72 International Journal of Pharmacy and Pharmaceutical Science Research 2013; 3(2): 72-78
ISSN: 2249-0337
Original Article
Formulation, Optimization and Evaluation of Bi-layer Immediate release tablets
of Telmisartan and Amlodipine Besilate using full factorial design
Soham Shukla1*, Vikram Pandya
1, Praful Bharadia
1, Shashank Mishra
2, Deepak Bhatt
2, Nitin Jonwal
2
1B. S. Patel Pharmacy College, Gujarat, India
2 Cadila Pharmaceuticals Ltd., Ahmedabad, India
Mo: 9409648767
Email Address: [email protected]
Received 25 April 2013; accepted 07 May 2013
Abstract
The objective of the present study was to formulate, optimize and evaluate the bilayer tablet of telmisartan and amlodipine
besilate both as immediate release layers for the effective management of patients with severe hypertention. Telmisartan
layer (220 mg) was prepared by wet granulation using various superdisintegrants. Amlodipine besilate layer (100 mg) was
also prepared by wet granulation method using various superdisintegrants and binders. On the basis of preliminary trials
conducted in cadila pharmaceuticals, crospovidone XL was optimized as superdisintegrant for telmisartan layer and
croscarmellose sodium and starch paste were optimized as superdisintegrant and binder respectively for amlodipine
besylate later. Both telmisartan and amlodipine besilate layers were optimized using 32 factorial design. In case of
telmisartan layer, meglumine and crospovidone XL were selected as independent variable and in case of amlodipine
besilate starch paste and croscarmellose sodium. In both the layers, % friability, disintegration time, t(80) and Q(10) were
selected as dependent variables. All formulations were evaluated for in vitro drug release analyzed according to various
release kinetic models. Results shows that TF6 was optimized in telmisartan layer which contained meglumine 7.5 % (16
mg) and crospovidone 5 % (11 mg) and AF7 was optimized in amlodipine besilate layer which contained starch paste 5 %
(5 mg) and croscarmellose sodium 3% (3 mg). The study indicate that telmisartan and amlodipine besilate can be used in
combination effectively for the treatment of severe hypertention.
© 2013 Universal Research Publications. All rights reserved
Key words: Bilayer tablet, wet granulation, superdisintegrants, binder.
1. Introduction
Hypertension (HTN) or high blood pressure, sometimes
called arterial hypertension, is a chronic medical
condition in which the blood pressure in the arteries is
elevated. This requires the heart to work harder than normal
to circulate blood through the blood vessels[1]. Blood
pressure is summarized by two measurements, systolic and
diastolic, which depend on whether the heart muscle is
contracting (systole) or relaxed between beats (diastole).
Normal blood pressure at rest is within the range of 100-
140mmHg systolic (top reading) and 60-90mmHg diastolic
(bottom reading). High blood pressure is said to be present
if it is persistently at or above 140/90 mmHg. If this disease
is not controlled on time, it may lead to heart attack, brain
stroke or kidney damage. Hence there is a need to develop
a proper medication or combination of two or more
medications that would control hypertension for longer
period of time[2].
Immediate Release Tablets are those tablets which are
designed to disintegrate and release their medication
with no special rate controlling features, such as special
coatings and other techniques[3,4]. Recently immediate
release tablets have started gaining popularity and
acceptance as a drug delivery system, mainly because they
are easy to administer, has quick onset of action is
economical and lead to better patient compliance[5].
Bilayer tablet system contains two layers containing two
incompatible drugs each formulated in single layer[6]. Such
tablets are commonly used to avoid chemical
incompatibilities of formulation components by physical
separation[7]. Bilayer release tablets can have 1) Both
immediate release layers 2) Both sustained release layers.
3) One immediate release and one sustained release layer.
In this system both the layers are of immediate release
pattern[8].
