FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF AMLODIPINE BESILATE

1. Int. J. Pharm. Res. Sci., 2013, 01(1), 26-32.
ISSN: 2348 –0882
FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS
OF AMLODIPINE BESILATE.
Udgirkar D.B, Bhalsing M.D*, Rao K.S, Gawali V.B.
RRKS College of Pharmacy,Bidar,Karnatka, India
======================================================
ABSTRACT:
In the present study an attempt was made to
formulate
Orodispersible
tablets
of
amlodipine besilate with a view to provide a
convenient mean of administration to those
patients suffering from isolated systolic
hypertension and Angina. Orodispersible
tablets of Amlodipine Besilate using
different superdisintegrants were prepared
by direct compression method. The
Superdisintegrants used in this study were
Croscarmellose
sodium
(CCS),
Crospovidone (CP) and Sodium Starch
Glycolate (SSG) in varying concentrations
(4%, 6% & 8%). The prepared tablets were
evaluated for post compressional parameters
such as hardness, friability, thickness, invitro dispersion time, wetting time, and
water
absorption
ratio.
Effect
of
superdisintegrants [such as croscarmellose
sodium,
sodium
starch
glycolate,
crospovidone] on wetting time, in-vitro
dispersion time and stability parameter has
been studied. In-vitro dispersion time
decreases with increase in the concentration
of croscarmellose sodium and in-vitro
dispersion time increases with increase in
concentration of sodium starch glycolate.
However in-vitro dispersion time value did
not reflect major change with increase in the
concentration of crospovidone. The tablets
prepared by direct compression method
containing 8 % of croscarmellose sodium
showed highest in vitro drug release of
98.23 % within 30 min. From this study it is
concluded that Orodispersible tablets could
be prepared by direct compression method
using different superdisintegrants enhanced
dissolution will lead
to
improved
bioavailability, improved effectiveness of
Amlodipine besilate.
Keywords: Orodispersible tablets,
Amlodipine Besilate, Croscarmellose
sodium, Crospovidone and Sodium Starch
Glycolate
INTRODUCTION:
Amlodipine Besilate, is 3-Ethyl 5methyl 2- (2-aminomethoxymethyl) -4- (2chlorophenyl)-1,4-dihydro-6methylpyridine3, 5-dicarboxylate monobenzene sulphonate.
Calcium channel blocker used in treatment
Corresponding Author: Bhalsing MD
RRKS College of Pharmacy,Bidar,Karnatka,
India
Email: dattubu@yahoo.co.in
Received: 17.11.2013
Revised: 09.12.2013
Accepted: 16.12.2013
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2. Int. J. Pharm. Res. Sci., 2013, 01(1), 26-32.
ISSN: 2348 –0882
of hypertension and angina (chronic, stable
or vasopastic).1,2
Solid dosage forms like tablet and
capsule are most popular and preferred drug
delivery system because they have high
patient compliance, relatively easy to
produce, easy to market, accurate dosing,
and good physical and chemical stability.3
However, many patient groups such as the
elderly, children, and patients who are
mentally retarded, uncooperative, nauseated,
or on reduced liquid-intake/ diets have
difficulties swallowing these dosage forms.
Those who are traveling or have little access
to water are similarly affected.4 For these
reasons, tablets which can rapidly dissolve
or disintegrate in the oral cavity have
attracted a great deal of attention. Rapidly
dissolving or disintegrating tablets are not
only indicated for people who have
swallowing difficulties, but also are ideal for
active people.5
Many patient find difficulties to
swallow tablet and hard gelatin capsule,
consequently they do not take medication as
prescribed. It is estimated that 50% of the
population is affected
by this problem
which result high incident of incompliance
and ineffective therapy. 6 This disorder is
also associated with number of
medical
conditions including stroke, Parkinson’s
disease, AIDS, head and neck radiation
therapy and other neurological disorders
including cerebral palsy. Recent advances in
novel drug delivery system aim to enhance
safety and efficacy of drug molecule by
formulating a convenient dosage form for
better patient compliance.7
The growing importance of mouth
dissolving tablet was underlined recently
when European Pharmacopoeia adopted the
term “Orodispersible Tablet” as a tablet that
to be placed in the mouth where it disperses
rapidly before swallowing. Suitable drug
candidates for such systems include
neuroleptics,
cardiovascular
agents,
analgesics, antiallergics and drugs for
erectile dysfunction.8 To overcome this
weakness,
scientist
have
developed
innovative drug delivery system known as
fast dissolving “melt in mouth” or mouth
dissolve (MD) tablet. These are novel type
of tablet that disintegrate dissolve / disperse
in saliva.9
MATERIAL & METHODS:
Amlodipine besilate was obtained as
a gift sample from Emcure pharma. Ltd.,
Pune. croscarmellose sodium (CCS) &
crospovidone (CP) obtained as a gift sample
from cipla , sodium starch glycolate (SSG)
& aspartame procured from Himedia labs,
mumbai.
Directly
compressible
microcrystalline cellulose (MCC) and
mannitol (directly compressible) were
procured from SD fine chem. Other reagents
were of analytical grade.
