Mediterranean Journal of Pharmacy & Pharmaceutical Sciences

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

Original article

Post-marketing quality assessment of paracetamol brands in the Libyan market

Mostafa A. Almdaaf * , Mohamed S. Altriki and Mohamed A. Elnekaib

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Elmergib University, Al Khums, Libya

*
Author to whom correspondence should be addressed

Received: 12-11-2023, Revised: 06-12-2023, Accepted: 08-12-2023, Published: 31-12-2023

Copyright © 2023 Almdaaf 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

Almdaaf et al. (2023) Post-marketing quality assessment of paracetamol brands in the Libyan market.
Mediterr J Pharm Pharm Sci. 3 (4): 73-79. https://doi.org/10.5281/zenodo.10289340

Keywords: Brand, paracetamol, post-marketing, quality control

Abstract: Paracetamol is one of the most found over the counter drugs worldwide. It is widely used as an
analgesic and antipyretic drug. Many commercial types of paracetamol tablets are available under different
brand names in the Libyan drug market. The present study was conducted to evaluate post-marketing quality
parameters for three brands of paracetamol tablets marketed in Libya. All three brands were evaluated for
weight variation, hardness, friability, disintegration time and uniformity of content following British
pharmacopeia guidelines. The outcomes of this study showed all tested brands complied with the British
pharmacopeia specifications for the weight variation test, friability test (0.05%-0.17%), and hardness test
(171.3N-197.6 N). In addition, two brands passed the British pharmacopeia requirements for the disintegration
time test, whereas one brand exceeded the allowed disintegration time by about five minutes. Furthermore,
high performance liquid chromatography was used to determine paracetamol content. Although the average
amount of paracetamol drug available in these brands is not very close to 100%, where one brand achieved
the lowest value (438.1 mg), the loaded dose of paracetamol in selected tablets in the three brands was within
the British pharmacopeia standard specifications for the uniformity content test. Therefore, it can be concluded
that almost all the three tested brands of paracetamol tablets that are available in the Libyan drug market meet
the British pharmacopeia specification for quality control analysis.

Introduction and the World Health Organization (WHO) has

continuously recommended the use of generic
The safety, efficacy and bioavailability of drug
brands [3]. However, this has been associated with
products are directly depending on the drug quality.
many problems due to the widespread distribution
The quality control system for drug production
of fake and substandard drug products that are a
includes starting materials quality control, in-
major cause of morbidity, mortality, and
process quality control and finished final drug
diminished public confidence in drugs and health
product quality control as well as, post-marketing
structures [3, 4]. According to WHO, more than a
quality control assessments. Lack of adequate
quality control measures may occasion potential quarter number of drug products on sale for
consumption have been reported as counterfeit
toxicity or treatment failure and drug resistance [1,
products [5]. In Tanzania, 12.0% of marketed
2]. The introduction of generic drug products is
antimalarial drug products are reported as of main
expected to improve the overall healthcare system,
cause in the failure in the treatment of malaria