Telmisartan is a potent, long lasting, nonpeptide antagonist
of angiotensin II (AT1) receptor blocker (ARB), which is
indicated for the treatment of hypertension. It blocks the
vasoconstrictor and aldosterone – secreting effects of
angiotensin II. It is practically insoluble in water and
Available online at http://www.urpjournals.com
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Universal Research Publications. All rights reserved
73 International Journal of Pharmacy and Pharmaceutical Science Research 2013; 3(2): 72-78
soluble in strong base. It has the longest half-life of any
ARB (24 hours). It is also used to treat congestive heart
failure and prevent strokes, heart attacks and kidney
damage due to diabetes[9-11].
Amlodipine besylate is a long - acting calcium channel
blocker used in the treatment of chronic stable angina,
vasospastic angina and hypertension. It is a prototype
second generation dihydropyridine calcium channel
blocker. It is sparingly soluble in water and has longer
duration of action. It inhibits calcium ion influx across the
cell membranes selectively with a greater effect on vascular
smooth muscle cells than on cardiac muscle cells. Serum
calcium concentration is not affected by amlodipine
besylate. It has a half-life of 30- 50 hours. It is used in
combination with other antihypertensives or
antianginals[12-14].
On the basis of various preliminary trials conducted in
cadila pharmaceuticals Ltd., crospovidone XL and
meglumine were optimized as superdisintegrant and
alkalinizer respectively for telmisartan part and
croscarmellose sodium and starch paste were optimized as
superdisintegrant and binder respectively. So, here the main
aim of the research work was to measure the effect of
change in concentration of these optimized ingredients
using 32 full factorial design.
2. Materials and Method
Telmisartan, Amlodipin Besylate, sodium hydroxide
pellets, meglumine, microcrystalline cellulose pH102,
crospovidone XL, dibasic calcium phosphate, maize starch,
colour lake of ponceau 4R, croscarmellose sodium,
colloidal silicon dioxide, purified talc and magnesium
stearate were provided by Cadila Pharmaceuticals Ltd.
2.1 Telmisartan Layer:
To the weighed quantity of water dissolve dispensed
quantity of sodium hydroxide pellets followed by
telmisartan and meglumine. Stirr the resultant solution until
yellowish solution is obtained. Granulate the sifted quantity
of microcrystalline in RMG using yellowish solution of
drug with other excipients. Dry these granules at 60º C ±
10ºC. Pass the dried granules through #20 sieve. Finally,
crospovidone XL and magnesium stearate were added and
mixed well for 5 minutes in cage blender and collected for
compression.
2.2 Amlodipine Besylate Layer:
Weighted quantity of amlodipine besylate, dicalcium
phosphate, maize starch and colour Lake Ponceau 4R were
sifted through # 40 sieve and mix well. Binder solution was
prepared by adding weighted quantity of maize starch in
optimum quantity of hot water and stirred continuously till
translucent paste forms. Cool it to below 40ºC. Add
prepared paste into above mixed blend and granules were
prepared. Prepared granules were dried at 60ºC ± 10ºC.
Pass these granules through #20 sieve. Add croscarmellose
sodium, colloidal silicon dioxide, purified talc and maize
starch to the above dried granules and mix for 7 minutes.
Finally add weighted quantity of magnesium stearate to the
above granules and mix for 3 minutes in cage blender.
2.3 Compression of bilayer tablets:
Specific amount of telmisartan granules was compressed
lightly first and then amlodipine besylate granules was
placed on it and again compressed using a double
compression machine with a punch size of 13/32 inch
standard concave circular shape with plain surface.
2.4 Evaluation of Powdered Material[15]
2.4.1 Bulk and Tapped density:
Both bulk and tapped densities were determined and
expressed in gm/cm3. The bulk density and tapped density
were calculated using the following equations.
Bulk density (Bd) = M/Vo
Where, M = mass of powder taken
VO = apparent unstirred volume
Tapped density (Td) = M/Vf
Where, M = weight of sample powder taken
Vf = tapped volume
2.4.2 Compressibility index:
The Compressibility index of the powder blend was
determined by Carr’s Compressibility index. The formula
for Carr’s index is as below.
C.I. = {Td-Bd)/ Td} ×100
Where, Td = tapped density,
Bd = bulk density
2.4.3 Hausner ratio: The Hausner ratio is an index of ease of powder flow. It is
calculated by following equation.
