Mediterranean Journal of Pharmacy & Pharmaceutical Sciences

www.medjpps.com ISSN: 2789-1895 online ISSN: 2958-3101 print

Short communication

A comparative evaluation of furosemide tablets marketed in Libya

Shahrazad A. Eteer 1 * , Jamal A. Elbakay 1 , Nesrine A. Almashai 1, Hayam A. Maree 1
Safa S. Elgadi and Tariq K. Almog 1
1

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tripoli, Tripoli, Libya

*
Author to whom correspondence should be addressed

Received: 20-11-2023, Revised: 10-12-2023, Accepted: 14-12-2023, Published: 31-12-2023

Copyright © 2023 Eteer et al. This is an open-access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HOW TO CITE THIS

Eteer et al. (2023) A comparative evaluation of furosemide tablets marketed in Libya.
Mediterr J Pharm Pharm Sci. 3 (4): 83-89. https://doi.org/10.5281/zenodo.10389843

Keywords: Furosemide, Libya, pharmaceutical equivalence, quality control evaluation

Abstract: Furosemide is a widely potent diuretic drug used in the management of edema and hypertension.
Various brands of furosemide are available in the Libyan market and should be subjected to different quality
control tests to assess their pharmaceutical equivalence. This study aimed to assess and compare the quality and
the pharmaceutical equivalence of some generic brands of furosemide 40 mg tablets marketed in Libya. The
pharmaceutical quality of four brands of furosemide tablets was investigated using official and unofficial
compendia standards including uniformity of weight, friability, thickness, hardness, drug content and dissolution
rate. The results obtained showed acceptable external features as well as the thickness, diameter and uniformity
of weight for all the furosemide tablets. The tested brands complied with the official specifications of friability,
hardness and drug content. In conclusion, all four brands can be considered as bioequivalence and thus can be
pharmaceutically substituted in clinical practice.

Introduction
Most patients with hypertension need drug treatment failure as well as severe hypertension [2]. It is white,
to reduce their blood pressure. There are different crystalline powder with molecular weight of 330.7
groups of anti-hypertensive drugs used to control g/mol [3]. Tablets are the most commonly preferable
blood pressure such as calcium-channel blockers, oral dosage forms that contain active ingredients in
diuretics, β-blockers, angiotensin-converting combination with excipients to provide desired
enzyme inhibitors and angiotensin II receptor properties that can affect the stability and the
blockers. Diuretics and calcium channel blockers are effectiveness of the formulation [4]. Tablets are
two of the most significant groups used for prepared by compressing the powder or granulated
hypertension treatment [1]. Furosemide, 4-Chloro2- mixtures using a tablet machine [5, 6] deliver the
[(furan-2-ylmethyl) amino]-5-sulfamoylbenzoic acid correct dose of the drug with the protection of its
(C12H11Cl N2O5 S), is a potent diuretic drug used in chemical integrity to the desired location of action
the management of edema, acute and chronic heart [7]. Coated tablets are tablets coated with an inert

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 Mediterranean Journal of Pharmacy & Pharmaceutical Sciences
www.medjpps.com ISSN: 2789-1895 online ISSN: 2958-3101 print

substance to protect the drug from dissolution in Materials and methods

gastric juice; however, tablets should freely dissolve Furosemide tablets with a label strength of 40 mg
and liberate the drug in the intestines [5, 6]. After oral were purchased from local pharmacy stores in
administration of the drug, the absorption is Tripoli City, Libya. All the tests were performed
sometimes incomplete because of improper within product expiration dates. The furosemide
dissolution and thus it leads to the insufficient powder standard (99.6%) was obtained from Sigma
amount of drug reaching the bloodstream [8]. Aldrich Co. LLC., USA. All the reagents and
Generic drug products are chemically equivalent to solvents used were of pharmaceutical grade. Study
their brand name counterparts in terms of containing samples were coded as shown in Table 1
the same amount of active ingredients in identical
dosage forms, strength, and route of administration, Table 1: Commercial furosemide tablets available in the
Libyan market
quality, purity, and intended use but may differ in
color, shape, excipients, labeling and the expiration Brand Name Manufacturer
A Furo-Denk XXXX
date [9-11]. The use of generic medicines has been
B Lasix XXXX
increasing in recent years as a real competitor for the C Lasilix XXXX
innovator ones due to their lower costs. [12-14]. D Furosemide XXXX
However, this could lead to the existence of
counterfeit or substandard medicines in higher The following instruments were used for the in vitro
percentages particularly in developing countries with quality control assessment of furosemide tablets.
the lack of supply of essential medicines, Assay by UV-spectroscopy, analytic Jena-spaced,
unaffordable prices and poor drug quality regulatory 200, model, Germany, tablet combination tester for
systems [11-14]. Although the parent drug is a hardness, diameter and thickness, friability tester,
cutting-edge product that is available to use with disintegration time tester apparatus, dissolution tester
advantages of high quality and effectiveness, DT50. Visual inspection: The diameter and thickness
however, it can be expensive for some patients. For of the four tablets from each brand were measured
this reason, some patients may prefer taking generic and the average value and standard deviation were
products with lower cost over the high cost of some calculated.
branded products. Evaluation of the physicochemical
Weight variation: Twenty tablets from each brand
characteristics of different brands of pharmaceutical
were randomly selected and their weights were
products is very important to assess their
measured. Then the average weight of each brand
bioavailability and pharmaceutical equivalence.
was calculated and the percentage deviation of each
When the generic product displays bioequivalence
tablet weight from the average weight and the
and therapeutic equivalence with the innovator,
standard deviation were determined.
interchangeability is allowed [15]. The quality of the
drugs can be evaluated using in vivo or in vitro tests Hardness test: The hardness, thickness, and diameter
[16]. of the tablets were determined using a tablet
combination tester. In the hardness test, twenty
In order to assess the physicochemical properties of
tablets were randomly selected from each brand and
pharmaceutical products, various tests are utilized as
the pressure was applied and the force required to
friability, hardness, weight variation, content of the
break up the tablet was recorded in newtons (N). The
active ingredient, disintegration and dissolution [17,
average force and the standard deviation of each
18]. The present study was conducted to evaluate and
sample were calculated [3]. Tablet thickness and
assess the quality of four furosemide tablet brands
diameter should be controlled within ± 5.0% of a
available in the Libyan market and to ascertain that
standard value [19, 20].
all the tested brands are pharmaceutically equivalent.

