Albendazole
Albendazole
https://doi.org/10.20428/YJMS.11.1.A7
ABSTRACT
Objective: To assess certain quality control parameters for seven brands of albendazole tablets obtained
from different retail pharmacies.
Methods: The physicochemical properties and active ingredientsofseven randomly selectedbrands of al-
bendazole tablets were assessed weight uniformity, hardness, friability, disintegration and dissolution
Results: All seven albendazole brands met the British Pharmacopeia (BP) quality control standards of
weight uniformity, friability and the active ingredient content. Five brands met the BP disintegration criteri-
on,whereas only two brands complied with the BP quality control parameters of the dissolution specifica-
tions.
Conclusions: Out of the seven brands of albendazole (400 mg) tablets, only two fulfillthe BP quality control
standards and show physicochemicalquivalence. This emphasizes the need for regular assessment of mar-
keted drugs to assure equivalenceof these drugs to their innovators.
© 2017 University of Science and Technology, Sana'a, Yemen. This article can be unrestrictedly used, distributed or reproduced
in any medium, provided that credit is given to the authors and the journal.
46
Othman G.Q., Yemeni J Med Sci 2017; 11: 46–52.
https://doi.org/10.20428/YJMS.11.1.A7
© 2017 University of Science and Technology, Sana'a, Yemen. This article can be unrestrictedly used, distributed or reproduced
in any medium, provided that credit is given to the authors and the journal.
47
Othman G.Q., Yemeni J Med Sci 2017; 11: 46–52.
https://doi.org/10.20428/YJMS.11.1.A7
weight and the percentage weight variation dusted and re-weighed. Friability was calculated
from the mean value were obtained for each using the following equation (16):
brand. Appropriate tablet hardness and friabil- % Friability = (Wi – Wf) / Wi) 100
ity is attributed to weight controlling within a Wi= weight of tablet before friability
tight range, where the percentage weight vari- Wf = weight of tablet after friability
ation was ensured not to exceed 5% (16). The
average weight variations for all brands of al- Conventionally, compressed tablet weight loss
bendazole tablets were calculated mathemati- was generally ensured to be less than 0.5 to 1%
cally using the following equations (17): (17).
Highest weight variation = (Highest weight − Aver-
2.3.4. Disintegration time test
age weight/Average weight) 100
Lowest weight variation = (Lowest weight − Aver- Disintegration time of uncoated tablets was de-
age weight/Average weight) 100 termined using a USP disintegration tester (Elec-
trolab, Mumbai, India; Model: ED-2L) in 0.1 N HCl
Table 1. Identity and specification of albendazole brands includ- medium at 37±1 °C according to the British Phar-
ed in the present study*
macopoeia (BP) (16). For each albendazole brand,
Country Code Batch Manufacturing Expirydate
of origin number date
six tablets were selected and placed in separate cy-
France A 314567 01-02-2012 01-02-2017 lindrical tubes in a basket rack. The time required
India B 11al02 01-10-2011 01-09-2014 for each tablet to disintegrate and pass out
India C Kw2748 01-10-2012 01-09-2015 through the mesh was recorded, and the mean dis-
Yemen D 106t 01-02-2013 01-02-2016 integration time for each brand was then calculat-
India E 180212 01-09-2012 01-10-2015 ed (19).
Cyprus F 37909 01-09-2008 01-09-2013
South Korea G 7903p 01-10-2009 01-10-2014
2.3.5. Dissolution time test
* The strength of all brands was 400 mg.
Drug release pattern during a specific period was
determined by dissolution time testing (20). The
2.3.2. Hardness test
drug release pattern for each brand of albendazole
The hardness of 10 tablets selected randomly was determined using a dissolution tester (Pharma
from each brand was determined using a tab- Test, Hainburg, Germany; Model: PT-DT70). The
let breaking-strength tester (Germany, PHAR- dissolution process was carried out in a medium of
MA TEST: PTB). The hardness for each tablet 900 ml 0.1 N HCl using a speed of 50 rpm at 37±1
was recorded, and the mean hardness was cal- °C. Up to three 5-ml samples were withdrawn eve-
culated according to well-established equa- ry 10 minutes and replaced with the same amount
tions (18). of fresh dissolution medium. The obtained samples
were suitably diluted and analyzed for albendazole
2.3.3. Friability test
using high-performance liquid chromatography
Five albendazole tablets were dusted and (HPLC) at 254 nm using Shimadzu HPLC system
weighed together before friability testing us- (Shimadzu, Kyoto Japan), where the percentage of
ing a US Pharmacopoeia (USP)-compatible fri- drug release was calculated after measuring the
abilator Germany (PHARMA TEST: PTB) which absorbance (17, 20).
was set to run for four minutes at a speed of 25
rounds per minute (rpm). After removing the
tablets from the friabilator, they were
© 2017 University of Science and Technology, Sana'a, Yemen. This article can be unrestrictedly used, distributed or reproduced
in any medium, provided that credit is given to the authors and the journal.
48
Othman G.Q., Yemeni J Med Sci 2017; 11: 46–52.
https://doi.org/10.20428/YJMS.11.1.A7
2.3.6. Content uniformity test mean dissolution time ranged from 0.80 to 85.62
minutes. On the other hand, albendazole content
Active ingredient uniformity test of the tablets
uniformity ranged from 95.0 to 105.2 grams.
was carried out using HPLC (Shimadzu, Kyoto,
Japan). Methanol and buffer in a ratio of Table 2. Unofficial quality control parameters for seven brands of al-
700:300 were used as the mobile phase. The bendazole tablets (400 mg) marketed in Yemen
flow rate of the mobile phase was 2ml per mi- Brand Weight uniformity Crushing strength Friability
nute, and the injection volume of the sample code (mg) (KgF) (w/w)
was 20 μl. Albendazole detection wavelength (mean ± SD) (mean ± SD) (%)
A 1030.1 ± 1.9 13.9 ± 0.8 0.27
was set at 254 nm. Active ingredient chemical
B 7711.7 ± 0.5 23.68± 1.6 0.11
identification and content uniformity tests
C 1170.4 ± 1.2 20.5 ± 3.1 0.41
were carried out according to the BP, 2002
D 970.0 ± 1.4 10.18 ± 2.2 0.39
(35).
