulsion, powder), inhalations, sprays, gases
y
Nasal Solutions, inhalations
Eye Solutions, ointments, creams
Ear Solutions, suspensions, ointments, creams
Several specialized transport mechanisms are postulated, including active and facilitated transport. Once
absorbed, the drug can exert a therapeutic effect eithers locally or at a site of action remote from that of
administration. In the latter case the drug has to be transported in body fluids (Figure: 1) [York,1988].

Figure1: Pathways that Drug May Take Following the Administration of a Dosage Form by Different
Route
Tablet Dosage Form: Tablets are solid dosage forms manufactured either by dry granulation, wet
granulation or direct compression containing medicaments with or without excipients, intended to
produce desired pharmacological response [Nagashree et al., 2015]. Tablets have better patient
acceptance and compliance and may offer improved biopharmaceutical properties, improved efficacy, and
better safety compared with conventional oral dosage forms. Today, tablets dosage forms are most
convenient and widely used dosage forms [Hirani et al., 2009]. That’s why tablets dosage form has been
chosen.

1.5 Quality Control Test for Tablet:

Quality control tests are important to ensure that they are consistent, safe, effective and predictable.
Health issues are related to these kind of products so they has to be pure and in accurate form. In
pharmaceutical industries quality control inspectors are responsible for doing these tests. The following
test are done to evaluate the quality parameters:
Weight Variation- It is performed to check the uniformity of the tablet and to ensure the weight variation
complies with USP specification [Reddy et al., 2014].
Thickness Test - Thickness of tablet is measured by Venire caliper/screw gauge. The thickness of the
tablet related to the tablet hardness and can be used an initial control parameter. Thickness must be
controlled to facilitate [Reddy et al., 2014].
Diameter Test- Tablet diameter is also an important test. Screw gauge and caliper are used [Reddy et al.,
2014].
Hardness- It is the load required to crush the tablet when placed on its edge. The test is performed to
meet the need for pressure adjustments on the tablet manufacturing machine [Ahmed et al., 2012].
Friability Test-It refers to the ability of the compressed tablet to avoid fracture and breaking during
transport. Friability is defined as the % of weight loss by tablets due to mechanical action during the test
[Ahmed et al., 2012].
Potency- Analysis of drug potency in tablets is to evaluate the tablets potential for efficacy by monitoring
the presence of drug in dosage form and also requisite for the establishment of stability data [Haque et al.,
2017].
Dissolution Test-Dissolution is an official test. It is performed to check the percentage release from the
dosage forms. Dissolution is considered one of the most important quality control tests performed on
pharmaceutical dosage forms and is now developing into a tool for predicting bioavailability, and in some
cases, replacing clinical studies to determine bioequivalence. Dissolution behavior of drugs has a
significant effect on their pharmacological activity. In fact, a direct relationship between in vitro
dissolution rate of many drugs and their bioavailability has been demonstrated and is generally referred to
as in vitro-in vivo correlation [Mathur et al., 2015].
Disintegration Test-This is the official test which testifies the time required for a tablet to disintegrate in
the solution. Disintegration test helps in knowing the API solubility in the gastric fluids of the digestive
system. Temperatures are maintained accordingly for each tablet. It is calculated by the time required to
dissolve the tablet in the liquid and compared with the standard time in the pharmacopoeia [Mohammad,
2016].

1.6Excipients:
An excipient interacts with the active in the formulated dosage form and/or provides a matrix that can
affect critical quality attributes of the drug substance, including stability and bioavailability. Some type of
excipients that are used in tablet formulation:

 Antiadherents: Antiadherents reduce the adhesion between the powder (granules) and the
punch faces and thus prevent sticking to tablet punches by offering a non-stick surface.
E.g. Magnesium Stearate.
 Binders: Binders hold the ingredients in a tablet together. Binders ensure that tablets and
granules can be formed with required mechanical strength, and give volume to low active
dose tablets. E.g. Sucrose, lactose.
 Coating materials: Tablet coatings protect tablet ingredients from deterioration by
moisture in the air and make large or unpleasant-tasting tablets easier to swallow. E.g.
Hydroxypropyl methylcellulose (HPMC). Enteric control the rate of drug release and
determine where the drug will be released in the digestive tract. Materials used for enteric
coatings include fatty acids, waxes, shellac, plastics, and plant fibers.
 Colors: Colors are added to improve the appearance of a formulation. Color consistency
is important as it allows easy identification of a medication. E.g. Titanium oxide.
 Disintegrants: Disintegrants expand and dissolve when wet causing the tablet to break
apart in the digestive tract, or in specific segments of the digestion process, releasing the
active ingredients for absorption. E.g.Cross-linked polyvinylpyrrolidone, cross-linked
sodium carboxymethyl cellulose (croscarmellose sodium).
 Glidants: Glidants are used to promote powder flow by reducing inter-particle friction
and cohesion. E.g. Silica gel, fumed silica, talc, and magnesium carbonate.
 Lubricants: Lubricants prevent ingredients from clumping together and from sticking to
the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation
and ejection can occur with low friction between the solid and die wall. E.g. Talc, silica.
1.7 Literature Review on Some Recent Researches:
1. Antiproteinuric effects of enalapril and losartan: a pilot study by White, C.T. et al. in
2010.The aim was to compare the antiproteinuric effects of enalapril and losartan in six
children with proteinuria and underlying renal injury.In the losartan group, the protein
reduction achieved was 31%, with a range of 14%–52%. There did not appear to be any
difference in percentage reduction based on order of the drugs received. Only patient 5
achieved a reduction in proteinuria into the normal range of 0–4 mg/m2 per hour.
 2. Effect of losartan, an angiotensin ii receptor antagonist, on portal pressure in cirrhosis by
Schneider A.W. et al.in 2003.The study was done to determine the antihypertensive
effects of losartan on portal pressure with particular attention paid to potential side effects.
Losartan in an oral dose of 25 mg once daily has an exceptionally pronounced portal
pressure–lowering effect in portal hypertension and is well tolerated. Long-term studies
are needed to evaluate the effects of losartan treatment on the incidence of variceal
bleeding and the prognosis of patients with cirrhosis.
3. Clinical pharmacokinetics of losartan by Sica, D.A., Gehr, T.W.B., Ghosh, S. in 2005.The
aim was to find the clinical pharmacokinetics of Losartan.The study has been sufficiently
positive to support a more widespread use of angiotensin-receptor antagonists in the
setting of various end-organ diseases. Losartan, like other angiotensin-receptor
antagonists, is devoid of significant adverse effects.
4. Comparative pharmacokinetics of two tablet formulations of losartan: bioequivalence
assessment by Tamimi, J.J.I. et al. in 2005. The aim of this study was to determine the
bioequivalence of a new tablet formulation of losartan produced locally and the result
showed that both products can be considered equally effective and safe in medical
practice.
5. Pharmacokinetics and bioequivalence evaluation of two losartan potassium 50 mg tablets:
a single-dose, randomized-sequence, open-label, two-way crossover study in healthy
Chinese male volunteers by Jia, J.et al.in 2010.The aim was to meet the requirements for
marketing a new generic product, the study was designed to compare the pharmacokinetic
parameters and relative bioavailability of a new generic losartan potassium 50-mg tablet
(test formulation) with a branded 50-mg tab- let (reference formulation) in healthy
Chinese male volunteers. The result showed that thetablets met the regulatory criteria for
assuming bioequivalence to the established reference formulation. Both formulations were
well tolerated.

1.8 Drug Profile:

1.8.1 Physicochemical Properties of Losartan Potassium:
Losartan potassium, the first of a new class of antihypertensive agents, is an angiotensin II receptor (type
AT1) antagonist which is chemically described as 2-butyl-4-chloro-1-[p-(o-1Htetrazol-5-
ylphenyl)benzyl]imidazole-5-methanol mono potassium salt [Tamimi et al., 2005].
Structure: Structural formula of losartan potassium as well as its active metabolite is given below in
Figure 2 [Goa and Wagstaff, 1996]:

Figure 2: Structural Formulae of Losartan Potassium and its Active Metabolite E3174
Some physicochemical characteristics of Losartan potassium is given below [Keerthi and Takkellapati,
2012]:
Molecular formula: C22H23ClKN6O
Molecular weight: 422.91
PKa: 14.27
Description: White to off-white free-flowing crystalline powder.
Solubility: Freely soluble in methanol, ethanol, and water insoluble in Chloroform.
Storage condition: The storage condition recommends to store in tight containers.
Melting point: 184 °C
BCS Classification: Losartan Potassium is class III drug (High Solubility & low Permeability)
Metabolite: Oxidation of the 5-hydroxymethyl group on the Imidazole ring results in the active metabolite
of Losartan.