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disease [6]. Hence, post-market evaluations can be paracetamol tablets marketed in the Yemeni
used to judge the approved drug products for their market. The findings showed all brands of
safety, efficacy and quality. Fake drugs are paracetamol comply with British Pharmacopeia/
becoming a big public health problem as either they United State Pharmacopeia (BP/USP)
lose adequate efficacy or they have toxicity [7, 8]. specifications for in vitro quality control tests,
The prevalence of fake drugs is higher in countries except the hardness test, which is referred to as a
with weak regulations, enforcement, and non-official test. The study concluded that the
insufficiency of supply of basic drugs, also, overall quality of all tested brands of paracetamol
unregulated drug markets and unreasonable drug was acceptable. Furthermore, Sahle and others [16]
prices [9]. conducted an exclusively experimental study that
used BP/USP to evaluate the in vitro quality of
Paracetamol, is a widely used the analgesic and
paracetamol marketed in the Somali region of
antipyretic drug all over the world. Long-term
Ethiopia. The outcomes showed all of the brands
application and/or overdoses of paracetamol may
were within the specification for the weight
cause potentially fatal liver damage and/or renal
variation test. Nevertheless, from the illegal import
functioning disorder [10]. Successful therapeutic
brands, two for friability, one for disintegration and
efficiency of oral solid dosage forms, including
all for percentage of drug content failed to satisfy
tablets, depends mainly on the quality of a series of
the standards. The study has concluded that the
parameters, such as weight variation, hardness,
quality of illegal paracetamol was below the
friability, disintegration time, and dissolution rate,
standard in contrast to the legal paracetamol. There
which are affected by drug properties,
are some of post-marketing quality control studies
manufacturing methods and utilized excipients.
of paracetamol tablets that have been conducted in
Paracetamol tablet products of different
Libya. Khreit and others [17] tested ten brands of
manufacturers and/or sources are expected to
paracetamol that conformed to the USP/BP
measure varying quality parameters, however,
specifications. All the brands had shown their
within permitted limits to be considered successful
weight variation, hardness and friability measures
products. The quality of pharmaceutical dosage
satisfied with the range specified by USP/BP
forms has become a global concern, recently, as
limitations, in despite some apparent minor
counterfeit drugs are increasingly detected, and this
differences among them. The paracetamol content
concern has led to the necessity to evaluate the drug
test, which was carried out using HPLC showed
dosage forms available in the market. This
seven brands complied with the specification of BP
evaluation process is known as post-marketing
within the range of 90-110% stated content. While
quality control studies [11]. To date, a number of
three brands failed the content of active ingredient
post-marketing in vitro quality control studies have
test and did not comply with specifications. Rwaiha
been conducted to evaluate the physiochemical
et al. [18] carried out post-marketing in-vitro
properties of solid dosage forms [12, 13]. Islam et
studies for five brands of paracetamol marketed in
al. [14] analyzed four brands of paracetamol tablets
Libya. Excluding one brand which was failed the
by different physicochemical quality control
friability test by 20.0% deviations more than the
parameters. All the brand samples passed the
desired limit (1.0%), the study exhibited almost all
weight variation, hardiness, friability, and
of the selected brands of paracetamol assessed met
disintegration rate tests and they satisfy the
the BP specifications for quality control analysis.
specification limits. However, one brand sample
This study aimed to evaluate the legally registered
fail the dissolution test, as well as, another brand
paracetamol tablets in the Libyan market. These
sample fails the uniformity drug content test. The
brands were selected based on the differences in
results show that most of the brand samples satisfy
their manufacturing sources, their fast distribution
the specifications for all quality control parameters
and acceptability by the consumers, as well as, their
with low standard deviations. Alsaifi and Alyahawi
significant price difference.
[15] evaluated the quality of four brands of

