Kurdistan Technical institute

Pharmacy department
Pharmacy Calculation

Quality Control Tests for Different Types of

Paracetamol Tablets
By
Dilas Mhamad
Hawzhin Nazhad
Rayan Hiwa
Ahmad Fayaq
Sazan Jaffar
Avan Star
Supervised
Dr. Hanar

i
 Summery

According to World Health Organization, the term quality control refers to the
sum of all procedures undertaken to ensure the identity and purity of a particular
pharmaceutical. Quality control is an essential operation of the pharmaceutical
industry. In addition to the apparent features of tablets, tablets must meet other
physical specifications and quality standards. These include criteria for weight,
weight variation, content uniformity, thickness, hardness, disintegration, and
dissolution. Thus, in this project, five types of paracetamol tablets from different
companies which are widely used in the private pharmacies in Hilla city were
subjected to quality control tests to indicate whether these products will fit to the
standard criteria of the United States Pharmacopeia or not. The data indicated
that all brands succeeded to pass most quality control tests with some
exceptions.

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 Acknowledgement

Contents
Abstract ……………………………………………………………… ii
Acknowledgement.......................................................................................iii
Contents.......................................................................................................iv
1. Introduction..............................................................................................1
1.1. Quality control........................................................................................1
1.1.1 Quality assurance..................................................................................1
1.1.2 Sources of quality variation..................................................................2
1.2 Paracetamol..............................................................................................3
1.2.1 Medical uses of paracetamol.................................................................3
1.2.2 Pharmacokinetics of paracetamol.........................................................3
1.2.3 Side effects of paracetamol...................................................................3
1.2.4 Dose and dosage forms of paracetamol................................................4
Aim of the study...........................................................................................4
2. Materials and methods..............................................................................5
2.1 Materials..................................................................................................5
2.2 Methods....................................................................................................5
2.2.1 Physical examination............................................................................5
2.2.2 Weight variation test.............................................................................6
2.2.3 Size variation test..................................................................................6
2.2.4 Friability test.........................................................................................7
2.2.5 Disintegration test.................................................................................8
2.2.6 Hardness test.........................................................................................9
3. Results and discussion...............................................................................11
3.1 Physical examination.............................................................................11
3.2 Weight variation.....................................................................................12
3.3 Size variation.........................................................................................12
3.4 Friability test..........................................................................................13
3.5 Disintegration test..................................................................................14
3.6 Hardness test..........................................................................................15
Conclusion..................................................................................................16
References..................................................................................................17

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1. INTRODUCTION
1.1. Quality control
The concept of total energy quality control refers to the produce a perfect
product by a series of measures requiring an organized effort by the entire
company to prevent or eliminate errors at every stage in production. Although
the responsibility for assuring product quality belongs principally to quality
assurance personnel, it involves many departments and disciplined lines within a
company. To be effective, it must be supported by a team effort [1].

Quality must be built into a drug product during product and process design, and
it is influenced by the physical plant design, space, ventilation, cleanliness, and
sanitation during routine production. The product and process design begins in
research and development, and includes preformation and physical, chemical,
therapeutic, and toxicologic considerations. It considers materials, in process
and product control, including specifications and tests for the active ingredients,
the excipients, and the product itself, specific stability procedures for the
product, freedom from microbial contamination and proper storage of the
product, and containers, packaging and labeling to ensure that container closure
systems provide functional protection of the product against such factors as
moisture, oxygen, light, volatility, and drug/package interaction. Provision for a
cross referencing system to allow any batch of a product to be traced from its
raw materials to its final destination in the event of unexpected difficulties is
required [2].

1.1.1 Quality assurance

The assurance of product quality depends on more than just proper sampling and
adequate testing of various components and the finished dosage form. Prime
responsibility of maintaining product quality during production rests with the
manufacturing department. Quality assurance personnel must establish control

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or checkpoints to monitor the quality of the product as it is processed and upon
completion of manufacture. These begin with raw materials and components
testing and include in process, packaging, labeling, and finished product testing
as well as batch auditing and stability monitoring [1].