Hausner ratio = Td /Bd
Where, Td = tapped density,
Bd = bulk density
2.4.4 Angle of repose: The angle of repose of powder blend was determined
according to fixed funnel and free standing cone method.
Angle of repose (ϴ) was calculated using the following
equation.
Tan θ = H/R
Therefore, Angle of repose = tan θ-1
(H /R)
Where, H = height of the powder cone,
R = radius of the powder cone
2.5 Evaluation of tablets[16]
2.5.1 Weight variation test
To study weight variation, twenty tablets of each
formulation were weighed using an electronic balance
(Provider: Sartorius engineering Pvt. Ltd, Germany, Model
no.: BSA2202S-CW) and the test was performed according
to the official method. Determinations were made in
triplicate.
Table 1: Weight variation limit (as per IP)
Average weight of tablet (mg) % Difference
80 or less 10
From 80 to 250 7.5
More than 250 5
2.5.2 Thickness Tablet thickness can be measured using a simple procedure.
5 tablets were taken and their thickness was measured
using Vanier calipers (Provider: Mitutoyo engineering Pvt.
Ltd, Japan, Model no.: CD-8”CSX). The thickness was
measured by placing tablet between two arms of the Vanier
calipers.
2.5.3 Hardness
The hardness of the tablets was determined using Monsanto
hardness tester (Provider: Inweka engineering Pvt. Ltd,
74 International Journal of Pharmacy and Pharmaceutical Science Research 2013; 3(2): 72-78
Model no.: IHT-100). For each batch five tablets were
tested.
2.5.4 Friability
Tablets equivaleny to 6.5 gm were weighed and placed in
the Roche friabilator (Provider: Electrolab engineering Pvt.
Ltd, Model no.: EF-2) and apparatus was rotated at 25 rpm
for 4 minutes. After revolutions, the tablets were dedusted
and weighed again. The percentage friability was measured
using formula,
% F = {1-(Wt/W)} ×100
Where, % F = Friability in percentage
W = Initial weight of tablets
Wt = Weight of tablets after revolution
2.5.5 Tablet disintegration time
The disintegration time (DT) of the tablets was determined
in 0.1 N HCl at 37 ± 0.5oC using disintegration test
apparatus (Provider: Electrolab engineering Pvt. Ltd,
Model no.: ED-2 SAPO and ED-3 PO). One tablet was
placed in each of the 6 tubes of the basket and the time
taken for all the tablets to disintegrate and pass through the
wire mesh was recorded. The disintegration time should not
be more than 15 minutes. Determinations were made in
triplicate.
2.6 Mathematical and statistical analysis:
A 32 factorial design was employed considering amount of
meglumine (X1) and crospovidone XL (X2) for telmisartan
part and croscarmellose sodium (X1) and maize starch
paste (X2) for amlodipine besylate part as two independent
variables. By applying factorial, 9 batches were prepared
for both the parts respectively. Friability (Y1),
Disintegration time (Y2), % drug release in 10 min (Q10)
(Y3) and time required for the 90 % drug release (T90)
(Y4) were selected for both the layers as response to study
the effect of independent variables on their respective layer
formulations. Analysis of variance (ANOVA) was
performed to study the statistical significance of
independent variables and their interaction term.
Polynomial equations were calculated for as responses.
Design expert (Version 8.0.7.1) was used for the statistical
and mathematical analysis.
2.6.1 Factorial design for telmisartan:
The factors were selected based on preliminary study. The
concentration of meglumine (X1) and concentration of
crospovidone XL (X2) were selected as independent
variables. Friability, disintegration time, time required for
90 % drug release (t90) and % drug release in 10 minutes
(Q10) were selected as dependent variables. Coded values -
1, 0 and +1 were 5%, 7.5% and 10% for independent factor
meglumine (X1) and 2%, 3.5% and 5% for independent
factor crospovidone XL (X2).
2.6.1.1 Formulation of telmisartan part (TF1-TF9):
Table 2: Formulation of telmisartan immediate release layer using 32 full factorial design.
