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Original Article
ISSN
Print
Online
International Journal of
Pharmacy and Industrial
Research
2231 3648
2231 3656
*,1
J.K.K.M.M.R.F College of Pharmacy, Komarapalayam, Namakkal (dt), TN, India - 638 183.
2
C.L.Baid Metha College of Pharmacy, Thorapakkam, Chennai, TN, India - 600 097.
______________________________________________________________
Abstract
The present study was to establish Bi-layer tablets containing Metformin hydrochloride as extended release
layer and Glibenclamide as immediate release layer for the treatment of type II diabetes mellitus. Extended
release layer was prepared by wet granulation method using HPMC 100 and ethyl cellulose as polymers.
Immediate release layer were prepared by using super disintegrants such as sodium starch glycolate and
cross carmellose sodium. The granules were evaluated for bulk density,tapped density, compressibility
index,and hausners ratio. The granules showed satisfactory flow properties. The tablets were subjected to
weight variation test, hardness test, friability test, drug content test ,wetting time and water absorption test.
All the tablets were passed the tests. The in-vitro release studies were carried out in phosphate buffer of PH
6.8 for 12 hours using USP-type II paddle apparatus. The in-vitro release profiles of drug from sustained
release layer could be best expressed by Higuchis equation as plots showed high linearity (R2> 0.988). The
formulations (F12, F27) having immediate release layer produces effect within 30 minutes followed by
sustained release (98.90%) at 12 hours.
Keywords: Bi-layer tablet, Glibenclamide,Metformin hydrochloride,Higuchis equation.
_______________________________________________________________________________________
most prominent being the high dose2 (1.5-2.0
Introduction
Metformin hydrochloride is a highly water-
activator
in
noninsulin
(PAI)
hypertriglyceridemia
levels
and
in
both
during
the
treatment.4
Gastrointestinal
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
165
Glibenclamide
is
second
generation
Materials
Metformin
Remedies
Hydrochloride,
ltd.
Chennai.
Glibenclamide
Sodium
starch
100
increases
by
5mg
of
of
the
patient
glibenclamide
compliance
and
500mg
purchased
from
Rolex
Laboratory
Methods
respective
drug,
polymer
and
sustained
more
concentration.
release
preparation
Thus,
with
potentially
avoiding
operational conditions.
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166
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
Thermal
analysis
for
characterizing
aerosil
previously
passes
through
60#.
per tablet.
Analysis of excipients compatibility by
stability studies
The
active
ingredients
Hcl,
Metformin
hydrochloride,
microcrystalline
through
compressed
60#.
Prepared
with
round
granules
shaped
were
concave
Ingredients
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
Glibenclamide
10
12
Crospovidone
10
12
Croscarmellose sodium
10
12
Povidone K 30
10
10
10
10
10
10
10
10
10
10
10
10
Microcrystalline cellulose
73
73
73
71
71
71
69
69
69
67
67
67
Mannitol
50
50
50
50
50
50
50
50
50
50
50
50
Lactose
50
50
50
50
50
50
50
50
50
50
50
50
Aerosil
02
02
02
02
02
02
02
02
02
02
02
02
10
Magnesium stearate
Total
04
04
04
04
04
04
04
04
04
04
04
04
200
200
200
200
200
200
200
200
200
200
200
200
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Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
167
Ingredients
F13
F14
F15
F16
F17
F18
F19
F20
F21
F22
F23
F24
F25
F26
F27
Metformin
hydrochloride
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
HPMC 100
100
125
150
175
200
100
50
100
100
100
Ethyl cellulose
100
125
150
175
200
50
100
100
100
100
Microcrystalline
cellulose
160
135
110
85
60
160
135
110
85
60
110
110
60
55
50
PVP K 30
20
20
20
20
20
20
20
20
20
20
20
20
20
25
30
Talc
08
08
08
08
08
08
08
08
08
08
08
08
08
08
08
Aerosil
04
04
04
04
04
04
04
04
04
04
04
04
04
04
04
Magnesium stearate
08
08
08
08
08
08
08
08
08
08
08
08
08
08
08
Isopropyl alcohol
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
q.s
800
800
800
800
800
800
800
800
800
800
800
800
800
800
800
Total
Where,
V0 = initial volume;
Vf = final volume
Angle of repose
Hausners ratio
Hausners was calculated with the following
Where,
formula
density
and
tapped
density
were
Weight
variation
friability
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hardness
and
168
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
Where,
seconds.