1.1.2 Sources of quality variation

Because of the increasing complexity of modern pharmaceutical manufacture
arising from a variety of unique drugs and dosage forms, complex ethical, legal
and economic responsibilities have been placed on those factors is the
responsibility of all those involved in the development, manufacture, control and
marketing of quality products. A systematic effective quality assurance program
takes into consideration potential raw materials, manufacturing process,
packaging material, labeling and finished product variables [1].

For example, for parenteral products which should be sterile and isotonic, a
number of quality control tests have been used such as:

• Checking the bulk solution for filling, drug content, pH, color, clarity and
completeness of solution.

• Checking the filled volume of liquids or filled weight of sterile powder for
injection in final container at determined intervals during filling

• Testing for leakage from flame-sealed ampoules.

• Subject the product to physical examination (visually or mechanically) for
appearance, clarity and particulate contamination.

• Examining the sterility indicator placed in various areas of sterilizer for

each sterilization operation.

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 • Submitting the product for sterility testings other predetermined biological
tests to establish the safety and other parameters of the product.

On the other hand, the standard quality controls tests that can be used for solid
dosage direct compression tablets are:

• Checking the weight variation of tablets at predetermined intervals during

manufacturing.
• Checking the disintegration and/or dissolution time, hardness and
friability of the tablets at least during the beginning, middle and end of
production or at prescribed intervals during manufacturing.

• Testing soluble tablets for compliance with solution time requirements.

• Examining products by line inspection or other equally suitable means
and removing the defective units prior to packaging.

1.2 Paracetamol
Paracetamol (acetaminophen) belongs to the NSAIDs family. It is widely used
and well known by Iraqi population for headache relief and its antipyretic
effects. Paracetamol is available as over the counter drug (OTC) and it is
available in different dosage forms and different strengths [3].

1.2.1 Medical uses of paracetamol

Paracetamol is commonly used as analgesic and antipyretic in the treatment
fever and as well used to reduce from mild to moderate pain. It has weak anti-
inflammatory effects. Generally, paracetamol can be used to treat several
conditions such as headache, muscle ache, fever and cold, arthritis, backache,
toothache. Paracetamol combined with opioid pain is also used for severe pain
such as cancer pain and pain after surgery [3].

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1.2.2 Pharmacokinetics of paracetamol
The bioavailability of paracetamol is about 63-89% and its protein binding of it
1025%. Its metabolism is predominantly in the liver and its urinary excretion is
about 85-90% after administration [3].

1.2.3 Side effects of paracetamol

Usual side effects are nausea, vomiting, dark urine, yellowish skin, loss of
appetite and stomach pain. Paracetamol toxicity may cause liver damage and
skin reactions
[3].
1.2.4 Dose and dosage forms of paracetamol
The commercially available dosage form of paracetamol includes tablets,
caplets, capsules, effervescent tablets, suppositories, suspensions, parenteral
injections, chewable tablets, oral drops, syrups, elixirs and extended release
tablets. The recommended doses of paracetamol in different age groups are
listed in table 1.1.

Table 1.1 The recommended doses of paracetamol based on age of patients.

Aim of the study

In this project we subjected five types of paracetamol tablets from different
companies which are widely used in the private pharmacies in Hilla city to
quality control tests to indicate whether these products will fit to the standard
criteria of the United States Pharmacopeia or not. The types chosen were based
on price criteria (cheap, moderate and relatively expensive) and based on the

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manufacturer (local private and government factories and international factories
including Indian and European manufacturer).

2. MATERIALS AND METHODS

2.1 Materials
Paracetamol sheets from five different companies were bought from a native
pharmacy in Hilla city. The selected types included Safacetol (SAFA Co.),
Omol (NP Pharma Co.), Paracetol (SDI Co.), Apmol (AJINTA Co.) and
Supofen (BASI Co.) which are shown in Fig. 2.1.

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 Fig. 2.1 Different types of paracetamol used in project

2.2 Methods
2.2.1 Physical examination
Ten tablets where removed from the sheet and carefully examined by naked eye
to detect its physical properties (appearance, color, break line, any cracked edges
or any deformations), (Fig. 2.2) .The process was repeatedly performed for each
type of paracetamol from different companies.

Fig. 2.2 Physical examination of different types of paracetamol tablets

2.2.2 Weight variation test

Ten tablets where removed from the sheet and the weight of each tablet was
measured individually by H-digital sensitive balance (DENVER Instrument
/China), (Fig. 2.3). The mean and standard deviation were calculated and the
accepted values of variation of ±5% were measured and compared with the
standard deviation [4].