1.8.2 Indication:
Losartan is used to treat high blood pressure (hypertension) and to help protect the kidneys from damage
due to diabetes. It is also used to lower the risk of strokes in patients with high blood pressure and an
enlarged heart. They are useful alternatives for patients who have to discontinue an ACE inhibitor
because of persistent cough.

1.8.3 Cautions:
They are to be used with caution in renal artery stenosis. It is advised that plasma-potassium
concentration be monitored in the elderly and in patients with renal insufficiency; lower initial doses may
be suitable in these patients [Khan, 2015].

1.8.4 Contraindications:
Losartan potassium should be avoided in pregnancy and bilateral renal artery stenosis.

1.8.5 Dose:
Usually 50mg once daily (Elderly over 75 years, moderate to severe renal impairment, intravascular
volume depletion, initially 25 mg once daily); if necessary increase after several weeks to 100 mg once
daily [Khan, 2015].
Available dosage forms:Tablet dosage form (25mg, 50mg, 100mg).

1.8.6 Pharmacokinetics:
Losartan undergoes first-pass metabolism in the liver via the CYP system to form its active metabolite
EXP3174, which is 10–40 times more potent than losartan when given intravenously. Although food
delays its absorption and reduces its maximum plasma concentration (Cmax), this is not clinically
significant [Israili, 2000]. Its dose must be decreased by half in patients with severe hepatic impairment.
Any CYP2C9 enzyme inhibitors or inducers may reduce the effectiveness of losartan, and this must be
considered during drug selection [Song and White, 2000].
Absorption, metabolism of losartan potassium are given below in details [Sica et al., 2005]:
Absorption: Following oral administration, Losartan is well absorbed and undergoes substantial first-
pass metabolism; the systemic bioavailability ofLosartan is approximately 33%. About 14% of an orally
administered dose of Losartan is converted to the active metabolite.
Metabolism: Losartan is the first orally available angiotensin-receptor antagonist without agonist
properties. Following oral administration, losartan is rapidly absorbed, reaching maximum concentrations
1–2 hours post-administration. After oral administration approximately 14% of a losartan dose is
converted to the pharmacologically active E 3174 metabolite. E 3174 is 10- to 40-fold more potent than
its parent compound and its estimated terminal half-life ranges from 6 to 9 hours. The pharmacokinetics
of losartan and E 3174 are linear, dose-proportional and do not substantially change with repetitive
administration. The recommended dosage of losartan 50 mg/day can be administered without regard to
food. There are no clinically significant effects of age, sex or race on the pharmacokinetics of losartan,
and no dosage adjustment is necessary in patients with mild hepatic impairment or various degrees of
renal insufficiency. Losartan, or its E 3174 metabolite, is not removed during hemodialysis. The major
metabolic pathway for losartan is by the cytochrome P450 (CYP) 3A4, 2C9 and 2C10 isoenzymes.
Overall, losartan has a favorable drug-drug interaction profile, as evidenced by the lack of clinically
relevant interactions between this drug and a range of inhibitors and stimulators of the CYP450 system.
Losartan does not have a drug-drug interaction with hydrochlorothiazide, warfarin or digoxin. Losartan
should be avoided in pregnancy, as is the case with all other angiotensin-receptor antagonists. When
given in the second and third trimester of pregnancy, losartan is often associated with serious fetal
toxicity. Losartan is a competitive antagonist that causes a parallel rightward shift of the concentration-
contractile response curve to angiotensin-II, while E 3174 is a noncompetitive ‘insurmountable’
antagonist of angiotensin-II.
Some other pharmacodynamics characteristics of losartan potassium are given below [Lo et al., 1995]:
Half-life of losartan potassium: 2.1 hours
Half-life of EXP3174: 6.3 hours
Peak plasma concentration of losartan potassium: 1 hour
Peak plasma concentration of EXP3174: 3 1/2 hours
Blood brain barrier: Can’t cross [Bui, 1992]
Volume of distribution of losartan potassium: 34 Liter
Volume of distribution of EXP3174: 10 L
Bioavailability of losartan potassium: 33%
Tmax of losartan potassium: 1-1.5 hours
Protein binding for losartan potassium: 98% [Keerthi and Takkellapati, 2012].
Renal clearance of losartan potassium: 70 ml/min for 12% of plasma clearance.
Renal clearance of EXP3174: 26 ml/min, which accounted for 55% of plasma clearance
Main metabolic organ of losartan potassium: Liver
Average plasma clearance of losartan potassium: 610 ml/min
Average plasma clearance of EXP3174: 47 ml/min
The area under the plasma concentration-time curve of EXP3174 was about four times that of losartan
potassium. The low bioavailability was mainly attributable to first-pass metabolism. After intravenous or
oral administration of losartan the conversion of losartan to the metabolite EXP3174 is 14%.