Method:
Preparation of orodispersible tablets of
Amlodipine
besilate
by
direct
compression method:
Orodispersible tablets of Amlodipine
besilate
were
prepared
by
direct
compression. All the ingredients were
passed through 60-mesh separately. Then
the ingredients were weighed and mixed in
geometrical order and compressed into
tablets of 150mg using 8mm round flat
punches on multi station rotary punch tablet
compression machine. (Clit Pilot press
Chamnnda Gujarat) A batch of 30 tablets of
each formulation was prepared for all the
designed
formulations.
Different
formulations compositions are given in
(Table 1).
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3. Int. J. Pharm. Res. Sci., 2013, 01(1), 26-32.
ISSN: 2348 –0882
Table 1: Formulation of Amlodipine besilate orodispersible tablets prepared by direct
compression method
Formulation code
Ingredients (mg)
F1
F2
F3
F4
F5
F6
F7
F8
F9
Amlodipine besilate
10
10
10
10
10
10
10
10
10
MCC
80
80
80
80
80
80
80
80
80
41.3
38.3
35.3
41.3
38.3
35.3
41.3
38.3
35.3
Mannitol
CCS
6
9
12
-
-
-
-
-
-
SSG
-
-
-
6
9
12
-
-
-
CP
-
-
-
-
-
-
6
9
12
Aspartame
10
10
10
10
10
10
10
10
10
Mixed fruit flavor
1
1
1
1
1
1
1
1
1
Talc
1
1
1
1
1
1
1
1
1
Magnesium Sterate
0.70
0.70
0.70
0.70
0.70
0.70
0.70
0.70
0.70
Total weight
150
150
150
150
150
150
150
150
150
Table 2: Evaluation of tablets
Formula Average
Hardness
tion
weight*
*
Code
(kg/cm2)
Friabili
ty
(%)
Wetting
Time*
(sec)
Water
Invitro
absorpti Disintegratio
on ratio* nTime* (sec)
Drug
Conten
t (%)
F1
149  1.78
3.6  0.11
0.81
67  2.51
70  1.54
32  2.78
98.05
F2
148  1.32
3.7  0.11
0.64
65  2.0
72  1.86
31  1.0
96.11
F3
150  0.56
3.9  0.10
0.31
61  2.40
78  1.35
28  1.0
99.44
F4
149  1.97
3.7  0.12
0.62
76  1.89
56  1.58
48  2.0
96.94
F5
150  0.65
3.8  0.18
0.47
73  2.20
63  1.21
50  1.5
97.50
F6
150  1.93
3.6  0.10
0.65
69  1.0
68  1.57
53  1.7
96.66
F7
149  1.21
3.7  0.15
0.82
69  2.25
63  1.20
38  2.8
99.16
F8
149  1.50
3.6  0.21
0.80
67  2.15
68  1.05
35 1.45
98.88
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4. Int. J. Pharm. Res. Sci., 2013, 01(1), 26-32.
F9
151  0.18
ISSN: 2348 –0882
3.9  0.10
65  1.0
0.64
71  1.73
97.22
34 1.28
% Drug Release
* Average of three determinations.
120
100
80
60
40
20
0
F1
F2
F3
0
10
20
30
40
Time in min.
Fig 1: Release profile of Amlodipine besilate tablets containing croscarmellose sodium
% Drug Release
120
100
80
60
F4
40
F5
20
F6
0
0
10
20
30
40
Time in min.
Fig 2: Release profile of Amlodipine besilate tablets containing sodium starch glycolate.
120
% Drug Release
100
80
60
F7
40
F8
20
F9
0
0
5
10
15
20
Time in min.
29
25
30
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5. Int. J. Pharm. Res. Sci., 2013, 01(1), 26-32.
ISSN: 2348 –0882
Fig 3: Release profile of Amlodipine besilate tablets containing crospovidone.
Wb is weight of tablet after water
absorption.
The results are shown in Table 2.
5. In-vitro disintegration time:12 One tablet
each was placed in each of the six tubes
basket. Add a disc to each tube and run the
apparatus using pH 7.4 maintained at
37±2C as the immersion liquid. The
assembly should be raised and lowered
between 30 cycles per minute in the pH 7.4
maintained at 37±2C. The time in seconds
taken for complete disintegration of the
tablet with no palpable mass remaining in
the apparatus was measured and recorded.
6. Dissolution Studies:13 Dissolution rate
was studied by using USP type-II apparatus
(USP XXIII Dissolution Test Apparatus at
50 rpm) using 900ml of phosphate buffer pH
(7.4) as dissolution medium. Temperature of
the dissolution medium was maintained at
370.5°C, aliquot of dissolution medium
was withdrawn at every 5 min interval and
filtered. The absorbance of filtered solution
was measured by UV spectrophotometric
method at 237.5 nm and concentration of the
drug was determined from standard
calibration curve.
Evaluation of Amlodipine besilate
Orodispersible tablets:
1. Average Weight :10 Twenty tablets were
selected at a random and average weight
was calculated. Then individual tablets were
weighed and the individual weight was
compared with an average weight.