Ingredients (mg/tablet) Batches
TF1 TF2 TF3 TF4 TF5 TF6 TF7 TF8 TF9
Telmisartan 40.00 40.00 40.00 40.00 40.00 40.00 40.00 40.00 40.00
Sodium Hydroxide 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00
Meglumine 11.00 11.00 11.00 16.00 16.00 16.00 22.00 22.00 22.00
Purified water Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S.
Crospovidone XL 4.50 7.50 11.00 4.50 7.50 11.00 4.50 7.50 11.00
Microcrystalline Cellulose pH102 159.50 156.50 153.00 154.50 151.50 148.00 148.50 145.50 142.00
Magnesium stearate 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00
Total weight 220
2.6.2 Factorial design for amlodipine besylate:
The concentration of croscarmellose sodium (X1) and
concentration of maize starch paste (X2) were selected as
independent variables. Friability, disintegration time, time
required for 90 % drug release (t90) and % drug release in
10 minutes (Q10) were selected as dependent variables.
Coded values -1, 0 and +1 were 1%, 2% and 3% for
independent factor croscarmellose sodium (X1) and 5%,
7.5% and 10% for independent factor maize starch paste
(X2).
2.6.2.1 Formulation of amlodipine besylate part (AF1-AF9):
Table 3: Formulation of amlodipine besylate immediate release layer using 32 full factorial design.
Ingredients (mg/tablet) Batches
AF1 AF2 AF3 AF4 AF5 AF6 AF7 AF8 AF9
Amlodipine Besylate 6.93 6.93 6.93 6.93 6.93 6.93 6.93 6.93 6.93
Croscarmellose Sodium 1.00 1.00 1.00 2.00 2.00 2.00 3.00 3.00 3.00
Colour Lake of ponceau 0.40 0.40 0.40 0.40 0.40 0.40 0.40 0.40 0.40
Maize Starch (Paste) 5.00 7.50 10.00 5.00 7.50 10.00 5.00 7.50 10.00
Purified water Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S.
Dibasic Calcium Phosphate 72.17 69.67 67.17 71.17 68.67 66.17 70.17 67.67 65.17
Maize Starch 12.00 12.00 12.00 12.00 12.00 12.00 12.00 12.00 12.00
Colloidal Silicon Dioxide 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
Purified talc 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50
Magnesium Stearate 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
Total weight 100
75 International Journal of Pharmacy and Pharmaceutical Science Research 2013; 3(2): 72-78
3. Results and Discussion:
By measuring various parameters of batches (TF1-TF9) and (AF1-AF9), various results were obtained are as below.
3.1 Evaluation results of telmisartan part: Table 4: Evaluation parameters of formulations TF1-TF9
Formulation
Code
Evaluation parameters
Weight
variation
(n=20)
Thickness ±
S.D. (mm)
(n = 5)
Hardness ±
S.D. (kg/cm2)
(n = 5)
Friability
(%)
Disintegration time
(sec)
Drug
content
(%)
TF1 0.221±0.009 2.94 ± 0.028 4.3 ± 0.4 0.412 71 ± 4 98.34
TF2 0.225±0.010 2.91 ± 0.044 4.2 ± 0.7 0.396 67 ± 1 98.78
TF3 0.221±0.012 2.95 ± 0.019 4.4 ± 0.5 0.372 61 ± 5 104.50
TF4 0.220±0.010 2.90 ±0.038 4.2± 0.2 0.258 89 ± 2 98.54
TF5 0.224±0.007 2.92 ± 0.044 4.1± 0.4 0.226 66 ± 1 100.93
TF6 0.221±0.004 2.95 ± 0.016 4.2± 0.3 0.188 54 ± 3 106.65
TF7 0.223±0.007 2.96 ± 0.045 4.5 ± 0.6 0.482 109 ± 3 96.94