1.8.7 Mechanism of Action:

Angiotensin-receptor blockers are a specific new class of non-peptide angiotensin II receptor antagonists.
They work by blocking A1 receptors at the tissue level. Several factors, including the level of angiotensin
II and the number of AT1 receptors available, influence the action of AT1receptor blockers. The number
of AT1 receptors on the cell surface determines the magnitude of the blockers' effect. This has been
demonstrated under conditions (E.g. sodium depletion) that increase numbers of angiotensin receptors
and are associated with increased response to ARBs. By binding to AT1 receptors, an ARB decreases
aldosterone, vasopressin, and catecholamine release. In addition to decreasing sympathetic outflow,
AT1receptor blockade causes vascular vasodilation and inhibition of sodium and water reabsorption in the
kidney. Collectively, these effects lead to a reduction in blood pressure. Similarly, ARBs may benefit the
heart through anti-inotropic and ant proliferative effects. The AT 1 receptor is present in juxtaglomerular
cells, where it regulates renin secretion. Inhibition of AT1 receptor is associated with an increase in renin
secretion that leads to more angiotensin II generation. The increase in angiotensin II after AT 1-receptor
blockade allows stimulation of the AT2 receptor [Siragy and Bedigian, 1999].
The mechanism of action of losartan potassium is illustrated in the Figure 2 below[Ashraf et al., 2015]:
 Figure3: Mechanism of Action of Losartan Potassium (ARB)

1.8.8 Side Effects and Adverse Effects:

There is no major/serious side effects noticed after taking losartan potassium in perfect dose. The most
common side effects are cough, dizziness, headache, nausea, diarrhea, taste disturbance, myalgia,
migraine, urticarial, pruritus, rash, altered liver function [Khan S.I., 2015].
The most common adverse effects for losartan in adults are upper respiratory infections, dizziness, and
back pain. Losartan should not be taken by people who are diabetic and taking aliskiren. Anemia may
occur, due to inhibition of the renin–angiotensin system. As with other angiotensin receptor blockers,
losartan may injure the liver, although this effect appears to be rare. Electrolyte imbalances may occur in
people taking losartan with kidney problems. Adverse outcomes do not differ by gender, age
[Cheungpasitporn et al., 2015]. Post marketing surveillance has shown that angioedema, a rare but life-
threatening adverse effect of ACE inhibitors, also occurs with losartan potassium. Further data are needed
on the use of losartan potassium in patients with renal impairment before accepting the recommendation
that dosage adjustment is not necessary. The pharmacokinetics and pharmacodynamics of losartan
potassium in patients with hepatic disease also require further investigation.Losartan potassium increases
uric acid secretion and lowers plasma uric acid levels, which may be of benefit when losartan potassium
is combined with a thiazide diuretic, but which may otherwise lead to uric acid stone formation and
possibly to nephropathy.Simple control of blood pressure is no longer an adequate goal in the
management of hypertension. Any new antihypertensive agent should also reduce cardiovascular events,
prevent or cause regression of end-organ damage such as left ventricular hypertrophy, atherosclerosis and
renal failure, and should not impair quality of life. Such data on losartan potassium are not currently
available [Burrell, 1997].
1.8.9 Drug Interaction:
Fluconazole: Fluconazole interacts with losartan and results in the suppression of its conversion to the
active metabolite E-3174.Studies in healthy volunteers have shown that the mean peak plasma
concentration (Cmax) and area under the concentration-time curve (AUC) of losartan were elevated,
when losartan was co-administered with fluconazole [Kaukonen et al., 1998].
Phenobarbital: When phenobarbital was co-administered with losartan to healthy volunteers, significant
reductions in plasma concentrations of losartan observed [Goldberg et al., 1996].
Fluvastatin: The oral clearance of losartan is reduced by about 20% when the potassium salt is co-
administered with fluvastatin, although this effect has not been shown to be of clinical significance
[Scripture and Pieper, 2001].
Rifampicin and Erythromycin: Hypothetically, there is a possibility of interactions between losartan
and several different classes of antibacterial agents, Rifampicin (rifampin). By contrast, erythromycin, do
not have any significant effect on the AUC or half-life of losartan potassium [Williamson et al., 1998].
Indomethacin: Con-current administration of indomethacin significantly attenuated the 24-hour
ambulatory diastolic blood pressure response to losartan in hypertensive patients [Conlin et al., 2000].
Aspirin: Aspirin (acetylsalicylic acid) exerted no marked effect on blood pressure control in patients with
essential hypertension receiving losartan potassium [Nawarskas et al., 1999].
Cimetidine: In the case of concurrent administration of losartan and cimetidine, an 18% increase in the
bioavailability of cimetidine is observed [Schaefer and Porter, 1996].
Digoxin and Warfarin: There is no pharmacokinetic evidence of clinically significant interactions
between digoxin or warfarin and losartan potassium [Kong et al., 1995; Goldberg et al., 1996].
Hydrochlorothiazide: Observations in hypertensive patients suggest that there is no clinically significant
effect of hydrochlorothiazide on the pharmacokinetics of losartan or E-3174 [McCrea et al., 1995].

