WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Awemu et al. World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 5.210

Volume 4, Issue 08, 37-45. Research Article ISSN 2278 – 4357

IN VITRO EVALUATION OF QUALITY CONTROL PARAMETERS

OF PARACETAMOL TABLETS IN NIGERIA
*
Awemu G.A.1, Anowi F.2, Ramos G.F.3 and Tejano G.I.4

Departments of Pharmaceutical Chemistry1 and Pharmacognosy3 Faculty of Pharmacy;

Department of Industrial Chemistry4, Faculty of Science, Madonna University, Elele, Rivers
State, Nigeria.
2
Department of Pharmacognosy and Traditional Medicine, Faculty of Pharmacy, Nnamdi
Azikiwe University, Awka, Nigeria.

ABSTRACT
Article Received on
25 May 2015, Paracetamol is an over-the-counter analgesic and antipyretic medicine
Revised on 16 June 2015, that is used all over the world. The aim of the present study was to
Accepted on 07 July 2015
assess the in vitro quality control parameters through the evaluation of
weight uniformity, hardness, friability, disintegration time, dissolution
*Correspondence for rate and the content of active ingredient of 20 brands of paracetamol
Author
tablets (BP 500 mg) purchased from registered pharmacies in three
Awemu G.A.
major Nigerian cities of Abuja, Benin and Onitsha. Qualitative
Departments of
Pharmaceutical Chemistry identification tests for the presence of active ingredient was carried out
Faculty of Science, and the organoleptic properties of all the 20 brands of paracetamol
Madonna University, were also assessed. Results obtained revealed that all the samples had
Elele, Rivers State,
uniform organoleptic properties and contained the active ingredient as
Nigeria.
indicated by the positive colour reaction test and Passed the weight
uniformity, hardness and dissolution test in phosphate buffer (pH 5.8) at 37o C. However, 30,
25 and 10 % of the drug samples failed tests for disintegration, friability and content of active
ingredient respectively probably due to poor storage and / or inappropriate in process quality
control assessment.

KEY WORDS: In Vitro, Quality, Paracetamol, Tablets, Nigeria.

INTRODUCTION
One of the greatest problems facing health care delivery in Africa is the infiltration of
counterfeit and substandard drugs into the drug distribution chain. A counterfeit medicine is

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Awemu et al. World Journal of Pharmacy and Pharmaceutical Sciences

defined by the World Health Organization (WHO) as one which is deliberately mislabelled
with respect to identity and / or source. Drug counterfeiting can apply to both branded and
generic products and may include products with the correct ingredients or with the wrong
ingredient, without active ingredient, insufficient active ingredient or with fake packaging
(Wondemagegnehu, 1999). Counterfeit and substandard pharmaceutical drugs apart from
leading to treatment failure and death can also engender lack of confidence in the health care
system (Newton et al., 2006). There is therefore a need to routinely assess the pharmaceutical
quality of drugs in Nigeria.

The trade in substandard and counterfeit drugs is thriving in third world countries because of
the ineffective law enforcement of existing legislation on drug counterfeiting, non healthcare
professionals in the drug business, the high cost of drugs, greed and corruption (Erhun et al.,
2001). Antibiotics, analgesics and antimalarials are the most commonly counterfeited drugs found in
Africa because they are easy to produce and market, (Ohuabunwa, 2002).

Paracetamol or acetaminophen is a very popular and widely used analgesic, anti pyretic and a
mild antiinflammatory medication (Bertolini et al., 2006; Karmakar and Kibria, 2012;
Bloomfield, 2002), that is very cheap and readily available as an over the counter preparation
(Zaid et al., 2013). In contrast to salicylates, the side effects of paracetamol are usually mild
and transient (Oscier et al., 2007). However, severe diarrhoea, increased sweating, loss of
appetite, nausea and vomiting, stomach cramps or severe pain, swelling, tenderness and pain
in the upper abdomen could all be signs of overdose (Koppert et al., 2006). Paracetamol is
one of the most commonly available pharmaceutical drugs in Nigeria (Oladimeji and Iranloye,
1990) and is marketed as generic drug products registered under various trade names by the
National Agency for Food Drug Administration and Control (NAFDAC), the Nigerian
equivalent of the Food and Drug Administration of the United States of America.

