Research J. Pharm. and Tech. 1(4): Oct.-Dec.

2008,

www.rjptonline.org

ISSN 0974-3618
RESEARCH ARTICLE

Formulation and Evaluation of Effervescent Floating Tablet of Amlodipine

besylate
Pare A, Yadav SK and Patil UK*
V N S Institute of Pharmacy, V N S Campus, Vidya Vihar, Barkheda Nathu, Neelbud, Bhopal (M P)-462044
* Corresponding Author E-mail: umeshpatil29@yahoo.com

ABSTRACT
Amlodipine besylate effervescent floating tablets were developed in ten different formulations (F1 to F10) by employing
different grades of polymers and effervescent agents such as sodium bicarbonate and citric acid. The formulations were
evaluated for various physical parameters, buoyancy studies, dissolution parameters and drug released mechanisms. F10
formulation showed maximum floating time of 24 hours and gave slow and maximum drug release of Amlodipine
besylate spread over 24 hours and whereas Amlodipine besylate released from marketed tablet was rapid and maximum
within 12 hours.

KEY WORDS

Amlodipine besylate, Effervescent floating tablet.

INTRODUCTION:

EXPERIMENTAL

Effervescent floating drug delivery systems generate

gas (CO2), thus reduce the density of the system and
remain buoyant in the stomach for a prolonged period
of time and released the drug slowly at a desired
rate.1,2,3 Amlodipine is long acting calcium channel
blocker and used in the treatment of hypertension, and
chronic stable angina. In hypertension or angina,
initially 5 mg. one daily and adjusted to maximum dose
10 mg one daily dose of Amlodipine is given orally.4
Amlodipine has maximum solubility in acidic pH.
Amlodipine has some adverse effect such as nausea,
abdominal pain. Effervescent floating tablet of
Amlodipine besylate retain in stomach improves
solubility, bioavailability, reduces drug waste and
decrease side effect such as gastric irritation and
nausea.5, 6

Materials
Amlodipine besylate was procured from Signa Pharma Pvt.
Ltd. Kanpur. HPMC K100 M, HPMC K15 M, Carbapol 934
p, Sodium biacarbonate, Citric acid, poly vinyl pyrrolidine
and Talc were obtained from Colorcon Asia Pvt. Ltd and
Loba chemicals. Amlosafe 10 (marketed brand of
Amlodipine besylate) tablets were purchased from local
market.

In present work, effervescent floating tablets of

different formulation were developed with an objective
of achieving 24 hrs floating and drug release time and
the effervescent floating tablet was compared with
marketed formulation of Amlodipine besylate for drug
released time.

Received on 20.07.2008
Accepted on 25.08.2008

Modified on 23.08.2008
RJPT All right reserved

Methods
Effervescent Floating tablets containing Amlodipine
besylate were prepared by direct compression technique
using varying concentrations of different grades of polymers
with Sodium bicarbonate and citric acid. All the ingredients
were accurately weighed and passed through different mesh
sieves accordingly. Then, except Magnesium stearate all
other ingredients were blended uniformly in glass mortar
After sufficient mixing of drug as well as other components,
Magnesium stearate was added, as post lubricant, and further
mixed for additional 2-3 minutes. The tablets were
compressed using rotary tablet machine. The weights of the
tablets were kept constant for all formulation.
Evaluation of effervescent floating tablet formulations
Hardness of the tablets was tested using a Monosanto
hardness tester. Friability of tablets was determined in Roche
friabilator. Ten tablets were selected randomly from each
batch and weighed individually to check for weight
variation. The results are given in table no. 2

Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008;Page 526-530

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Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008,

First Order Release Kinetics

120
F1
F2
F3
F4
F5
F6
F7
F8
F9

100
80
60
40
20

Log Cumulative % Drug

Retained

Cumulative % Drug Release

Invitro Dissolution Release

2.5

y = -0.0729x + 2.0996
R2 = 0.9475

2
1.5
1
0.5
0
0

10

15

20

25

30

Time (hrs)
0

10

15

20

25

30

Log Cum % Drug Retained

Time(hrs)

Linear (Log Cum % Drug Retained)

Figure 4: Plot of log cumulative percentage drug retained vs.

time of optimized formulation (F10) [First order]

Figure 1: In-vitro dissolution profile of formulations F 1 to F 9

Invitro Dissolution Data

Higuchi Release Mechanism

100

120
Cumulative % Drug Release

Cumulative % Drug Release

120

80
60
40

F10

20
0
0

10

15

20

25

30

y = 23.761x - 12.922
R2 = 0.9924

100
80
60
40
20
0

Time (Hrs)

