Journal of Applied Pharmaceutical Research ISSN No. 2348 ± 0335 www.japtronline.

com

FORMULATION AND CHARACTERIZATION OF CHEWABLE TABLETS OF

PARACETAMOL AND METOCLOPRAMIDE HYDROCHLORIDE
D Kumar*, D S Goswami, P Tomar, S Kaur
S. D. College of Pharmacy, Barnala, Punjab-148101

The present study was aimed to formulate and characterized chewable tablets of Paracetamol and
Metoclopramide hydrochloride. Paracetamol and Metoclopramide hydrochloride is an oral fixed dose
combination for the preparation of chewable tablets used to treat the symptoms of migraine as it comply with
physicochemical properties require to improve the effectiveness of therapeutic agent, better bioavailability,
improved patient acceptance (especially pediatrics) through pleasant taste, patient convenience; need no
water for swallowing, fasten the absorption of drug and for rapid onset of action. The investigation was
carried out to study the effect of different proportion of Avicel 101, Avicel 102 and moringa gum, which are
superdisintegrating agents. The chewable tablets of Paracetamol and Metoclopramide hydrochloride were
prepared by wet granulation method. Several physicochemical parameters like thickness, diameter, hardness,
%weight variation, %loss in weight, drug content, disintegration time, in vitro dissolution studies, kinetics of
drug release and stability studies for all the formulations were studied and were found within the acceptance
limits. Formulation F7 (containing moringa gum 1%) showed the best cumulative drug release and
disintegration time of 56 secs.
Key words: Paracetamol; Metoclopramide hydrochloride; chewable tablets Moringa gum.

INTRODUCTION formulation development involves the careful selection

Administration of drugs through oral route is the most of ingredients in order to manufacture a robust solid
common and the easiest way to administer a drug. dosage form. Choosing the appropriate excipients to
However, pediatric, geriatric and bedridden patient perform a specific function in a tablet formulation, such
shows inconvenience swallowing conventional tablets as disintegration or lubrication can be critical to
or capsules due to difficulties in swallowing with lesser achieving acceptable manufacturing performance.
amounts of water with the medication, unable to tolerate Sweeteners, both naturally occurring and synthetic, are
the taste of many drugs when formulated as liquid one type of functional excipients commonly used in
dosage forms, resulting in poor patient compliance. The chewable tablet formulations to mask unpleasant tastes
rationalized approach in case of medication leads to the and facilitate pediatric dosing.
development of chewable tablets. The advantages of Paracetamol and Metoclopramide hydrochloride is an
chewable tablet include palatability, stability, precise oral fixed dose combination for the preparation of
dosing, portability and ease of dosing.[1] chewable tablets used to treat the symptoms of migraine
Chewable tablets have been designed so that they may as it comply with physicochemical properties require to
be chewed in the mouth producing a pleasant tasting improve the effectiveness of therapeutic agent, better
residue in the oral cavity that is easily swallowed and bioavailability, improved patient acceptance (especially
does not leave a bitter a unpleasant taste. Chewable pediatrics) through pleasant taste, patient convenience;
tablets are the dosage forms, which are required to be need no water for swallowing, fasten the absorption of
broken and chewed in between the teeth before drug and for rapid onset of action.[2]
ingestion. These tablets are given to the children who
have difficulty in swallowing and to the adults who MATERIAL AND METHODS
dislike swallowing of drugs. Successfully tablet Metoclopramide hydrochloride, moringa gum,
tartrazine, aspartame and vanilla flavor were purchased
For Correspondence from Balaji drug, Gujrat,lactose, maize starch, citric
[email protected]