TF8 0.224±0.010 2.93 ± 0.056 4.2 ± 0.5 0.465 88 ± 5 105.16
TF9 0.221±0.005 2.94 ± 0.047 4.4 ± 0.3 0.462 69 ± 1 102.10
3.1.1 In vitro drug release profile of batches TF1-TF9:
Figure 1. In vitro drug release profile of batches TF1-TF9
3.1.2 Statistical results of telmisartan part:
Table 5: Results of dependent factors for telmisartan part Batch code Y1 (Friability) (%) Y2 (Disintegration Time) (Seconds) Y3 (Q10) (%) Y4 (T90) (min)
TF1 0.412 71 78.42 41
TF2 0.396 67 80.16 38
TF3 0.372 61 82.57 34
TF4 0.258 89 81.64 37
TF5 0.226 65 83.83 32
TF6 0.188 54 85.22 30
TF7 0.482 109 80.32 43
TF8 0.465 88 81.76 41
TF9 0.462 69 82.79 40
Table 6: Summary of Result of Regression Analysis for Telmisartan layer Friability (%)
Response (Y1) b0 b1 b2 b12 b11 b22
FM 0.225 0.0366 -0.0231 0.0027 0.206 -0.0015
P Value 0.00014 0.0050 0.01817 0.04937 0.000156 0.87159
Polynomial Y = 0.225 + 0.036667X1 - 0.02317X2 + 0.00275X1X2 + 0.206X12 - 0.0015X2
2
Disintegration Time (sec)
Response (Y1) b0 b1 b2 b12 b11 b22
FM 67.88889 11.16667 -14.1667 -7.5 8.166667 2.166667
P Value 0.000218 0.007458 0.003767 0.037986 0.041558 0.52037
Polynomial Y = 67.88889 + 11.16667X1 - 14.1667X2 - 7.5X1X2 + 8.166667X12+2.166667X2
2
Q10 (%)
Response (Y1) b0 b1 b2 b12 b11 b22
FM 83.62333 0.62 1.7 -0.42 -2.56 -0.09
P Value 0.030505 0.011035 0.000588 0.042514 0.0089 0.668757
Polynomial Y = 83.62333 + 0.62X1 + 1.7X2 - 0.42X1X2 - 2.56X12 - 0.09X2
2
T90 (min)
Response (Y1) b0 b1 b2 b12 b11 b22
FM 32.66667 1.833333 -2.83333 1 6.5 0.5
P Value 0.0000219 0.017573 0.005182 0.024027 0.002292 0.507715
Polynomial Y = 32.66667+1.833333X1-2.83333X2+1X1X2+6.5X12+0.5X2
2
76 International Journal of Pharmacy and Pharmaceutical Science Research 2013; 3(2): 72-78
3.1.3 Model for various dependent variables:
Using design expert software, contour plots and response
surface plots were prepared for various dependent variables
like friability, disintegration time, T90 and Q10.
Figure 2. Contour plots and response surface plots showing
effects of meglumine (X1) and crospovidone XL (X2) on
friability and disintegration time.
Here, blue colour indicates least response and red colour
indicates highest response. Various contour plots and
response surface plots shows that batch TF6, having 7.5 %
of meglumine and 5 % of crospovidone XL, gives least
friability as well as disintegration time.
Here also, as stated in friability and disintegration time,
blue colour indicates least response and red colour indicates
highest response. Various contour plots and response
surface plots shows that batch TF6, having 7.5 % of
meglumine and 5 % of crospovidone XL, gives highest Q10
and least T90.
So, from above statistical evaluation, batch TF6 provided
most optimized results.
3.2 Evaluation results of amlodipine besylate part:
Table 7: Evaluation parameters of formulations AF1-AF9
Formulation Code
Evaluation parameters
Weight variation
(n=20)
Thickness ± S.D.
(mm) (n =
5)
Hardness ± S.D.
