Int. J. Pharm. Sci. Rev. Res., 35(2), November – December 2015; Art icle No.

31, Pages: 168-172 ISSN 0976 – 044X

Research Article

Comparative in-vitro Bioavailability Studies on Different Brands of Losartan Potassium Tablet

and its Pharmacoeconomics Study
1 1 1 1 1 2 1 1
M uhamm ad Amer* , Shazma M arryam , Asif M ehmood Aslam , Tahir Aqeel , R.Z Saeed-Ul-Haq , Saeed Ur Rashid Nazir , Anum Zulfiqar , Israr Ali Khan
1
Depart ment of Phar macy, The Universit y of Lahore, Islamabad Campus, Islamabad, Pakist an.
2
Facult y of Pharmacy, Universit y of Sargodha, Sargodha, Pakist an.
* Corresponding author’s E-mail: amerpharm@yahoo.com

Accepted on: 27-10-2015; Finalized on: 30-11-2015.

ABSTRACT

Losart an pot assium is a non-pept ide angiot ensin II recept or antagonist used in the t reat ment of hypert ension. It exhibit s highly
variable and low oral bioavailabilit y approximately 33%. Losart an is, therefore, considered a class III in the Bio-pharmaceut ics
Classificat ion Syst em, because it has high solubilit y and low permeabilit y. The object ive of this study was t o evaluat e t he suit able
brand of Losart an pot assium t ablet having bet ter dissolut ion profile, t o evaluat e study of physicochemical equivalence of different
brands as well as t o det ermine t hat which brand is economically as well as t herapeut ically effect ive for the patient of hypertension.
Six brands (five national and one multinat ional brand) of Losart an pot assium 50mg w ere collect ed randomly from different
pharmacies. Six select ed brands were coded as F1, F2, F3, F4, F5 and F6. The different brands were evaluat ed for hardness, friabilit y,
weight variat ion, disintegration, chemical assay and dissolut ion test s. Different brands were found wit hin in t he limit s for friabilit y
and disint egration t ime tests. All t he coat ed t ablet s passed t he weight variation t est as t he percent age of weight variat ion was
wit hin USP limit s of ± 7.5% of t he average weight . The chemical assay t est of all the t ablet s showed t hat none had pot ency less than
t he required specificat ions of USP. In comparison, F5 and F6 brands showed bett er results in t erms of compliance wit h USP result s
limit s for different physico-chemical t est s. The results of all t he test s performed show that GM P and cGM P guidelines have been
followed during manufact uring. This st udy proved the physicochemical equivalent of t he six different brands. So if one brand is not
available in t he market t hen any of t he ot her t hree brands can be taken in place of t hat unavailable brand according t o t he economic
condit ions of the patient s.

Keywords: Losart an pot assium, In-Vit ro Dissolution, Disint egration Time, Physicochemical Equivalency.