Root Of Time

Figure 2: In-vitro dissolution profile of optimized

formulation (F 10)

cumulative % drug release

Figure 5: Plot of cumulative percentage drug released vs.

root time of optimized Formulation (F10) [Higuchi Matrix]

Zero Order Relaese Kinetics

120

Korsmeyer & Peppas Release Mechanism

100
80
y = 4.2369x + 11.403
2
R = 0.9528

60
40
20
0
0

10

Cum % Release

15

20

25

Linear (Cum % Release)

30

Log Cumulative % Drug

Released

Cumulative % Drug Release

Linear Cumulative % drug release

y = 0.6901x + 1.0848
R2 = 0.9959

2.5
2
1.5
1
0.5
0
0

0.5

Time (hrs.)
Log Cum % Drug Release

Figure 3: Plot of cumulative percentage drug released

vs. time of optimized formulation (F10) [Zero Order]

The buoyancy lag time (BLT) and total floating time (TFT)7
On immersion of tablets of different formulations in
0.1N HCl solution at 375C, the tablets floated, and
remained buoyant without disintegration, the results of
the buoyancy lag time (BLT) and total floating time
(TFT) were shown in Table 3.
Estimation of Amlodipine besylate8
Amlodipine besylate content in the tablets was
estimated by using UV spectrophotometric method
based on the measurement of absorbance at max 239

1.5

Log Time
Linear (Log Cum % Drug Release)

Figure 6: Plot of log cumulative percentage drug released vs.

log time of optimized formulation (F10) [Korsmeyer and
Peppas Model]

nm in phosphate buffer 7.4. Amlodipine besylate content of

the tablets are given in Table 4.
Drug release study
In vitro release studies of F1 to F10 formulations and one
brand of Amlodipine besylate were carried out in the
dissolution test apparatus (USP Type II). The tests were
carried out in 900 ml of dissolution media 7.4 pH buffers for
24 hrs at 50 rpm at 370.5C 10 ml of the aliquot were
withdrawn at different predetermined time intervals (0.5, 1,

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Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008,

Table 2: Hardness, Friability, Weight variation of tablets

of different formulation F1 to F10
Formulation
Hardness
Friabilit Weight
(Kg/cm2)
y (%)
Variation (mg)
F1
0.96
4.5 0.47
3345%
F2
0.72
4.4 0.32
3315%
F3
0.91
4.4 0.54
3285%
F4
0.86
4.3 0.42
3295%
F5
0.79
4.5 0.35
3275%
F6
0.97
4.5 0.54
3345%
F7
0.72
4.5 0.54
3335%
F8
0.72
4.3 0.42
3275%
F9
0.72
4.4 0.32
3325%
F10
0.86
4.4 0.32
3295%
*Values are mean S.D

2, 4, 6, 8, 10, 12, 16, 20, 24 hr) and filtered. The

required dilutions were made with and the solution was
analyzed for the drug content by using UV detector
detecting at max 239 nm 10 ml of sample was replaced
in the vessel after each withdrawal to maintain sink
condition. From this percentage drug release was
calculated and this was plotted against function of time
to study the pattern of drug release. The in-vitro drug
release profiles of tablet from each batch (F1 to F10)
were shown in Table 5. The plot of cumulative
percentage drug release versus time (hr) was plotted
and depicted as shown in Figure 1 and 2
Analysis of release mechanism
In order to examine the release mechanism of
Amlodipine besylate from the prepared floating tablets
of the optimized formulation (F10), the results of the
dissolution study was examined in accordance to the
kinetic models. The regression coefficient R2 value
nearer to 1 indicated the model fitting of the release
mechanism. The results are shown in Table 6 and
Figure 3 to 6.
Comparison with marketed product:
The promising formulation (F10) as found by
evaluation studies was compared with marketed
product Amlosafe (Amlodipine besylate). The
evaluation parameters tested and compared were drug

F4
10
50
100
--50
60
30
10
10
5
5
330

F5
10
--100
50
50
60
30
10
10
5
5
330

F6
10
100
--50
50
60
30
10
10
5
5
330

F7
10
100
50
--50
60
30
10
10
5
5
330

F8
10
100
50
50
--60
30
10
10
5
5
330

F9
10
110
40
50
--60
30
10
10
5
5
330

F10
10
125
40
40
--60
30
10
5
5
5
330

content uniformity and in-vitro dissolution profile. The

values of comparative in-vitro dissolution study of optimized
formulation (F10) and marketed product are recorded in
Table 7 and the result had come that the F10 formulation
was sustained released as compare with Amlosafe tablet.