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Materials and methods for the tablet to disintegrate. The beaker of the
disintegration tester was filled with 900 ml of
This study focused on evaluating various quality
deionized water at 37.0 ± 2.0 0C. Afterward, 6
control parameters for three brands of paracetamol
tablets were placed into the basket rack assembly
that are the most available products in the
and connected to the disintegration device. Finally,
government and private pharmacies. These quality
the disintegration time was recorded for the tablets.
control parameters includes weight uniformity,
hardness, friability, disintegration time and active Uniformity of content test: This test is based on the
ingredient content. Paracetamol 500 mg tablets of assay of the individual contents of the active
legally registered brands namely A, B, and C, were ingredients of several single-dose units. This assay
selected and coded, respectively. Paracetamol was performed in compliance with BP to assess the
reference standard powder was obtained from percentage content of paracetamol using the HPLC
Sigma Aldrich. Electronic analytical balance method. A standard stock solution of paracetamol
(ADAM AFP 110 L, India), tablet friability tester (250 mg/L) was prepared using the mobile phase.
(ERWEKA GmbH, Germany), TBH 125 tablet A series of working standard solutions in a range of
hardness tester (ERWEKA GmbH, Germany), (10-100 mg/L) were prepared by dilution from the
disintegration tester ZT 220 Series, (ERWEKA stock solution. Three sample solutions for the
GmbH, Germany) and HPLC 1260 Infinity Binary selected brands of paracetamol were prepared as
LC instrument (Agilent Technologies, Germany) well. The HPLC experimental measurement
were used to measure general and specific tests for procedure was conducted under the specific
quality of paracetamol tablets in compliance with conditions given in Table 1. A 10 μl aliquot of each
British pharmacopeia (BP) specifications. solution was injected into the column in three
replicates and the chromatograms were recorded.
Weight variation test: For each brand, 20 tablets
Thereafter, a calibration curve was constructed by
were selected at random, de-dusted and weighed
plotting the mean peak area versus the
individually using the electronic analytical balance.
concentration of paracetamol. The unknown
The average weight and deviations from that mean
concentration for the three paracetamol brands was
weight were calculated.
calculated from the regression equation derived
Friability test: This test was carried out by from the calibration graph.
selecting 20 tablets randomly from each brand, de-
Table 1: The HPLC experimental conditions
dusted and weighed using the electronic analytical
balance. Then, these tablets were placed in the Parameter Specific condition
drum of the friability tester and then operated at 25 Column Zorbax C18 (4.6 x 150 mm), 5 μm
rpm for four minutes (100 times rotation). Finally, Wavelength 243 nm
the tablets were de-dusted and re-weighed. The Mobile phase Methanol: water (40:60)
difference in the two weights was used to calculate Injection volume 20 μL
the friability value that was expressed in Flow rate 1 mL/min
percentage. Temperature Ambient

Hardness test: 10 tablets were selected at random

to carry out this test. Each tablet was placed Results
vertically on the TBH hardness tester. The load was
In this study, standard methods and procedures
then applied along the radial axis of the measuring
following the BP were used to conduct each test.
tablet. The load or weight required for breaking the
Thus, a total of three paracetamol brands legally
tablet was recorded. It was also done for all the
registered and marketed in the Libyan drug market
selected brands of paracetamol tablets.
were assessed for weight variation, friability,
Disintegration time test: A disintegration tester ZT hardness, disintegration time and content
220 Series was used to determine the required time uniformity. All of the brands of paracetamol

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investigated were within their shelf lives and treatment within the disintegration apparatus, and
immediate release dosage forms with a label it showed a disintegration time value of 19.5 min
strength of 500 mg. The results of the weight (Table 3).
variation test for all the brands revealed values that In Figure 1, The HPLC method for quantitative
complied with BP specifications as none of the analysis of paracetamol content in all brands has
brands deviated by up to ± 5.0% from the mean been used. The HPLC assay for paracetamol
value as shown in Table 2. On the other hand, content analysis showed a well-defined
Table 3 describes the results of hardness and chromatographic separation within a run time of six
friability tests. All the brands passed the non- min. It exhibited a retention time of paracetamol at
official hardness test according to BP, as none of 2.62 min ± 0.04 % (RSD), as well as, a standard
the obtained values exceeds 400 N. The friability paracetamol linear calibration curve with a
test revealed values that complied with BP linearity relationship in the range of 10-100 mg/L,
friability specifications as the percent friability for
a regression equation is Y = 84.943X and a
all assessed paracetamol tablets was less than 1.0%. correlation coefficient (r) of 0. 999. The outcomes
This indicated that all the tablets of each brand of the uniformity of drug content tests showed all
were mechanically stable. Furthermore, the results the assessed paracetamol brands complied with the
of this study showed that all the brands have passed BP standard specifications for the uniformity
the disintegration time test according to BP, except content test as displayed in Table 4.
brand B which has left core mass after 15 min of

Table 2: Weight variation tests of different paracetamol brands

Brand Average weight Permissible weight variation Real measured weight Percentage of
code in mg, n=20 range (mg) based on BP (±5%) variation range (mg) deviation range

A 676.99 710.84 - 643.14 687.10 - 664.50 (1.49%) - (-1.85%)