E 980.3 ± 1.6 14.04 ± 1.6 0.49
2.4. Data analysis F 910.9 ± 0.8 8.46 ± 0.3 0.36
G 930.1 ± 0.8 14.02 ± 1.9 0.03
Weight uniformity, hardness, friability as well
Limit ±5 >5kg/cm2 <1%
as disintegration and dissolution times of al-
bendazole tablets of each brand were analyzed SD, standard deviation
3.1. Weight variation, crushing strength and C 10.00± 0.313 0.80 ± 0.003 103.7±2.414
© 2017 University of Science and Technology, Sana'a, Yemen. This article can be unrestrictedly used, distributed or reproduced
in any medium, provided that credit is given to the authors and the journal.
49
Othman G.Q., Yemeni J Med Sci 2017; 11: 46–52.
https://doi.org/10.20428/YJMS.11.1.A7
to manufacturers’ errors (9, 27, 22). On the sent study showed that the friability values for all
contrary, these findings are not in line with albendazole brands were acceptable, ranging be-
previous studies from Yemen, Rwanda and tween 0.03% w/w and 0.49% w/w. Tablets with
Tanzania, which did not find substandard for- the highest crushing strengths showed a low fria-
mulations at purchase time (12, 23). bility value similar to those for ciprofloxacin
brands conducted elsewhere (28).
The quality of manufactured drugs might
be affected by several factors such as storage Tablet disintegration in the gastrointestinal
conditions, humidity, packaging materials, tract is an essential step for drug absorption and
transportation, formulation constituents and bioavailability, and subsequently therapeutic effi-
the nature of the active ingredient that is con- cacy of medicines (29). In the present study, the
sidered as the most important factor. When brands B and D showed the longest disintegration
the strength is greater than 250 mg, the tablet time of 30.0 minutes. However, the brand E
weight variation meets the requirements if not showed the least disintegration time of 4.25
more than two of the individual weights devi- minutes, which might be attributed to the presence
ate from the average weight by more than of a large amount of disintegrants. According to
±5% and none of them deviates by ±10% ac- the USP, the disintegration time of uncoated tab-
cording to the specifications outlined in the BP. lets is up to 15 minutes. Accordingly, the brands B
The present study showed that all brands of and D exceeded the allowed time, while other
albendazole tablets have acceptable uniformi- brands were within the acceptable limits. It is
ty of weight because none of the brands has a noteworthy that the batches with longer disinte-
percentage deviation in weight greater than gration times correlate with higher hardness and
5% as specified by the BP. lower friability values. On the other hand, the
brand B had the highest crushing strength and is,
Tablet hardness gives an insight as to the
therefore, expected to have a longer disintegration
tablet tooling used by various manufacturers;
time. This finding is in contrary with the fact that
a force of about 5 kg/cm is the minimum re-
tablets with high hardness and compression force
quirement for satisfactory hardness of tablets
values had short disintegration times (30). How-
(24, 25). Generally, all the studied brands
ever, the finding of this study is similar to other
passed the hardness and friability specifica-
studies showing that an increase in the tablet
tions of tablet dosage forms. In fact, the differ-
compression pressure leads to a longer disintegra-
ence in tablet sizes, such as weight, diameter
tion time (31, 32).
and thickness, may have negative psychologi-
cal impact on the clinicians and on their pa- Tablet dissolution is a necessary criterion for
tients since such a difference might rise up drug bioavailability. Therefore, tablet dissolution
doubt about the equivalence of brands (26). test is considered a critical quality control parame-
Regarding the unofficial tests all albendazole ter to ascertain batch-to-batch equivalence as well
brands fulfilled crushing strength/hardness as product uniformity (33, 34). It is noteworthy
specifications. The utmost hardness of 23.65 that the USP specifies the dissolution time to be
kg/cm2 was achieved by B product not more than 30 minutes (35). All tablets should
release the active gradient into the dissolution
Adequate hardness and friability of a tablet
medium in an amount not less than 60% of the la-
are necessary for consumer satisfaction (27).
beled albendazole. On the other hand, the BP state
The USP states that a tablet friability value
that not less than 70% of a drug should be released
should be less than 1% (36).The pre-
at 30 minutes (35). The findings of the present
© 2017 University of Science and Technology, Sana'a, Yemen. This article can be unrestrictedly used, distributed or reproduced
in any medium, provided that credit is given to the authors and the journal.
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Othman G.Q., Yemeni J Med Sci 2017; 11: 46–52.
https://doi.org/10.20428/YJMS.11.1.A7
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© 2017 University of Science and Technology, Sana'a, Yemen. This article can be unrestrictedly used, distributed or reproduced
in any medium, provided that credit is given to the authors and the journal.
51
Othman G.Q., Yemeni J Med Sci 2017; 11: 46–52.
https://doi.org/10.20428/YJMS.11.1.A7
© 2017 University of Science and Technology, Sana'a, Yemen. This article can be unrestrictedly used, distributed or reproduced
in any medium, provided that credit is given to the authors and the journal.
52