INTRODUCTION AT1 recept or blockade result s in an increase in plasm a

renin activit y (PRA) follow ed by increases in plasm a

H
ypert ension is t he m ost comm on cardiovascular
angiot ensin II concentrat ion.
disease. The prevalence of hypert ension increases
w it h advancing age; for exam ple, about 50% of Peak plasm a levels of losart an and EXP 3174 occur
people bet ween t he ages of 60 and 69 years old have approxim at ely 1 t o 3 hours after oral adm inist rat ion,
hypert ension, and t he prevalence is furt her increased respectively, and t he plasm a half-lives are 2.5 and 6 t o 9
beyond age 70. hours, respectively. Bot h losart an and it s active
m et abolit e are ≥ 99% bound to plasma proteins, primarily
Elevat ed art erial pressure causes pat hological changes in
albumin. The volum e of distribution of losart an is 34
t he vasculat ure and hypertrophy of the left ventricle. As a
lit ers. Approxim ately 14% of an oral dose of losart an is
consequence, hypert ension is the principal cause of
convert ed t o t he 5-carboxylic acid m et abolit e EXP 3174,
st roke, is a m ajor risk fact or for coronary art ery disease
w hich is m ore pot ent t han losart an as an AT1-recept or
and it s at t endant com plicat ions m yocardial infarct ion and
ant agonist . The m et abolism of losart an t o EXP 3174 and
sudden cardiac deat h, and is a m ajor contribut or t o
t o inact ive m et abolit es is m ediat ed by CYP2C9 and
cardiac failure, renal insufficiency, and dissecting
CYP3A4. The plasm a clearances of losart an and EXP 3174
aneurysm of t he aort a. Hypertension is defined as a
(600 and 50 m l/ min, respectively) are due t o renal
sust ained increase in blood pressure ≥140/90 mm Hg, a
clearance (75 and 25 ml/ min, respectively) and hepatic
criterion w here t he risk of hypert ension-relat ed
clearance (m et abolism and biliary excretion). The plasm a
cardiovascular disease is high enough t o m erit m edical
1 clearance of losart an and EXP 3174 is affected by hepatic
at t ent ion . 9
but not renal insufficiency .
Losart an is a non-pept ide angiotensin II recept or
The usual daily dose given orally in children ≥6 years of
ant agonist w it h high affinit y and selectivit y for the AT1
2-7 age initially, 0.7 m g/ kg (up t o 50mg) once daily (m axim um
recept or . Losart an blocks t he vasoconst rict or and
dosage of 1.4 m g/ kg or 100 m g daily). In adult s initially,
aldost erone-secret ing effect s of angiot ensin II by
50m g once daily in adult s w it hout int ravascular volum e
inhibit ing t he binding of angiot ensin II t o t he AT1
2,5,8 depletion. In adult s wit h depletion of intravascular
recept or .
volume, t he usual initial dosage is 25 mg once daily. 25–
100m g daily, given in 1 dose or 2 divided doses; no
addit ional t herapeut ic benefit wit h higher dosages. If