1.8.10 Impurities:
In the therapy of hypertension, losartan is the first non-peptide drug that inhibits the renin-angiotensin
system by selectively blocking the interaction of angiotensin II with its receptor. Losartan potassium
binds selectively, competitively and with high affinity to the subtype 1 receptor (AT1) receptor, thereby
blocking angiotensin II –induced physiological effects [Bui et al., 1992]. According to European
pharmacopoeia 7.0, there are elven related impurities and degradation products of losartan, including
impurity B, impurity C, impurity D, impurity E, impurity F, impurity I, impurity G and degradation
products J, K, L and M. Among them, degradation products M and L formed under thermal and acidic
conditions, are two dimers of losartan. Process impurity C is isomers of losartan. In addition, these
impurities are introduced by the synthesis process including impurity B, D, E, F, I and G. Finally,
degradation product K is the oxidation product of losartan and degradation product J is the alkaline
degradation product. The Figure 4 shows the chemical structures of losartan potassium and its eleven
impurities and degradation products B, C, D, E, F, J, I, G, K, L and M.
.

Figure4: The Chemical Structures of Losartan Potassium and Its Eleven Impurities and Degradation
Products B, C, D, E, F, J, I, G, K, L and M.
The assessment of these related impurities and degradation products is one of the key considerations in
process preparation studies. And they must be eliminated in downstream process steps or minimized to
fulfill the requirements of limitation in the final drug substance [European Pharmacopoeia Commission,
2009].The gradient reversed-phase HPLC method for the simultaneous quantitative determination of
losartan potassium and its eleven related impurities and degradation products in a tablet formulation is
validated to be simple, sensitive, precise, reliable and robust. The validated method can be available for
routine analysis and quality control of losartan potassium and its eleven impurities in the tablet
formulation of the process of production [Qiu et al., 2015].

1.8.11 Some Available Brands in Bangladesh: Ten available brands of losartan potassium
from top listed pharmaceutical companies in Bangladesh are given below as well as their available dose
[Khan, 2015].
Table 2: Some Available Brands in Bangladesh with Dose and Manufacturer Name

Serial No. Company Name Brand Name 25mg 50mg 100mg

1 Square Pharmaceuticals Ltd. Angiloc   
2 Incepta Pharmaceuticals Osartil   
3 Beximco Pharmaceuticals Prosan   -
4 Opsonin Pharmaceuticals Larb   
5 Renata Pharmaceuticals Ostan   -
6 Eskayef Pharmaceuticals Ltd. Cardon   -
7 ACME Pharmaceuticals Losart -  -
8 Aristopharma Ltd. Osartan   -
9 Drug international Ltd. Losardil   
10 Healthcare Pharmaceutical Losacor -  -