Treatment failure and drug resistance are frequently reported in developing countries due to
the inability of such countries to ensure an effective means of monitoring the quality of
generic drug products in the market (Ogwal – Okeng et al., 2003). It was in view of this fact
that the World Health Organization (WHO) issued guidelines for global standard and
requirements for the registration, assessment, marketing, authorisation and quality control of
generic pharmaceutical products (Nnamdi et al., 2009). Generic drugs are therefore expected
to satisfy the same standard of quality, efficacy, and safety as those applicable to the
innovator products (WHO, 1996). In this study, evaluation of the in vitro pharmaceutical

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 Awemu et al. World Journal of Pharmacy and Pharmaceutical Sciences

qualities of paracetamol tablets bought from three Nigerian cities was done by carrying out
identity test, weight uniformity, dissolution rate, disintegration time and content of active
ingredient. . Hardness test and evaluation of the organoleptic properties of the drug samples
involved in the study were also carried out.

EXPERIMENTAL
CHEMICALS AND DRUGS
Twenty brands of paracetamol tablets with a label strength of 500 mg were purchased from
Abuja, Benin city and Onitsha respectively. The drugs were then coded (PA1 – PA20) to
represent the various brands and visual inspection was done on all the samples for
information such as batch number, manufacturing and expiry dates and NAFDAC registration
status (Table 1).

Table 1. Lable information on paracetamol samples used in the study

Drug Code Batch no. Months to Expiration NAFDAC Reg. Status Place of purchase
PA1 LOT 9044 13 Present Benin
PA2 W253 13 Present Benin
PA3 2759P 7 Present Abuja
PA4 LOT615 17 Present Abuja
PA5 025R 22 Present Abuja
PA6 0201 15 Present Benin
PA7 503A NA Absent Benin
PA8 F10410 25 Present Benin
PA9 184 18 Present Benin
PA10 TA34247 21 Present Benin
PA11 H45 21 Present Benin
PA12 CL8015 NA Present Benin
PA13 PA530 11 Absent Benin
PA14 T8909 15 Present Benin
PA15 BVQ1 22 Present Onitsha
PA16 IZ707 18 present Onitsha
PA17 RG-9192 18 Present Onitsha
PA18 11 24 Present Onitsha
PA19 12 NA Present Onitsha
PA20 075 NA Present Onitsha
NA = Not available

Other important information such as manufacturer’s name, address and trade names were
noted but witheld.

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Awemu et al. World Journal of Pharmacy and Pharmaceutical Sciences

IDENTIFICATION TEST FOR ACTIVE INGREDIENT

1ml of 0.1 M HCl was added to 0.1g of paracetamol in a test tube and heated in a boiling
water bath for 3 minutes. 1 ml of distilled water was added and the contents of the test tube
allowed to cool in an ice bath. 0.05 ml of 4.9 g/l solution of potassium dichromate was added
and observed for color change. The production of a violet colour was considered a positive
test (BP, 2005).

WEIGHT UNIFORMITY
Twenty tablets of each brand were used. Each was weighed separately on an analytical
balance and the mean, standard deviation and percentage deviation calculated (BP, 2005).

HARDNESS TEST
The Monsanto hardness tester was used and the result expressed in Kg/F. Twenty tablets
were used for each sample. Each of the tablet was placed between the spindle and anvil, and
pressure applied by turning the knurled knob sufficiently to hold the tablet in position. The
reading of the pointer on the scale was then adjusted to zero. The pressure was then
increased as uniformly as possible as the tablet is crushed and the reading of the pressure
required to break the tablet noted. The hardness factor of each brand was the average of the
twenty factors for the twenty tablets.

FRIABILITY
The instrument used was a B and T DC – 01 tablet friability tester. Ten tablets randomly
chosen and previously weighed were placed in the hollow chamber. The instrument was
switched on and allowed to rotate for 4 minutes at 25 rpm (revolution per minute). The
tablets were removed, dusted and reweighed. The difference in weight was determined and
expressed in percentage.