Comparative Invitro Dissolution Drug Released

120
Cumulative % D rug
Released

Table 1: Composition of all the Formulations (F1 F10)

Ingredient
F1
F2
F3
Amlodipine
10
10
10
HPMC K100M
--100
--HPMC K15M
100
----Carbopol 934P
----100
MCC
100
100
100
Sodium Bicarbonate
60
60
60
Citric Acid
30
30
30
Poly vinyl Pyrrolidine K30
10
10
10
Magnesium Stearate
10
10
10
Talc
5
5
5
Aerosil
5
5
5
330
330
330
Total weight
*All the quantities are in mg

100
80
60
40

F 10

20

Marketed Product

0
0

10

Time (hrs)

20

30

Figure 7: Plot of Comparative dissolution profile of optimized

formulation (F10)
and marked product

RESULTS AND DISCUSSION:

Amlodipine is a potent drug for the treatment of angina,
hypertension and also suitable in the treatment diabetic
hypertension. Amlodipine had maximum solubility in acidic
pH. Amlodipine has some adverse effect such as headache,
nausea, abdominal pain. Prolonged gastric retention
improves bioavailability, reduces drug waste and improves
solubility for drugs that are less soluble in high pH
environment.
Effervescence production, decrease the
several local GIT side effect, such as gastric irritation,
nausea and gastritis.
The effervescent floating tablets of Amlodipine besylate
were formulated in ten different batches F1 toF10 by using
hydrophilic polymers HPMC K100M, HPMC K15M and
hydrophobic polymer carbopol 934P along with effervescing
agent sodium bicarbonate and citric acid. It was found that
carbopol has a negative effect on floating behavior but it was
used only for the drug release retardant characteristics. All
the formulations were prepared by direct compression

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Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008,

method. The prepared tablets of all the formulations

were evaluated for physical characters like tablet
hardness, friability, weight variation buoyancy lag
time, total floating time, assay, in-vitro drug release.
The main aim was to optimize the formulation for 24
hours in-vitro release and total floating time to more
than 24 hours.
Table 3: Buoyancy Lag Time, Total Floating Time of
formulations (F1toF10)
Formulation
Buoyancy
Lag Total
Floating
Time (Sec)
Time (hrs)
F1
133 sec
>12 hrs
F2
130 sec
>14 hrs
F3
Fail
Fail
F4
120 sec
>16 hrs
F5
102 sec
>16 hrs
F6
150sec
>20hrs
F7
140sec
>20hrs
F8
141sec
>24hrs
F9
138sec
>24hrs
F10
110sec
>24hrs

The measured hardness of tablets of each formulation

ranged between 4.1 to 4.5 kg/cm2. The % friability was
less than 1% in all the formulations ensuring that the
tablets were mechanically stable. All the tablets passed
weight variation test as the % weight variation was
within the Pharmacopoeial limits of 5% of the weight.
Buoyancy lag time (BLT) and total floating time (TFT)
of different formulation were noted, where F1 BLT of
133 sec and TFT of >12 hours, F2 BLT of 130 sec and
TFT of >14 hours, F3 fails to buoyancy because of
absence of H P M C polymers, F4 BLT of 120sec and
TFT of >16 hours, F5 BLT of 102 sec and TFT of >16
hours, F6 BLT of 150 sec and TFT of >20 hours, F7
BLT of 140 sec and TFT of >20 hours, F8 BLT of 141
sec and TFT of >24 hours, F9 BLT of 138 sec and TFT
of >24 hours, F10 BLT of 110 sec and TFT of >24
hours, With reference to buoyancy studies results it can
be concluded that the batch containing HPMC
polymers showed good buoyancy lag time (BLT) and
total floating time (TFT). Formulation F10 containing
HPMC K15M, HPMC K100M and carbopol 934P
showed good BLT of 110 sec and TFT of more than 24
hrs.
Amlodipine besylate release from the effervescent
floating tablets was studied in phosphate buffer pH 7.4.
The release profile of various formulations are shown
in table no. Figure no. 1 and 2. Formulation F1 released
98.4% of the drug in 12 hours. Formulation F2 released
98.4% of the drug in 16 hours. Formulation F3 released
96.2% of the drug in 8 hours. Formulation F4 released
98.3% of the drug in 16 hours Formulation F5 released
98.7% of the drug in 16 hours Formulation F6 released
98.4% of the drug in 16hours.Formulation F7 released
98.3% of the drug in 16 hours. Formulation F8 released