(kg/cm2) (n = 5)
Friability
(%)
Disintegration time
(sec)
Drug
content
(%)
AF1 0.100±0.010 1.23 ± 0.036 4.8 ± 0.2 0.725 85 ± 2 98.26
AF2 0.102±0.012 1.21 ± 0.028 4.7 ± 0.6 0.796 114 ± 5 99.10
AF3 0.104±0.023 1.24 ± 0.014 4.2 ± 0.1 0.943 135 ± 1 96.35
AF4 0.101±0.020 1.20 ± 0.038 4.9 ± 0.5 0.358 79 ± 3 103.41
AF5 0.103±0.010 1.25 ± 0.044 4.8 ± 0.8 0.596 94 ± 1 100.58
AF6 0.103±0.016 1.24 ± 0.042 4.2 ± 0.8 0.791 101 ± 5 98.48
AF7 0.102±0.021 1.22 ± 0.046 4.8 ± 0.5 0.127 60 ± 3 104.31
AF8 0.104±0.013 1.21 ± 0.023 4.8 ± 0.3 0.387 72 ± 2 99.25
AF9 0.100±0.019 1.20 ± 0.051 4.3 ± 0.5 0.602 79 ± 6 105.89
3.2.1 In vitro drug release profile of batches AF1-AF9:
77 International Journal of Pharmacy and Pharmaceutical Science Research 2013; 3(2): 72-78
3.2.2 Statistical results of telmisartan part:
Table 8: Results of dependent factors for telmisartan part
Batch code Y1 (Friability) (%) Y2 (Disintegration Time) (Seconds) Y3 (Q10) (%) Y4 (T90) (min)
AF1 0.725 85 82.63 33
AF2 0.796 114 80.19 35
AF3 0.943 135 78.38 40
AF4 0.358 79 83.82 30
AF5 0.596 94 81.36 32
AF6 0.791 101 79.61 36
AF7 0.127 60 85.93 28
AF8 0.387 72 83.16 30
AF9 0.602 79 81.28 34
Table 9: Summary of Result of Regression Analysis for Amlodipine Besylate layer Friability (%)
Response (Y1) b0 b1 b2 b12 b11 b22
FM 0.583 -0.22467 0.187667 0.06425 0.015 -0.002
P Value 0.000231 0.000656 0.001119 0.040104 0.606053 0.943193
Polynomial Y = 0.583 - 0.22467X1 + 0.187667X2 + 0.06425X1X2 + 0.015X12 - 0.002X2
2
Disintegration Time (sec)
Response (Y1) b0 b1 b2 b12 b11 b22
FM 93.66667 -20.5 15.16667 -7.75 -0.5 -3.5
P Value 0.00008237 0.0012643 0.00305942 0.0346415 0.05719858 0.3241818
Polynomial Y = 93.66667 - 20.5X1 + 15.16667X2 - 7.75X1X2 - 0.5X12 - 3.5X2
2
Q10 (%)
Response (Y1) b0 b1 b2 b12 b11 b22
FM 81.34889 1.528333 -2.185 -0.1 0.331667 0.371667
P Value 0.0001299 0.00003211 0.000011003 0.016686644 0.01436931 0.0104744
Polynomial Y = 81.34889 + 1.528333X1 - 2.185X2 - 0.1X1X2 + 0.331667X12 + 0.371667X2
2
T90 (min)
Response (Y1) b0 b1 b2 b12 b11 b22
FM 31.88889 -2.66667 3.166667 -0.25 0.666667 1.166667
P Value 0.00046422 0.00012986 0.000077 0.044293612 0.03420018 0.0074571
Polynomial Y = 31.88889 - 2.66667X1 + 3.166667X2 - 0.25X1X2 + 0.666667X12 + 1.166667X2
2
3.2.3 Model for various dependent variables:
Using design expert software, contour plots and response
surface plots were prepared for various dependent variables
like friability, disintegration time, T90 and Q10.
Figure 5. Contour plots and response surface plots showing
effects of corscarmellose sodium (X1) and maize starch
paste (X2) on friability and disintegration time.
Various contour plots and response surface plots shows that
batch AF7, having 3 % of croscarmellose sodium and 5 %
of maize starch paste, gives least friability as well as
disintegration time.
Various contour plots and response surface plots shows that
batch AF7, having 3 % of croscarmellose sodium and 5 %
of maize starch paste, gives highest Q10 and least T90.
So, from above statistical evaluation, batch AF7 provided
most optimized results.