DISINTEGRATION TIME TEST

The Avis disintegration single unit test apparatus was used with distilled water maintained at
37oC as the disintegrating fluid. Six tablets of each brand were used with each one placed in
each of the six baskets. The motor was switched on and the disintegrating time determined
with the use of a stop watch. The disintegrating time was the time taken when no particle of
the tablets remained in the No. 10 mesh baskets. The mean disintegration time for each of
the six tablets was determined (BP, 2005).

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Awemu et al. World Journal of Pharmacy and Pharmaceutical Sciences

DISSOLUTION RATE TEST

The Avis dissolution single unit test apparatus containing 900 ml of phosphate buffer (pH
5.8) maintained at 37oC was used. The process was done at a speed of 50 rpm. 5 ml aliquots
of the sample was withdrawn from the beaker and immediately replaced with 5 ml of
phosphate buffer (pH 5.8) at a regular time interval. A 1 ml of the aliquot withdrawn was
diluted to 10 ml and the absorbance taken. The percentage (%) drug release was calculated
(BP, 2005). The same procedure was carried out on the other samples.

CONTENT OF ACTIVE INGREDIENT

Twenty tablets of each sample were weighed, powdered and a quantity of the powder
containing 0.15 g of paracetamol was added to 50 ml of 0.1 M NaOH in a 200 ml volumetric
flask. 100 ml of water was added and the flask shaken for 15 minutes and the volume finally
made up to the 200 ml mark with water. The contents of the flask were mixed and then
filtered and 10 ml of the filtrate was diluted to 100 ml with water. 10 ml of the resulting
solution was added to 10 ml of 0.1 M NaOH and diluted to 100 ml with water. The
absorbance of the resulting solution was measured at 257 nm and the content of paracetamol
calculated by taking 715 as the value of A(1%, 1cm) at the maximum at 257 nm (BP, 2005).

RESULTS
All the 20 samples of paracetamol tablets involved in the study were well within shelf life at
the time the study was done. Three samples (15 %) of the drugs had no manufacturing dates
while one sample (5 %) had no expiry date. Two samples (10 %) had no NAFDAC
registration status (Table 1). All the drug samples had uniform organoleptic properties in line
with the BP specifications (Table 2). All the drug samples were evenly coloured, smooth,
tasted bitter and were odourless irrespective of their shape.

Table 2. Organoleptic properties of paracetamol tablets

Drug code Shape Colour Taste Texture Smell
PA1 Round White Bitter Smooth Odourless
PA2 Round White Bitter Smooth Odourless
PA3 Round White Bitter Smooth Odourless
PA4 Round White Bitter Smooth Odourless
PA5 Ovoid White Bitter Smooth Odourless
PA6 Round White Bitter Smooth Odourless
PA7 Ovoid White Bitter Smooth Odourless
PA8 Ovoid White Bitter Smooth Odourless
PA9 Round White Bitter Smooth Odourless
PA10 Round White Bitter Smooth Odourless

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Awemu et al. World Journal of Pharmacy and Pharmaceutical Sciences

PA11 Ovoid White Bitter Smooth Odourless

PA12 Ovoid White Bitter Smooth Odourless
PA13 Round White Bitter Smooth Odourless
PA14 Round White Bitter Smooth Odourless
PA15 Round White Bitter Smooth Odourless
PA16 Ovoid White Bitter Smooth Odourless
PA17 Round White Bitter Smooth Odourless
PA18 Round White Bitter Smooth Odourless
PA19 Round White Bitter Smooth Odourless
PA20 Round White Bitter Smooth Odourless

Furthermore they all gave positive colour tests indicating that they contained the active
ingredient (paracetamol) qualitatively. Results of the physicochemical evaluation of the drug
samples under study are shown in table 3.