B 643.59 675.76 - 611.42 664.20 - 626.90 (3.20%) - (-2.59%)

C 602.28 632.39 - 572.16 625.52 - 585.22 (3.85%) - (-2.83%)

Table 3: Hardness and friability tests of different paracetamol brands

Hardness Friability tests

Brand tests
code (Newton) Weight before Weight after the Percentage of
n=10 The test (g) The test (g) Weight loss
n=10 n=10
A 171.3 6.7566 7.4480 0.17%
B 197.6 6.4892 6.4856 0.05%
C 194.5 6.0277 6.0184 0.15%

Table 4: Disintegration time and uniformity of drug content tests of different paracetamol brands

Uniformity of drug content

Brand Disintegration
code Time Branded Real measured Percentage of
(min) paracetamol paracetamol drug content
amount/tab (mg) amount/tab (mg)
A 3.4 500 473.2 94.6%
B 19.5 500 450.9 90.1%
C 1.5 500 438.1 87.6%

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Figure 1: Calibration curve of paracetamol standard obtained using HPLC

Discussion disintegration time test is performed to estimate the

time required to disintegrate the tablet in a gastric
All the brands of paracetamol tablets investigated
environment. According to BP specifications,
in the present study were within their shelf lives
conventional uncoated tablets were expected to
and immediate release dosage forms with label
disintegrate within 15 min. The findings show only
strength of 500 mg. The different quality
two brands of paracetamol tablets complied with
parameters of different brands of paracetamol were
the disintegration time test, where one brand
evaluated. The physical appearance of the various
achieved the shortest time (1.5 min). While one
examined brands of paracetamol tablets was satisfy
brand exceeded the allowed disintegration time by
with BP specifications. Tablet weight is mainly
about 5 minutes. Additionally, the current study
affected during the compression process by factors
displays the results of the test for the percentage of
such as machine speed, head pressure, and the
drug content which is based on the assay of the
tablet powder or granulate density and particle size
individual content of active ingredients of several
distribution. Therefore, uniformity of weight is an
single-dose units. BP specifies the brand passes the
in-process test parameter which used to show the
test if 9 of the 10 tablets contain not less than 85.0%
content uniformity of drugs. In this study, all of the
and not more than 115.0% of the labelled drug
examined brands of paracetamol tablets did not
content and the 10th tablet may not contain less than
deviate more than 5.0% of their average and this
75.0% and more than 125.0% of the labelled
complies with the BP specification for the weight
content. Although the outcomes of this study of
uniformity test. In addition, the friability test is
drug assay of three different brands of paracetamol
used to evaluate how well the tablets stand up to
showed that the average amount of paracetamol
coating, packing, shipping and other processing.
drug available in all these brands is not very close
According to BP specification, no tablet should
to 100%, where one brand achieved the lowest
show any type of break or crack and the total
value (438.1 mg), the loaded dose of paracetamol
weight loss should not be more than one percent. In
in selected tablets in all three brands was within the
this study, all the brands of paracetamol tablets
BP standard specifications for the uniformity
complied with the specifications set by BP, and
content test. Thus, the outcomes of this study were
their percentage loss of mass was less than 1.0%.
Moreover, sufficient tablet hardness is essential comparable to the results observed from the
previous quality assessment studies of paracetamol
and conducted to assess the ability of tablets to
tablets [17 and 18], and this proves the reliable
withstand mechanically. Hardness test values were
results of the current study.
within the limit of less than 400 N. Furthermore, a

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Conclusion: Despite one brand that failed the obtained from the present study were similar to the
disintegration time test and exceeded the allowed outcomes observed from the previous quality
BP limit test by about 5 minutes, the overall quality assessment studies of paracetamol tablets. Thus,
evaluation results of the three brands of this supports that paracetamol brands in Libya
paracetamol assessed in the Libyan market were to showed reliable quality standards.
verify with BP quality requirements. The results

Author contribution: All authors contributed equally 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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