2. Hardness and Friability:10 Tablets were
evaluated for hardness and friability test
using Monsanto hardness tester and Roche
friabilator respectively. The percentage
friability was then calculated by,
Winitial - Wfinal
x100
F=
Winitial
3. Content uniformity test:11 Four tablets
weighted and crushed in a mortar then
weighed powder contain equivalent to 10
mg of drug was taken and dissolved in 100
ml methanol, from this solution 1 ml of
solution was diluted to 10 ml methanol
again 1 ml solution from this diluted upto 10
ml with methanol
and assayed for drug
content at 237.5 nm
4. Wetting Time and water absorption
ratio:10 Wetting time and water absorption
ratio is intimately related to the
hydrophilicity of the excipient and to the
pore size of tablets. A piece of tissue paper
folded twice was placed in a small Petri‐dish
(internal diameter of 6.5 cm) containing 10
ml of water. A tablet was placed on the
paper and the time required for complete
wetting was measured. The wetted tablet
was then weighed. Water absorption ratio
‘R’ was determined using the equation,
R=100{(Wa‐Wa)/Wa}
Where, Wa is weight of tablet before water
absorption,
RESULTS AND DISCUSSION
In this study total nine formulation of
amlodipine orodispersible tablets were
formulated direct compression technique
using croscarmllose sodium, Crospovidone
and
Sodium
starch
glycolate
as
superdisntegrants. The post‐compression
parameters such as hardness, friability,
weight variation, amount of drug content;
in‐vitro wetting time and in‐vitro
disintegration time were evaluated which are
shown in table 2.
1. Average Weight: The weight variation of
all the tablets tested was within the
pharmacopoeial limits. The weights of
tablets of various batches were between 148151 mg.
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6. Int. J. Pharm. Res. Sci., 2013, 01(1), 26-32.
ISSN: 2348 –0882
2. Hardness and Friability: It is well
known that the hardness of the tablet can
markedly affect the release rate of drug. The
hardness was found to be in the range of
3.10 to 3.90 kg/cm2. It indicates good
mechanical strength with a capability to
resist physical and perfunctory stress
conditions during handling.The friability
values of all the formulations are less than
1% and they meet the pharmacopoeial
standards
3. Content uniformity test:. The
percentages drug contents of all the tablets
were found to be between 96.11 to 99.44
which was within the acceptable limits as
mentioned for normal amlodipine tablets
mentioned in USP
4. Wetting Time and water absorption
ratio: The results of in‐vitro wetting time
and water absorption ratio were found to be
within the prescribe limits and satisfy the
criteria of orodispersible tablets. Wetting
time for all formulation batches prepared by
direct compression method showed wide
variation in the range of 61 and 76 seconds.
This wide variation range was observed due
to developmental changes in formulation.
Wetting time for all
these
formulation batches varied in the following
increasing order: Croscarmellose sodium <
Crospovidone < Sodium starch glycolate.
The formulations prepared by direct
compression
technique
shows
water
absorption ratio in the range 56 to 78 %
formulations containing only 4% of
superdisintegrant shows lower water
absorption ratio when compared to
formulations 8% of superdisintegrant, the
water absorption ratio also decreases due to
less swelling property. It was observed that
as concentrations of CCS increases water
absorption ratio increases due to CCS is
made by cross- linking reaction of sodium
CMC. This cross linking greatly reduced
water solubility of sodium CMC while
permitting material to swell and absorbs
water many times of its weight.
5. Invitro disintegration time: The
formulation showed ideal characteristic of a
dispersible type tablet. The rate of
disintegration of formulations increased with
variation in concentration of various
disintegrants. Batch F3, containing a higher
amount
of
croscarmellose
sodium,
disintegrates rapidly than other batches and
showed increased disintegration time.
6. Dissolution Studies: The invitro
dissolution profile indicate the faster and
maximum of 97.56 % drug release within 30
min from formulation F3 proving the
disintegrating property of Croscarmellose
sodium. It was observed that when
preparation
containing
Croscarmellose
sodium comes in contact with water, it gets
exaggerated immediately causing a quick
rupture there by releasing the entire drug
within the small time lap. The utmost raise
in the dissolution rate with various
superdisintegrants was found to be
Croscarmellose sodium> Crospovidone >
SSG shown in fig1, 2, 3.
CONCLUSION
In the present study the disintegrating
properties of the croscarmellose sodium,
Crospovidone and Sodium starch glycolate
had been studied. All the disintegrants
showed a rapidly disintegration, which is
required for faster drug dissolution and
improved bioavailability. Croscarmellose
sodium has the lead over others, thus
proving its future prospects as a
superdisntegrants in orodispersible tablets
for rapid absorption, effective therapy and
patient compliance. The batch F3 containing
croscarmellose sodium 8% was found to be
the best as compare to other formulations as
this formulation has optimum hardness (3.9
kg/cm2), friability (0.31), wetting time (61
sec.) and disintegration time of (28 sec). By
an appropriate combination of excipients it
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7. Int. J. Pharm. Res. Sci., 2013, 01(1), 26-32.
ISSN: 2348 –0882
was thus possible to obtain orally
disintegrating tablets of Amlodipine besilate
using simple and conventional techniques.
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