Table 3. Physicochemical properties of paracetamol tablets

Drug WU Hardness Friability DT DR Assay
code (%) (Kg/f) (%) (mins) (mins) (%)
PA1 100 8.75 0.50 5 80 99.42
PA2 100 6.05 0.30 29 - 102.00
PA3 100 6.15 0.30 5 77 101.10
PA4 100 13.50 0.90 11 53 99.50
PA5 100 9.10 0.10 2 82 101.20
PA6 100 4.15 3.00 53 - 100.20
PA7 100 10.70 0.10 1 91 102.51
PA8 100 10.40 0.10 3 75 100.20
PA9 100 4.95 3.70 8 66 103.20
PA10 100 8.30 0.10 39 - 101.10
PA11 100 6.35 0.60 13 64 101.50
PA12 100 5.35 3.90 6 52 99.20
PA13 100 9.75 0.30 12 37 100.10
PA14 100 8.90 0.60 11 53 103.50
PA15 100 10.20 0.20 3 34 101.40
PA16 100 11.15 0.00 6 45 100.80
PA17 100 9.20 2.50 44 - 100.90
PA18 100 4.15 4.15 13 54 99.80
PA19 100 6.95 6.95 50 - 102.70
PA20 100 7.10 7.10 21 - 100.10
WU = Weight uniformity DT = Disintegration time DR = Dissolution rate

All the drug samples passed the weight uniformity and hardness tests. The disintegration
time for the tablets ranged from 1 to 53 minutes. 6 out of the 20 samples (PA2, PA6, PA10,
PA17, PA19 and PA20) failed the disintegration time test and were not involved in the
dissolution test. The highest disintegration time (53 min) was recorded for sample PA6 while

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sample PA7 had the lowest disintegration time of 1 minute. The acceptable percentage
dissolution within 45 minutes ranged from 90.50 to 102.50 % which is within the normal
range as stipulated by the British Pharmacopoeia (BP, 2005).

DISCUSSION
The quality of health care delivery is heavily dependent on the quality of pharmaceutical
products and the availability of qualified healthcare providers. In this study, samples of
paracetamol tablets were purchased without prescription from three major Nigerian cities of
Abuja, Benin and Onitsha. The parameters evaluated included; organoleptic properties,
weight uniformity, hardness/crushing strength, friability, disintegration time, dissolution rate
and percentage drug content. All the samples were tested qualitatively for the presence of the
active ingredient and the results were positive for all the samples. Colour tests should be the
first port of call during quality control testing of pharmaceutical drugs as they are fast and
require very basic instruments. All the paracetamol samples passed the uniformity of weight
test. The uniformity of weight test is one way of determining whether proper mixing or
blending of ingredients occurred during manufacturee. Also, even distribution of active
ingredient is necessary in order to avoid overdosing or underdosing which can both be fatal to
the patient (El-Duah, 2011). Although there is no official test for hardness, this property
must be controlled to ensure that the product is firm enough to withstand handling without
breaking or crumbling and not so hard that disintegration is unduly prolonged (Gomel,
2000). The hardness value for all the samples were greater than 4 kg/f, which is considered
the minimum for a satisfactory tablet (King and Schwartz, 1985). Excessive hardness of
tablets would prolong disintegration time thereby affecting dissolution, absorption and
bioavailability of the drug (Ogah et al., 2007). While soft tablets are not of sufficient
mechanical strength to withstand fracture and erosion during handling at all stages (Alderbon,
2007). 7 samples (PA6, PA9, PA12, PA17, PA18, PA19 and PA20) did not comply with the
BP specification of not more than 1% friability probably due to formulation factors such as
inadequate binders, high content of lubricants and disintegrants; and low moisture content.
Friability value of less than 1% is necessary to enable the tablets to withstand abrasion during
packaging and transportation without undue loss to tablet material (Ogah et al., 2007). 6
samples failed the disintegration time test as it took more than 15 minutes to disintegrate.

Prolonged disintegration time may be caused by factors such as use of excessive amount of
binders, high compression pressure, inadequate disintegrants or low concentration of

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lubricants (Ogah et al., 2007). Prolonged disintegration delays dissolution and slows down
the absorption of the active ingredient. All the paracetamol samples used in the study
complied with the BP specification of 95 – 105% drug content. This indicates that
NAFDAC’s efforts to ensure compliance with Good Manufacturing Practice (GMP) by local
pharmaceutical manufacturers is yielding fruits. The content of active ingredient is a very
important parameter in quality control because the therapeutic effectiveness of a drug is
dependent on the correct amount of active ingredient in the dosage form. Results of this
study clearly show that the efforts of NAFDAC towards ensuring that good quality drugs are
used in the Nigerian healthcare system are bearing fruits.

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