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Fig. 2.3 Four digits sensitive balance used for weight variation of different types
of
paracetamol tablets

2.2.3 Size variation test

Ten tablets were removed from the sheet and each tablet was placed in digital
caliper (WEILIANG Co./ China), (Fig. 2.4) to measure its height. The steps
were repeated the rest of the tablets and then mean and standard deviation were
calculated and compared with the accepted ±5% value [4].

Fig. 2.4 digital scale used for size variation of different types of paracetamol
tablets

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2.2.4 Friability test
Friability is the tendency of tablet to powder, chip or fragment and this can
affect the elegance, appearance and the consumer acceptance of the tablet, and
also added to tablet’s weight variation or content uniformity problem. We used
tablet friability tester (GUOMING CS-2 / China), (Fig. 2.5) to measure friability
of the different brand of paracetamol tablet.

Fig. 2.5 Friability tester used for used for different types of paracetamol tablets

The weight of 10 tablets of each brand of paracetamol where measured and the
tablets were loaded in the friability tester. The apparatus exposed tablets to
rolling and repeated shocks as they fall 6 inches in each turn within apparatus.
After 4 minutes of 100 cycles, the tablets were removed from the device,
brushed to remove any powders and weighed again. The percentage of weight
loss (Friability %) was calculated according to the following equation:

Where Winitial is the initial weight and Wf is final weight

Friability values more than 5% were considered as unacceptable based on the

USP
[4].

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2.2.5 Disintegration test
Disintegration is a process by which tablets are fragmented into granules or
small particles. It is defined as the time required for a group of tablets to
fragment into particles under a given set of conditions which is measured by
disintegration tester. This test is basic for tablets intended that administration by
mouth except those intended to be chewed before being swallowed or those that
should dissolve slowly in the mouth, e.g. lozenges, glyceryl trinitrate, or
effervescent tablets. Also, disintegration does not apply to similar types of
sustained-release tablets.

Before each step the apparatus (Disintegration tester \GUOMING CS-2 / China),
(Fig.2.6) was cleaned from any residue of another test. The tank of the device
was filled with distilled water and left to reach the desired temperature (37ºC).
Six tablets of paracetamol were used by putting one tablet in each basket of the 6
tubes and fixed by the specified disk. The device was operated to start
continuous immersing and lifting of the tubes in the tank. The tablets in each
tube were carefully monitored until disintegrated completely and the time was
recorded. The mean and standard deviation of the disintegration time were
calculated and compared between different paracetamol brands. Values less than
10 minutes (600 seconds) were considered as accepted values [4].

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 Fig. 2.6 Disintegrator apparatus used for different types of paracetamol tablets

2.2.6 Hardness test

Hardness test (crushing strength) is the load required to crushing the tablet when
placed on its edge. Hardness is the force required to break the tablet by diametric
compression tester. Usually, tablet hardness tester is a portable semi-automatic
electronic tablet hardness tester designed to accept tablet up to 30 mm in
diameter. Unfortunately, in our project, such device was not available, and a
manual hardness tester was used to perform this test.
The hardness of ten tablets was measured by placing 1 tablet each time in the
hardness tester (Campbel electronics \ China), (Fig. 2.7) and recorded the force
required to break or crack the tablet. The mean and standard deviation of the
hardness were calculated and compared between different paracetamol brands.
Based on the USP, conventional tablet hardness should range between 2.5 to 10
kg/cm2 [4]. Values outside this range were considered unaccepted results.

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Fig. 2.7 Manual tablet hardness tester used for different types of paracetamol
tablets

3. RESULTS AND DISCUSSION

According to World Health Organization (WHO), the term quality control refers
to the sum of all procedures undertaken to ensure the identity and purity of a
particular pharmaceutical [5]. Quality control is an essential operation of the
pharmaceutical industry. Drugs must be marketed as safe and therapeutically
active formulations whose performance is consistent and predictable. It not only
protects the manufacturer against compensation claims, but also guarantees the
patient a safe and effective product.