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Friability test: Twenty tablets were randomly taken their contents are within the accepted range. All the
from each brand and the loose dust was removed then brands of furosemide tablets were consistent in their
the tablets were accurately weighed and placed in the weight and showed uniform geometrical dimension
friabilator. The samples were allowed to rotate with parameters (Table 2 and Figure 1). Tablets of the
a total of 100 revolutions (25 rpm/min) then they same formulation should have the same appearance
were removed, de-dusted and reweighed and the in terms of color, shape and size. The deviation of
percentage of friability for each brand was calculated tablet weight from the average weight was within the
using the following formula acceptable limit that none of the tablet weight were
initial weight - final weight deviated from the average weight by ±7.5%. The
Friability (%) = initial weight
× 100
difference in the average weights could be a result of
Dissolution test: The in vitro release of the drug was using various excipients with different
investigated by USP dissolution test apparatus II, characteristics and properties during their
using a dissolution tester. The test was performed in preparations. All the brands revealed similar
900 ml of phosphate buffer pH 5.8 maintained at thickness (2.2-3.3 mm) and diameter of about 8 mm
37±0.5 °C and the apparatus was operated at 50 rpm. except sample A its diameter was 5.98 mm. Both the
Samples were withdrawn at intervals of 15, 30, 45, thickness and diameter of the tablets are important
and 60 min, filtered, diluted and the absorbance was factors for patient compliance and drug efficacy.
measured at 277 nm using pure medium as a blank. Ensuring the consistency of tablet thickness during
The percentage of average drug release for each batches of the same formulations can be
brand was plotted against time. accomplished by using the same compression force
for the same amount of the drug-filled in the
Assay of furosemide tablets: Twenty tablets were
machine. The same dosage forms of different
weighed and powdered. A quantity of the powder
manufacturer origin should not be expected to have
containing 0.2 g of furosemide was mixed with 300
the same properties and efficacy and as a result,
ml of 0.1 M sodium hydroxide for 10 min. A
evaluation of these brands to investigate their
sufficient amount of 0.1M sodium hydroxide
characteristics and their bioavailability is important
solution was added to produce 500 ml and the
to ensure their bioequivalence [21-23].
solution was filtered. 5 ml of the filtrate was diluted
to 250 ml with 0.1 M sodium hydroxide solution and Hardness test: The tablets should be of a suitable
the absorbance of the resulting solution was mechanical strength to tolerate any erosion or
measured at the maximum at 271 nm using a UV- chipping that can happen during handling,
VIS spectrophotometer and the percent content was manufacturing and transportation [24]. The results
determined. showed that the hardness of all the tested samples
was in the range of 67.6-100.3 N (Table 2). A force
Results and discussion of 40 N is the minimum requirement to achieve an
acceptable hardness of the tablets. Accordingly, all
Four commercial brands of furosemide tablets were
the tested tablets had satisfactory hardness. Brand C
assessed to evaluate their pharmaceutical quality to
showed to have the highest hardness while brand D
reduce the existence of poor-quality drugs in the
had the lowest value of hardness which indicated that
market. All the brands were subjected to various
brand C required the highest pressure load to cause
official tests to assess their dissolution and other
tablet to break up compared to other samples. Brand
valuable parameters such as weight variation,
C has been shown to have the lowest percentage of
hardness, friability and the drug content assay.
weight loss and the highest hardness compared to
Weight variation: This test is used to confirm that other tested brands. Hardness is an important tool
each batch contains tablets of appropriate size and that can affect the disintegration and dissolution rate