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acid, sodium starch glycolate, magnesium stearate and individually in order to achieve the desire drug release
talc were purchased from Central Drug House (P) Ltd. profile. Drug and other excepients were sieved and
New Delhi, Paracetamol, Avicel 101 and Avicel 102 mixed in a pestle and mortar. Maize starch and
were purchased from Sanjay Biological Museum, tartrazine (coloring agent) were dissolved in purified
Amritsar and mannitol was purchased from Rankem, water to get a starch paste. Drug mix was added to
New Delhi. starch paste and obtained wet mass, which was sieved
form # 10 mesh sieve. The obtained granules were
Preparation of chewable tablets containing dried in oven. After drying the granules were passed
Paracetamol and Metoclopramide hydrochloride: through # 16 mesh sieve. Then added magnesium
Chewable tablets containing 325 mg Paracetamol and stearate and talc as lubricant and glident and thoroughly
5mg Metoclopramide hydrochloride were prepared with blended for 3 mins. The tablets were compressed using
a total weight of 500 mg by wet granulation method of rotary punching machine using 11 mm punch.
different homogeneous blends containing Avicel 101, Compression force of machine was adjusted to obtain
Avicel 102 and moringa gum in different ratios the hardness for each formulation.[3-4]
Table:1 Formulation composition of chewable tablets containing Paracetamol & Metoclopramide hydrochloride
Ingredients Formulation code
F1 F2 F3 F4 F5 F6 F7 F8 F9
Paracetamol 325 325 325 325 325 325 325 325 325
Metoclopramide hydrochloride 5 5 5 5 5 5 5 5 5
Avicel 101 5 10 15 --- --- --- --- --- ---
Avicel 102 --- --- --- 5 10 15 --- --- ---
Moringa gum --- --- --- --- --- --- 5 10 15
Lactose 75 70 65 75 70 65 75 70 65
Mannitol 50 50 50 50 50 50 50 50 50
Maize starch 15 15 15 15 15 15 15 15 15
Citric acid 2 2 2 2 2 2 2 2 2
Sodium starch glycolate 3 3 3 3 3 3 3 3 3
Tartrazine 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5
Aspartame 10 10 10 10 10 10 10 10 10
Vanilla flavour 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5
Magnesium stearate 2 2 2 2 2 2 2 2 2
Talc 2 2 2 2 2 2 2 2 2
Purified water q.s q.s q.s q.s q.s q.s q.s q.s q.s

Evaluation of chewable tablets containing free standing surface of the powder heap and the
Paracetamol and Metoclopramide hydrochloride: h
horizontal plane.E = tanF1
r
Pre-Compression Parameters [5]
Determination of bulk density and tapped density
Angle of repose
A quantity of 5gm of the powder (W) from each
In order to determine the flow property, the angle of
formula was introduced into a 25 ml measuring
repose was determined using the standard procedure. It
cylinder. After the initial volume was observed, the
is the maximum angle that can be obtained between the
cylinder was allowed to fall under its own weight onto a
hard surface from the height of 2.5 cm at 2 sec intervals.