Thus, in addition to the apparent features of tablets, tablets must meet other
physical specifications and quality standards. These include criteria for weight,
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weight variation, content uniformity, thickness, hardness, disintegration, and
dissolution. These factors must be controlled during production (in-process
controls) and verified after the production of each batch to ensure that
established product quality standards are met.

3.1 Physical examination

The various types of paracetamol tablets were subjected to physical examination
using naked eye. The shape, engravings, color, sharpness of edges and extent of
powder loss were investigated and the results are listed in Table 3.1.

Table 3.1 Physical examination of different paracetamol brands

Product Description

Paracetol Round, white tablets with excessive loss of powders and irregular
edges. The tablets contain break-line with engraved with "500" sign.

Safacetol Round, white tablets with loss of powders and irregular edges. The
tablets contain a break-line with no engravings.

Sapofen Round, white tablets with moderate loss of powders and irregular
edges also. The tablets do not contain break-line nor any engravings.

Apmol Round, white tablets with excessive loss of powders and regular
edges.
The tablets contain break-line and engraved with "500" sign.

Omol Round, white tablets with excessive powder loss and few tablets with
irregular edges. The tablets contain a break-line with no engravings.
3.2 Weight variation
The average weights of ten paracetamol tablets of each brand were measured as
well as the standard deviation and the accepted values based on the ± 5%. The
results are listed in Table 3.2.

Table 3.2 Weight variation of different paracetamol brands

Product Weight (mg) SD Acceptable value Verdict

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 Paracetol SDI 616.07 9.19 30.80 Approved

Safacetol 605.73 6.31 30.28 Approved

Sapofen 681.64 10.72 34.08 Approved

Apmol 581.41 51.98 29.07 Rejected

Omol 555.93 7.11 27.79 Approved

The lowest weight variation was detected in Omol brand. The data indicated that
all types of paracetamol tablets were within the accepted range except the
Apmol type. The variation in weight in tablets dosage form may be caused by
several factors such as flow properties of powders, size and shape of particles
and the amount and type of excipients.

3.3 Size variation

The average size of ten paracetamol tablets of each brand were calculated as
well as the standard deviation and the accepted values based on the ± 5%. The
results are shown in Table 3.3.

Table 3.3 Size variation of different paracetamol brands

Product Size (mm) SD Acceptable value Verdict

Paracetol SDI 4.303 0.095 0.215 Approved

Safacetol 4.369 0.286 0.218 Rejected

Sapofen 4.273 0.255 0.233 Rejected

Apmol 4.273 0.096 0.213 Approved

Omol 4.137 0.124 0.206 Approved

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Two types of paracetamols (Safacetol and Sapofen) failed to pass the test of size
variation while the rest of the types were within the accepted range. The
Paracetol SDI and Apmol brands showed the best values with minimum size
variation.

The thickness of a tablet is determined by the diameter of the die, the amount of
fill permitted to enter the die, the compaction characteristics of the fill material,
and the force or pressure applied during compression. Many of these factors are
affected by the flow properties of powders, size and shape of particles and the
amount and type of excipients (glidants). To produce tablets of uniform
thickness during and between batch productions for the same formulation, care
must be exercised to employ the same factors of fill, die, and pressure.

3.4 Friability test

Friability is the phenomenon where the surface of the tablet is damage or shown
a site of damage due to mechanical shock. The purpose of the test is to evaluate
the ability of the tablets to withstand the breakage during the packaging,
transportation and handling. The average percentages of weight loss of
paracetamol tablets of each brand were calculated and the accepted values based
on the ± 5%.
The results are shown in Table 3.4.

Table 3.4 percentage of weight loss of different paracetamol brands

Product % Wt. loss Verdict

Paracetol SDI 7.71 Rejected

Safacetol 6.53 Rejected

Sapofen 7.29 Rejected

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 Apmol 0.2 Approved

Omol 0.24 Approved

The results revealed that only 2 brands of paracetamol (Apmol and Omol)
succeeded to pass the test. However, other brands (Paracetol SDI, Safacetol and
Sapofen) were out of the accepted range. The friability is affected by the type
and amount of binder, method of preparation and the force of compression.