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Int. J. Pharm. Sci. Rev. Res., 35(2), November – December 2015; Art icle No. 31, Pages: 168-172
effect iveness diminishes t ow ard t he end of t he dosing
int erval in pat ient s t reat ed once daily, consider increasing
dosage or adm inist ering drug in 2 divided doses.
10,11
M axim um 1.4 m g/ kg or 100 m g daily .
The dissolut ion profile of all select ed brands is in t he
range of st andard lim it s so aft er it s pharm acoeconom ics
evaluation it is recomm ended t hat anyone of t he select ed
brands can use according t o t he financial st at us of t he
pat ient s. All brands are t herapeut ically equivalent so
pat ient s can use any brand alt ernat ively according t o his
econom ic conditions. How ever, out of t hese six brands F5
show ed bet t er dissolut ion profile and is com parat ively of
low cost .
This st udy w as aim ed t o com pare t he in vit ro equivalence
of comm only prescribed brands of losart an pot assium in
Pakist an and t o help healt hcare providers select t he m ost
econom ical brand of losart an pot assium having bet t er in
vit ro perform ance.
M ATERIALS AND M ETHODS
Chemical
The st andard Losart an pot assium pow der w as gift ed by
Pearl Pharm aceut ical Islam abad, Pakist an. Distilled w ater
used for dilution w as of analyt ical reagent grade.
Sampling
To st udy t he in vit ro drug release five national and one
m ultinat ional brands of losart an pot assium w ere
collect ed randomly from different pharm acies. The
sam ples were checked for their bat ch num ber,
m anufact uring and expiry dat es, pack size and price per
pack. These sam ples were random ly coded as F1, F2, F3,
F4, F5, and F6 t he reference brand and st ored properly.
All t he collected sam ples have labeled act ive ingredient
Losart an pot assium 50mg and w ere packaged in blist er
packing.
Tests of Physicochemical Parameter
Hardness test
Five t ablet s from each brand w ere selected random ly and
subject ed t o hardness t est by using M onsant o hardness
t est er.
Friability test
Friabilit y t est has been perform ed on t ablet s of each
brand of losart an pot assium and subjecting t o a uniform
t um bling m ot ion for a specified period of t im e i.e. 25
rot at ion/ m inut e for 4 minut es in m odel No. FOD-02
Roche friabilit or and t he w eight loss is determ ined.
Friabilit y test is done t o check if a t ablet abrades during
t ransport ation by t aking init ial and final w eight and
det erm ining t he w eight loss. The t ablet s from each brand
w ere re-dust ed and re-weighed. According t o t he USP,
t he t ablet s should not lose m ore than 1% of t heir t ot al
w eight.
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ISSN 0976 – 044X
W eight variation test
Tw ent y t ablet s from each brand w ere w eighed on
electronic balance and t he average weight w as
calculat ed. Each tablet w as t hen w eighed individually and
m axim um and m inim um values for t he weight of t he
t ablet w ere not ed.
Disintegration test
The disintegrat ion t est w as carried out in accordance t o
USP specificat ions by using Disintegrat ion Test er. Six
t ablet s from each brand w ere subject ed t o disintegrat ion
t est . One t ablet w as placed in each of t he six t ubes of t he
basket . Then disks w ere added t o each t ube of t he
basket . The t ime t aken for t he ent ire t ablet t o
disint egrat e com plet ely w as recorded in m inut es. Water
w as used as a m edium and t est w as perform ed at 50 RPM
for 30m ins at 37°C.
Chemical assay
The chem ical assay of film coat ed t ablet s of each brand
w as carried out according t o USP by using 0.1 N NaOH by
using a UV spectrophot om et er (M odel No. 1700,
Shim adzu, Japan).
Standard preparation
About 50m g of reference w orking st andard of losart an
pot assium w as w eighed accurat ely on elect ronic balance
and t ransferred int o a 100 m l volum etric flask. The
volume w as m ade up t o t he m ark and m ixed. 1 ml of t he
first dilut ion w as t aken int o anot her 25 m l volum et ric
flask and volume w as m ade up t o t he m ark.
Sample preparation
20 t ablet s w ere weighed on elect ronic balance and
average weight of t he tablet w as calculat ed. Tablet s w ere
grinded t o a fine pow der. Pow der equivalent t o about 50
m g of losart an pot assium w as w eighed accurately and
t ransferred int o a 100 m l volum etric flask. 1m l of t he
filtrat e was t aken int o anot her 25 ml volumet ric flask and
volume w as m ade up to t he m ark.
Procedure of assay
Bot h st andard preparat ion and sam ple preparat ion w ere
scanned bet w een 196–226 nm and t he absorbance w as
taken at the maximum wavelength (λm ax) at 224 nm using
dist illed w at er as blank solution.
% of Losartan potassium = (Absorbance of
sample/ Absorbance of standard) x 100
In-vitro Dissolution Test
The in vit ro dissolution t est of film coat ed t ablet s of each
brand w as carried out according t o USP. The dissolut ion
t est w as conduct ed using USP type II apparat us
(Pharm aTest Germ any t ype PTWS3) at 37±0.5°C and 50
rpm w it h six sections assem bly according t o t he USP 30
procedure. Dissolut ion m edia used w as dist illed w at er.
The m edium w as m aint ained at 37 ± 0.5°C. Sam ples w ere
assayed by a validat ed UV m et hod (M odel No. 1700,
169
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Int. J. Pharm. Sci. Rev. Res., 35(2), November – December 2015; Art icle No. 31, Pages: 168-172 ISSN 0976 – 044X

Shim adzu, Japan). The concent ration of each sam ple w as brands possessed good m echanical st rengt h w it h
det erm ined from a calibrat ion curve obt ained from pure sufficient hardness. The hardness of all brands w as found
2
sam ples of losart an pot assium . t o be w it hin limit s (<10 Kg/ cm ).

Parameters of dissolution test According t o t he USP, t he t ablet s should not lose m ore
t han 1% of t heir t ot al w eight. All t he brands w ere passed
M edium: Dist illed w at er m aint ained at 37±0.5 °C
t he friabilit y t est . The % friabilit y ranges from (0.0-0.2%).
Volume: 900 m l

Apparatus: 2 (Paddle t ype)

Speed: 50 RPM

Time: 30 minut es

Limits: Not less t han 80% (Q) of t he labeled am ount of

losart an pot assium is dissolved in 30 minut es.