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The tapping was continued until no further change in % Minimum negative deviation = (A-WL/ A) x 100
volume was noted. The bulk density, and tapped density Where, WH = Highest weight in mg, WL=Lowest
were calculated using the following formulae - weight in mg, A= Average weight of tablet.
%XON GHQVLW\ : 9Ê Tapped density = W / Vf Drug content estimation
Where, W = weight of the powder, Vo = Initial volume, Five tablets were weighed individually and powdered.
Vf = Final volume The powder equivalent to average weight of the tablet
&RPSUHVVLELOLW\ LQGH[ &DUU¶V LQGH[ was weighed and drug was extracted in 0.1(N) HCl pH
It was identified using the formula, 1.2, the drug content was determined measuring the
C.I = 100 (V0 ± Vf) / V absorbance at 249 nm and 310 nm after suitable dilution
+DXVHU¶V 5DWLR using UV visible spectrophotometer.1
It indicates the flow properties of the powder and is Disintegration test
measured by the ratio of tapped density to the bulk Disintegration test was carried out by using
density. disintegration test apparatus. One tablet is placed in
+DXVHU¶V 5DWLR : 9f) / (W / V0) each tube, and the basket rack was positioned in a 1 ltr
Where, W / Vf= Tapped density, W / V0 =Bulk density beaker of water, at 37°C ±2°C. A standard motor-driven
device is used to move the basket assembly containing
Post compression parameters:[5--7] the tablets up and down through a distance of 5 to 6 cm
Shape of Tablets at a frequency of 28 to 32 cycles per mins. The time
The Compressed tablets were examined under the taken for the tablet to disintegrate completely was
magnifying lens for the shape of the tablet. noted.[7]
Tablet dimensions In vitro drug release study
Thickness and diameter were measured using a In vitro drug release studies were performed to provide
calliberated vernier caliper. Five tablets of each the amount of drug that is released at a definite time
formulation were taken randomly and thickness was period. In these release studies for all formulations were
measured individually. carried out using tablet dissolution USP type II (paddle
Hardness method). The dissolution media used was 0.1(N) HCl,
Hardness indicates the ability of a tablet to withstand pH 1.2 maintained at 37±0.50C and rotated 50 rpm.
mechanical shocks while handling. The hardness of the Aliquots were withdrawn at different time intervals and
tablet was determined using Monsanto hardness tester. the same volume of fresh medium was replaced to
It is expressed in kg/cm2. Five tablets were randomly maintain sink conditions. The samples were analysed
picked and hardness of the tablet was determined. DJDLQVW 1 +&O S+ DV EODQN DW PD[ QP
[8]
Friability Test and 310 nm using UV spectrophotometer.
The friability of tablets was determined using Roche
friabilator. It is expressed in percentage (%). Twenty RESULTS & DISCUSSION
tablets were initially weighed (w0 initial) and transferred The diameter of all formulations ranged between
into friabilator was operated at 25rpm for 4 mins or run 6.20±0.05 to 6.80±0.05 mm and thickness was in the
up to 100 revolutions. The tablets were weighed (w). range of 1.60±0.03 to 2.00±0.32 mm. All the batches
The friability was then calculated by showed hardness in the range 3.75±0.42 to 4.64±0.64
Friability = 100 (1-w/w0) Kg/cm2. The friability was found to be below 1%
Weight variation test ensuring that all the formulations were mechanically
Twenty tablets were selected at random and the average stable. Uniformity of weight and drug content was
weight was determined. evaluated usually by weight variation and content
% Maximum positive deviation = (WH ±A/ A) x 100 uniformity test. The variations in weight were within the

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range of -0.143±0.31 to 0.654±1.32% complying with Figure No-1 to 2. In the present study Paracetamol and
Pharmacopoeia specifications (±7.5 %). The range of Metoclopramide hydrochloride chewable tablet by wet
drug content for Paracetamol was 95.385±0.006 to granulation method using polymers like Avicel 101,
98.256±0.005% and for Metoclopramide hydrochloride Avicel 102 and moringa gum was developed.
was 95.319±0.020 to 99.574±0.032% for all Formulation F7 containing Moringa gum 5% showed
formulations. For all formulations disintegration time best cumulative drug release and disintegration time of
was in the range of 56±0.07 to 156±0.01 secs. The 56 secs, emerging as best formulation.
results were shown in Table No-5 to 6.
Table 3: Pre-formulation parameter of Metoclopramide
Table 2: Pre-formulation parameter of Paracetamol hydrochloride
Parameters Inference
Appearance White or almost white Parameters Inference
0
Melting point 169±1.15 C Appearance Ligh yellowish
Solubility In water Partially Soluble
Melting point 183±1.10°C
In methanol Freely Soluble
Solubility In Acetone Soluble
In Hcl Spraingly Soluble
In methanol Partially Soluble
Flow Angle of repose 25.25±0.02
properties In Hcl Soluble
Bulk density 0.5±0.02 gm/cc
Flow Angle of repose 27.85±0.05
Tapped density 0.66±0.02 gm/cc
properties Bulk density 0.45±0.02 gm/cc
&DUU¶V LQGH[ 24.24±0.05
Tapped density 0.62±0.04 gm/cc
+DXVQHU¶V UDWLR 1.32±0.01
&DUU¶V LQGH[ 23.20±0.03
Assay 98.4%
+DXVQHU¶V UDWLR 1.25±0.03
All the 9 formulations of prepared chewable tablets of Assay 99.5%
Paracetamol and Metoclopramide hydrochloride were
subjected to in vitro release studies. The results
obtaining in vitro release studies were plotted in
different model of data treatment. The release data
obtained for formulations F1 to F9 were showed in