98.8% of the drug in 20 hours. Formulation F9 released

98.4% of the drug in 20 hours. F10 released 98.6 % of drug
in 24 hours. Thus F10 formulation was said to be optimized
formulation.
Table 4: Drug
F10
Batches
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10

Content Uniformity of Tablets of Batch F1 to

Drug content uniformity (%)
97.01
99.51
98.01
97.42
98.41
99.05
99.05
98.46
98.45
99.82

Optimized formulation F10 was subjected to curve fitting

analysis, zero order, and first order, Higuhi Kinetics,
Korsmeyer and Peppas model. The slope and r2 are shown in
Table 6 and graphs in Figure 3 to 6. Optimized formulation
F10 fitted best for Korsemeyer Peppas equation with R2
value of 0.9959.
Comparison study with marketed product of Amlodipine
besylate10mg (Amlodipine 10) showed that the optimized
formulation F10 has better control over release rate in
comparison to the commercial product. The marketed
product released the drug 98.3% in 12 hours whereas the
optimized formulation F10 released the drug 72.1% in 12hrs.
And the optimized formulation F10 remained floatable in the
stomach for 24 hours .and give the maximum released 98.6
at 24th hours.
It is, thus concluded that effervescent floating tablet
containing Amlodipine besylate (F10 formulation) gave
slow and complete drug release spread over 24 hours.

ACKNOWLEDGMENT:
The authors are grateful to Centre for development action
and community research (CDACR) for help in literature
survey and procurement of drug sample.

REFERENCES:
1. Deshpande AA, Shah NH, Rhodes CT and Malick W.
Development of a novel controlled release system for gastric
retention. Pharm. Res. 1997; 14(6): 815-819.
2. Klausner EA, Lavy E, Friedman M and Hoffman A. Expandable
gastroretentive dosage form. J. Control. Rel. 2003; 90: 143-162.
3. Singh BN and Kim HK. Floating drug delivery systems: an
approach to oral controlled drug delivery via gastric retention. J.
Control. Rel. 2000; 63: 235-59.
4. Barar FSK. Essentials of pharmacotherapeutis.3rd S. Chand and
Company Ltd. New Delhi. 246
5. Gutierrez-rocca J, Omidian H and Shah K. Progress in
Gastroretentive Drug Delivery System Bussiness Briefing,
Pharmatech. 2003: 152-156.

529

Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008,

Table 5: In-vitro drug release profile of tablets of F1 to F10

Time
(hr)
0.5
1.0
2.0
3.0
4.0
6.0
8.0
12.0
16.0
20.0
24.0

Cumulative Percentage Drug Release

F1
F2
F3
F4
18.5
15.8
20.2
15.3
30.2
27.3
32.5
26.8
42.8
39.8
45.2
37.1
55.2
51.5
57.3
49.9
68.5
61.9
69.8
60.8
76.8
72.7
88.5
71.8
89.6
81.5
96.2
83.1
98.4
96.2
93.2
98.4
98.3

F5
13.5
28.2
39.8
51.5
62.9
73.7
84.9
95.3
98.7

F6
12.8
27.4
38.3
50.2
61.1
72.4
84.1
94.5
98.4

F7
13.6
22.3
35.2
48.4
59.2
69.3
78.8
89.2
98.3

F8
10.7
15.8
24.6
32.4
42.7
55.2
70.8
84.7
96.2
98.8

F9
10.2
16.1
23.5
30.3
41.6
53.1
68.7
79.8
95.5
98.9

F10
7.3
11.7
19.4
25.9
32.1
43.2
52.8
72.1
85.8
96.8
98.6

Table 6: Kinetic Release Data of Different Model for

Optimized Formulation (F10)
Model
Zero order
First order
Higuchi
Korsemeyer-Peppas model

Slope
4.2369
-0.729
23.761
0.6901

R2value
0.9528
0.9475
0.9924
0.9959

Table 7: Comparative dissolution profile of optimized

formulation (F10) and marketed product.
Time (hr)
Cumulative percentage drug release
F10
Marketed product
0.5
7.3
15
1.0
11.7
25.01
2.0
19.4
40.3
3.0
25.9
65.42
4.0
32.1
66.04
6.0
43.2
70.8
8.0
52.8
92.0
12.0
72.1
98.3
16.0
85.8
20.0
96.8
24.0
98.6
-

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530