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www.medjpps.com ISSN: 2789-1895 online ISSN: 2958-3101 print

of the tablet [24]. Hardness has a direct relation with to be completely dissolved in gastrointestinal fluid
the friability and disintegration of the tablets. before their absorption [32]. In vitro dissolution test
Manufacturing of harder tablets will lead to an measures the time required for the tablet to release
inadequate dissolution rate with an increase in their the specified percentage of a drug into a solution
disintegration time [25-27]. In contrast, less hard under specified conditions and this parameter can be
tablet is expected to be more friable and take less used to provide information about drug absorption
time to disintegrate which in turn will affect the and bioavailability [33, 34]. The dissolution profiles
drug's bioavailability [28]. Thus, it is of important of four investigated generic drugs (released drugs)
requirement to assess the tablet hardness as it can were within the limit range (Figure 2) since the drug
lead to possible bioavailability issues or a change in release values were more than 80% in 60 minutes
the dissolution rate of the drug. (Figure 3).
Friability test: The percentage friability of the tested 9
Diameter mm Thickness mm
samples was in the range of (0.1-0.4%) as shown in
8
Table 2 which inferred that all the tablets were
within the limit percentage friability should be less 7
than 1.0% according to USP specification [29]. 6
Accordingly, all the tablets had good strength that 5
could resist any chipping or shock during their
mm
4
handling and transportation. The percentage of
friability decreases as the hardness of the tablet 3
increases and vice versa. The high friability is an 2
indication to the chipping or erosion of the tablet that
1
may cause the loss of the active ingredient and thus
could lead to weight variation or content uniformity 0
A B C D
problems [30, 31].
To ensure complete absorption of the orally Figure 1: Thickness and diameter (mm) of the
administered drugs in tablet dosage form, they have furosemide tablet brands

120

100
% Drug Release

80

60

40

20

0
0 10 20 30 40 50 60
Time/minutes
Brand A Brand B Brand C Brand D

Figure 1: Dissolution profile of different brands of furosemide tablet

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105 Content of active ingredient (assay): The content of

furosemide was determined in all the tested brands
100 99.03
and ranged from 95.0% (D) to 99.1% (A) as shown
in Table 2 and Figure 4 which were within the
95
% Drug release

specified limit (95-105%). Assay of pharmaceutical

90 88.03 products is a critical test to ensure that the dosage
87.16
85.69 form contains the labeled amount of drug where the
85 pharmaceutical products are considered of poor
quality if they fail to contain the right amount of the
80
active ingredient [35, 36]. An inadequate amount of
75 the drug can lead to under dosing and incorrect
A B C D treatment whereas higher amount of active
ingredients can lead to poor therapeutic outcomes
Figure 2: Dissolution rate profiles for furosemide tablet
brands at 60 minute
with an increased risk of adverse drug reactions and
toxicity.

Table 2: Physicochemical properties of different brands of furosemide tablet

Brand Average weight % Weight Diameter Thickness Hardness Friability Assay in

(mg) variation (mm) (mm) (N) (%) %

A 100.87 ±1.88 5.98 3.25 70.3 0.38 99.1

B 162.49 ±1.57 8.14 2.28 74.8 0.33 99.03
C 156.92 ±2.18 8.00 2.21 100.3 0.11 95.1
D 217.51 ±1.58 8.03 3.22 67.6 0.44 95

100 Conclusion: The generic brands of furosemide

99.1 99.03 tablets available in the Libyan market complied with
99
pharmacopoeia standards in which there was no
98
significant variation in the quality of those tested
% Drug content

97
brands. Therefore, it can be concluded that
96 furosemide brands are pharmaceutically equivalent
95.1 95
95 and can be interchangeable in clinical practice. This
94 study highlights the importance of strict monitoring
93 of pharmaceutical products in the markets especially
92 in developing countries to ensure the quality and
A B C D therapeutic equivalence of the products.
Figure 4: Content of furosemide brands in percentage

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Acknowledgments: Acknowledgments The authors are very grateful to the National Center for Food and Drug Control, Tripoli
for the help and facilities provided.
Author contribution: NAA, HAM and SSE designed the study, and collected the data. JAE, TKA & SAE Contributed in data
analysis and interpretation of data. All authors drafted, revised the manuscript and approved the final version of the manuscript and
agreed to be accountable for its contents.
Conflict of interest: The authors declare the absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Ethical issues: Including plagiarism, informed consent, data fabrication or falsification, and double publication or submission have
completely been observed by authors.
Data availability statement: The raw data that support the findings of this article are available from the corresponding author upon
reasonable request.

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