3.5 Disintegration test

For the medicinal agent in a tablet to become fully available for absorption, the
tablet must first disintegrate and discharge the drug to the body fluids for
dissolution. Tablet disintegration also is important for tablets containing
medicinal agents (such as antacids and antidiarrheals) that are not intended to be
absorbed but rather to act locally within the gastrointestinal tract. In these
instances, tablet disintegration provides drug particles with an increased surface
area for activity within the gastrointestinal tract. All USP tablets must pass a test
for disintegration, which is conducted in vitro using a disintegrator testing
apparatus. The average disintegration time of different paracetamol brands were
determined and the results are shown in Table 3.5.

Table 3.5 Disintegration time of different paracetamol brands.

Product Disintegration Verdict
time ± SD (sec)

Paracetol SDI 109 ± 11 Approved

Safacetol 378 ± 68 Approved

Sapofen 161 ± 21 Approved

Apmol 34 ± 5 Approved

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 Omol 141 ± 21 Approved

The disintegration of all types of paracetamol tablets were accepted and below
the ten minutes threshold. However, the fastest time was shown by Apmol brand
(34 sec). The faster disintegration time will improve rate of dissolution rate of
absorption, bioavailability, rapid onset of action and faster response [6]. The
longest disintegration time was related to Safacetol brand which reached almost
7 minutes.

3.6 Hardness test

Generally, the greater the pressure applied, the harder the tablets, although the
characteristics of the granulation also have a bearing on hardness. Certain
tablets, such as lozenges and buccal tablets, are intended to dissolve slowly and
are intentionally made hard; other tablets, such as those for immediate drug
release, are made soft [6]. In general, tablets should be sufficiently hard to resist
breaking during normal handling and yet soft enough to disintegrate properly
after swallowing. A force of about 4 kg is considered the minimum requirement
for a satisfactory tablet. Multifunctional automated equipment can determine
weight, hardness, thickness, and diameter of the tablet. The average hardness of
different paracetamol brands were determined and the results are shown in Table
3.6. It should be kept in mind that this test was performed using a manual device
which gives rough results rather the automatic apparatus, thus results close to 10
kg/cm2 were considered as approved results.

Table 3.6 Hardness of different paracetamol brands.

Product Hraness ± SD Verdict
(Kg/cm2)
Paracetol SDI 12.21 ± 1.3 Approved

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 Safacetol 12.23 ± 1.1 Approved

Sapofen 11.01 ± 1.4 Approved

Apmol 10.32 ± 0.9 Approved

Omol 9.31 ± 1.1 Approved

Conclusion
The data indicated that all brands succeeded to pass most quality control tests
with some exceptions. It should be highlighted these results were obtained for
the specific batches used in the experiment, however, different results may be
obtained if different batches were used for the same products and this is the core
of quality control studies. One of the major tests of quality control for tablets is
the quantitative determination of the tablets contents especially for the active
ingredient(s). Unfortunately, this test was not performed in our project due time
and facility limitations. However, such test (quantitative determination of
paracetamol contents in each brand using high performance liquid
chromatography) could be included in any future work to shed more light on this
issue and strengthen the scientific aspects of the project.

References
1. Lachman, L., & Liebermann, H. A. (2013). The theory and practice of
industrial pharmacy. New Delhi: CBS Publishers & Distributors Pvt. Ltd.

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2. Shargel, Leon, Susanna Wu-Pong, and Andrew B. C. Yu. Applied
Biopharmaceutics & Pharmacokinetics. New York: Appleton & Lange
Reviews/McGraw-Hill, Medical Pub. Division, seventh edition, 2015.

3. McKay, Gerard A.; Walters, Matthew R. (2013). "Non-Opioid

Analgesics". Lecture Notes Clinical Pharmacology and Therapeutics (9th ed.).
Hoboken: Wiley.

4. The United States Pharmacopeia 32–National Formulary 27. Rockville,

MD: U.S. Pharmacopeial Convention, 2009.

5. Supplementary guidelines on good manufacturing practices: validation,

Appendix 4 on Analytical method validation, in WHO Technical Report Series,
No. 937, 2006, Annex 4, and ICH guideline Q2 (R1).

6. Fuhrman, L., Jr. (2006). Ansel's pharmaceutical dosage forms and drug
delivery systems, 8th edition. American Journal of Pharmaceutical Education,
70(3), 71 .

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