Table 4: Flow properties of granules of formulations F1-F9

Formulation Bulk density* Tap density* &DUU¶ LQGH[* +DXVQHU¶V Angle of
Code (gm/cm3) (gm/cm3) (%) ratio* repose*
F1 0.50±0.03 0.50±0.01 6.25±1.04 1.07±0.05 27.54±0.89
F2 0.50±0.05 0.50±0.03 12.50±1.13 1.14±0.04 27.93±1.45
F3 0.53±0.04 0.53±0.02 6.67±0.97 1.07±0.07 28.46±1.32
F4 0.47±0.03 0.47±0.01 11.76±1.32 1.13±0.02 27.87±0.84
F5 0.43±0.05 0.43±0.02 16.22±0.87 1.19±0.03 26.55±0.62
F6 0.43±0.01 0.43±0.05 16.22±1.15 1.19±0.02 27.43±0.23
F7 0.53±0.01 0.53±0.02 10.00±0.20 1.11±0.02 27.48±1.20
F8 0.40±0.02 0.40±0.01 17.50±0.67 1.21±0.02 28.76±1.23
F9 0.40±0.03 0.40±0.03 15.00±0.35 1.18±0.07 28.32±0.87

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Table 5: Diameter, thickness, hardness and %loss in weight of formulation F1-F9

Batch Diameter* (mm) Thickness* (mm) Hardness* (kg/cm2) %Loss in wt.**
Code
F1 6.80±0.01 1.60±0.03 4±0.56 0.117±0.07
F2 6.20±0.05 1.80±0.06 4.32±0.14 0.056±0.04
F3 6.20±0.04 1.80±0.04 4.64±0.64 0.226±0.09
F4 6.40±0.01 2.00±0.32 4.62±0.87 0.423±0.17
F5 6.80±0.02 2.00±0.03 4.55±0.43 0.439±0.05
F6 6.80±0.05 1.80±0.22 3.75±0.42 0.2±0.18
F7 6.80±0.01 2.00±0.05 4.25±0.21 0.436±0.07
F8 6.80±0.04 2.20±0.16 4.52±055 0.112±0.03
F9 6.80±0.05 2.20±0.24 4.5±0.48 0.534±0.21

Table 6: %Weight variation, disintegration time, drug content of Paracetamol and drug content of
Metoclopramide of formulation F1-F9
Formulation %Weight Disintegration time Drug content** Drug content** of
Code variation** (in sec) of Paracetamol Metoclopramide
F1 -0.123±1.22 105±0.02 98.256±0.005 95.319±0.020
F2 0.235±1.56 90±0.01 96.821±0.010 97.872±0.005
F3 0.386±0.09 110±0.04 97.867±0.006 96.596±0.008
F4 0.256±1.24 145±0.05 96.205±0.007 99.574±0.032
F5 0.654±1.32 134±0.01 95.385±0.006 98.298±0.004
F6 -0.056±1.24 156±0.01 96.615±0.008 96.596±0.002
F7 0.116±1.52 56±0.07 95.795±0.007 95.787±0.008
F8 -0.143±0.31 62±0.01 96.615±0.017 96.340±0.003
F9 0.237±0.03 70±0.05 96.205±0.002 97.574±0.010
%Cumulative drug release

100 100
%Cumulative drug

80 80
release

60 60
40 40

20 20
0
0
0 0.5 1 1.5 2
0 0.5 1 1.5 2
F1 F2 (hrs) F3 F1 Time (hrs) F3
F2
Time
F4 F5 F6 F4 F5 F6

Fig. 1: Comparison graph of in vitro drug release Fig. 2: Comparison graph of in vitro drug release
profile of formulations F1-F9 containing profile of formulations F1-F9 containing
Paracetamol Metoclopramide hydrochloride

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Accepted 14th Aug 2014
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