Procedure of dissolution test

Six t ablet s w ere t aken and one t ablet w as placed in each

of t he six basket s. Dissolution t est w as carried out
Figure 2: Friabilit y Test
according t o above m entioned paramet ers. Aft er
com plet ion of 30 minut es, t he dissolved am ount losart an The average w eight s of t ablet s of six different brands of
pot assium w as det ermined by em ploying UV absorpt ion losart an pot assium w ere found in t he range of (132.5-
at the wavelength of maximum absorbance (λm ax) at 200.5m g). All t he film coated t ablet s passed t he w eight
about 256 nm on the filt ered port ion of solution under variation t est as the percent age of w eight variation w as
t est suit ably dilut ed w ith t he dissolut ion m edium t o a w it hin USP lim it s of ± 7.5% of t he average w eight .
concentrat ion of 0.01 mg/ m l in com parison w it h
reference w orking st andard solut ion having a
concentrat ion of 0.01 mg/ m l in t he same m edium using
dist illed w at er as blank solution.

% of losartan potassium = (Absorbance of

sample/ Absorbance of standard) x 100

Statistical analysis

The dat a of dissolut ion t est w as evaluat ed st at istically by

analysis of variance (ANOVA) and com parison am ong
m ean dissolution dat a w as m ade by Least significant
difference (LSD) t est .
Figure 3: Weight variation Test
RESULTS AND DISCUSSION
Disint egration t est w as carried out under USP
specifications. The t ablet s of different brands show ed
sm all differences in disint egration t im e ranges from (10-
14m ins). M aximum D- tim e w as 14m ins of brands F3 and
F5, and m inim um w as 10m ins of brands F4 and F6. The D
t im e m ust be in t he range of 30m ins for film coat ed
t ablet s as ment ioned in USP.

Figure 1: Hardness Test

The average hardness of t ablet s w as det erm ined by using

M onsant o hardness t est er. The hardness of all brands
2
ranges from (3.9-7.2 Kg/ cm ). M axim um hardness w as
2
observed 7.2 Kg/ cm for brand F6 and m inim um hardness
2
w as 3.9 Kg/ cm for brand F2. The t ablet s of different

Figure 4: Disintegrat ion t im e Test

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Int. J. Pharm. Sci. Rev. Res., 35(2), November – December 2015; Art icle No. 31, Pages: 168-172 ISSN 0976 – 044X

The chem ical assay of t ablet s w as carried out in
accordance w ith USP 30. 0.1N NaOH w as used as a
solvent . There w as no considerable difference in chem ical
assay of six brands. The result s of chem ical assay were in
t he range of 94.66% (F6) t o 108.23% (F3). The brands
show ed variat ion in t he percent age of assay but lie in t he
st andard lim it s (>75%) so t he t est w as passed for all
brands.
has a direct effect on t he bioavailability profile of t ablet
dosage form s because it can be used t o det erm ine t he
pat t ern of drug release in vivo .
Price variation of all t he brands w as checked and
com pared indicating a fact t hat all t he local brands are
less in price as com pare t o brand leader (F6) w hile having
sim ilar physicochemical propert y. Local brands t ook less
t im e t o dissolve and having all ot her param eters sim ilar
t o brand leader, but having low prices t han F6, indicating
t he fact t hat t hey are physicochemical equivalent w it h
brand leader w hich having a cost of Rs. 440/ 20 t ablet s.

Figure 5: Chemical Assay

Figure 7: Price com parison

The t ablet is called as ideal when it show s t he high value

Figure 6: Dissolution Test
The in vit ro dissolution t est w as carried out in accordance
w it h USP 30 by using Pharm aTest Germ any type PTWS3
and UV apparat us of Shim adzu Pharm a Spec 1700. The
m axim um average dissolut ion (110.0%) w as observed for
F5 w hile t he m inim um average dissolution (95.0%) w as
show n by F1. It has been report ed t hat dissolution rat e
of hardness, low disint egration t ime and readily dissolve.
In com parison, F6 brand m et t he ideal condit ions having
2
m axim um hardness 7.2 kg/ cm , disintegrat ion t im e 10
m ins and % dissolution 102.2%. It show ed t hat t he drug
w as prepared according t o t he GM P and cGM P. It also
show ed t hat t he concentrat ion of different form ulat ion
com ponent s w as added in reasonable am ount. The brand
F1 did not m eet t he ideal condit ions as it has m axim um
2
hardness 6.3 kg/ cm but disintegrat ion time is high as
com pared t o ot her brands and dissolution rat e is low est
95%.