3.3 Stability Study:
Stability study of bi-layer optimized formulation TF6-AF7
was conducted at accelerated stability condition (400C ±
20C/75%RH ± 5%RH) as well as long term stability
condition (250C ± 2
0C/60%RH ± 5%RH) for 1 month. The
Figure 6. Contour plots and response surface plots showing
effects of corscarmellose sodium (X1) and maize starch
paste (X2) on Q10 and T90.
78 International Journal of Pharmacy and Pharmaceutical Science Research 2013; 3(2): 72-78
result reveals that there was no major change in assay, in
vitro dissolution study, hardness, disintegration time and
friability. So, prepared formulation is optimized based on
stability study as well.
4. Conclusion:
From the preliminary trials, crospovidone XL was
optimized as superdisintegrant for telmisartan part and
croscarmellose sodium & starch paste were optimized as
superdisintegrant and binder respectively for amlodipine
besylate part. From the results of 32 factorial design,
formulations TF6 which contained 11 mg of crospovidone
XL and 16 mg of meglumine has been selected as best
formulation in telmisartan layer and AF7 which contain 3
mg of croscarmellose sodium and 5 mg of starch paste has
been selected as best formulation in amlodipine besylate
layer. Stability study of bi-layer tablet shown that there was
no major effect of temperature and relative humidity on
assay, in vitro drug release profile, friability, disintegration
time and hardness. Experience with Bilayer immediate
release tablet reveals that this is a fruitful approach to
prepare Bilayer immediate release tablet for better action of
telmisartan and amlodipine besylate.
5. Acknowledgement:
The authors are grateful to Cadila Pharmaceuticals Ltd
(Gujarat, India) for providing materials and equipment for
the research.
6. References:
1. O. Suzanne, A. Zaman, D.A. Calhoun, Pathogenesis of
Hypertention, Ann. Intern. Med. 139 (2003) 761-776.
2. M. Epstein, J.R. Sowers, Diabetes mellitus and
Hypertention, Hypertention. 19 (1992) 403-418.
3. K. Harbir, Processing Technologies for pharmaceutical
tablet: a review, Int.Res. J. Pharm. 3(7) (2012) 20-23.
4. L.V. Allen, G.P. Nicholas, C.A. Howard, Ansel’s
pharmaceutical dosage forms & drug delivery systems.
(8th
eds.), Lippincott Williams & Wilkins, New Delhi,
2005, pp-246-268.
5. L. Lachman, H.A. Lieberman, J.L. Kanig, The Theory
and Practise of Industrial Pharmacy. (2nd
eds),
Varghese Publishing House, Bombay, 1991, pp-317-
320.
6. P. Mehul, N.S. Ganesh, M. Tamizh, Challenges in the
formulation of Bi-layered tablets: A Review, Int. J.
Pharm. Res. Dev. 2(10) (2010) 30-42.
7. D.D. Rohan, D.V. Gowda, M. Nawaz, N.M. Deepak,
Bilayer Tablets- An Emerging Trend: A Review, Int. J.
Pharm. Sci. Res. 2(10) (2011) 2534-2544.
8. P.A. Hiten, T.K. Ajay, A Novel approach of bilayer
tablet technology: A Review, Int. Res. J. Pharm. 3(5)
(2012) 44-49.
9. http://www.drugs.com/monograph/telmisartan.html
10. http://www.rxlist.com/micardis-drug.htm
11. http://en.wikipedia.org/wiki/Telmisartan
12. http://en.wikipedia.org/wiki/Amlodipine
13. http://www.rxlist.com/norvasc-drug.htm
14. http://www.drugs.com/monograph/amlodipine-
besylate.html
15. J.A.K. Kuzhiyil, A. Senthil, S. Masurkar, J.Karat, B.N.
Vantoor, Formulation and evaluation of immediate
release venlafaxine HCL tablets: comparative study of
superdisintegrants and diluents, Int. Res. J. Pharm. 3(4)
(2012) 324-329.
16. The Indian Pharmacopoeia Commission, Central
Indian Pharmacopoeia Laboratory, Ministry of Health
and Family Welfare, Govt. of India, Sector 23, Raj
Nagar, Ghaziabad 201002, India; 2007;
Pharmaceutical Methods: pp 175-188.
Source of support: Nil; Conflict of interest: None declared