Table 1: Different brands of Losart an Pot assium t ablet s

Sr# Brands Batch # M fg date Expiry date Pack size Price/ pack(Rs/ -)

1 F1 2v 02/ 14 02/ 17 2x10 220

2 F2 FK156 10/ 14 09/ 16 1x10 132

3 F3 T2770 08/ 14 08/ 16 2x10 295

4 F4 H8775 09/ 14 09/ 16 2x10 250

5 F5 032 08/ 14 08/ 16 2x10 198

6 F6 A4465 09/ 14 09/ 16 1x10 220

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Table 2: Com plet e Evaluat ion of all selected Brands

S. No Parameters F1 F2 F3 F4 F5 F6

1 Hardness (Kg/ cm2) 6.3 3.9 6.8 4.4 4.6 7.2

2 % Friability 0.2 0.0 0.1 0.0 0.0 0.0

3 W eight variation (± %) 132.5±7.5 161.5±7.5 161±7.5 180±7.5 200.5±7.5 156.5±7.5

4 Disintegration (min) 13 13 14 10 14 10

5 Chemical assay (%) 95.92 99.79 108.23 101.14 102.64 94.66

6 Dissolution (%) 94.6 101.7 100.8 107.17 110.4 102.3

7 Price/ tab (Rs/ -) 11.00 13.20 14.75 12.50 09.90 22.00

8 Price/ 20units (Rs/ -) 220 264 295 250 198 440

CONCLUSION ant agonist s and renin inhibit ors. Ann Pharmacot her, 27, 1993,
1495-503.
All t he select ed brands of losartan pot assium 50m g w ere
4. Goldberg M R, Bradst reet TE, M cWilliams EJ. Biochemical
physico-chem ically equivalent so if one brand is not
effect s of losart an, a nonpept ide angiot ensin II recept or
available in m arket , anyone of t he rest of t he brands can ant agonist , on t he renin angiot ensin aldost erone syst em in
be prescribed by t he physician. hypert ensive pat ient s. Hypert ension, 25, 1995, 37-46.

The result s of all t he t est s performed show ed t hat GM P 5. Eberhardt RT, Kevak RM , Kang PM , Frishman W H. Angiot ensin
and cGM P guidelines have been followed during II recept or blockade: an innovat ive approach t o cardiovascular
m anufact uring. The dissolution profile of all select ed pharmacology. J ClinPharmacol, 33, 1993, 1023-38.

brands w as in t he range of st andard lim it s so aft er it s
pharmacoeconomics evaluat ion it is recom mended t hat
anyone of t he select ed brands can be used according t o
t he financial st at us of t he patient s. All brands w ere
t herapeutically equivalent so pat ient s can use any brand
alt ernatively according t o his econom ic conditions.
6. Brunner HR, Nussberger J, Waeber B. Angiot ensin II blockade
com pared w it h ot her pharmacological met hods of inhibit ing
t he renin-angiot ensin syst em. J Hypert ens, 11 (suppl 3), 1993,
S53-S58.
7. Chiu AT, M cCall DE, Price W A. In vit ro pharmacology of DuP
753. Am J Hypert ens, 4, 1991, 282S-287S.

How ever, out of t hese six brands F5 and F6 show ed 8. Kang PM , Landau AJ, Eberhardt RT, Frishman WH. Angiot ensin
bet t er dissolution profile and F5 is com parat ively of low II recept or ant agonist s: a new approach t o blockade of t he
cost 198 Rs./ - 20t ablet s. renin-angiot ensin syst em. Am Heart J, 127(5), 1994, 1388-401.

9. Levy P.J., Yunis C., Ow en J., et al. Inhibit ion of plat elet
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Source of Support: Nil, Conflict of Interest: None.

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