repose,
bulk
density,
tapped
density,
friability,
release tablet.
hardness
and
thickness
were
Drug content13
at 300nm.
absorbance at 232nm.
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Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
169
Where,
is the zero order rate constant expressed in
units of concentration/time and t is the time in
hours.
Where,
Where,
DSC
profiles
for
ethyl
cellulose,
and
excipients.
studies
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170
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
bulk
and
tapped
density
of
the
1.12,
and
1.13
respectively.
And
the
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
0.323
0.325
0.334
0.333
0.308
0.312
0.314
0.324
0.310
0.314
0.327
0.329
0.362
0.367
0.373
0.372
0.349
0.350
0.355
0.356
0.341
0.345
0.349
0.351
10.77
11.44
10.45
10.48
11.74
10.85
11.54
8.98
9.09
8.98
6.30
6.26
1.12
1.13
1.11
1.11
1.13
1.12
1.13
1.09
1.10
1.09
1.06
1.06
30.52
28.30
29.42
29.29
28.21
28.70
27.12
27.14
26.56
27.64
27.69
26.00
F2,
of
immediate
release
formulations
were
F5,
F8,
and
prepared
with
sodium.
From
with
croscarmellose
F11
this
croscarmellose sodium.
F12
and
produced
necessary
hardness.
The
was
compared
that
indicates
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the
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
percentage
release
of
171
cumulative
their
layer glibenclamide
layer
the drug.
formulation
F1F12
revealed
the
variation
(mg) s.d
Friability
Hardness
Thickness
(%)
(kg/cm2)
(mm)
Wetting
Water
time
absorption
(sec)
ratio
Disintegration
time (sec)
F1
201.60.57
0.26
4.230.15
4.940.12
121
71.42
3481.00
F2
201.30.57
0.43
4.130.20
5.000.07
53
61.90
92.32.51
F3
202.01.00
0.75
4.000.20
5.010.24
49
52.38
47.61.53
F4
201.31.52
0.86
4.160.21
5.190.06
91
70.00
191.31.53
F5
201.31.52
0.31
4.000.20
5.170.05
49
60.00
80.30.58
F6
201.01.73
0.54
4.100.17
5.080.19
47
52.38
46.31.53
F7
199.33.51
0.81
4.160.06
5.170.06
59
68.42
1801.00
F8
197.63.21
0.94
4.200.17
5.170.05
48
57.14
79.34.50
F9
199.61.52
0.33
4.200.10
5.010.10
45
45.00
29.30.58
F10
201.31.15
0.45
3.960.21
4.930.03
57
65.00
101.61.53
F11
199.32.51
0.63
4.060.15
5.120.09
46
55.00
76.31.53
F12
200.03.00
0.87
4.100.10
5.210.08
36
35.00
261.00
Graph 1
Graph 2
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172
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
Graph 3
F13
F14
F15
F16
F17
F18
F19
F20
F21
F22
F23
F24
0.160
0.159
0.158
0.144
0.143
0.159
0.153
0.159
0.154
0.155
0.152
0.154
0.164
0.169
0.174
0.181
0.190
0.160
0.163
0.179
0.185
0.196
0.154
0.159
2.43
5.91
9.19
20.44
24.73
0.62
6.13
11.17
16.75
20.91
1.29
3.14
1.02
1.06
1.10
1.25
1.32
1.00
1.06
1.12
1.20
1.26
1.01
1.03
25.94
26.56
28.81
32.57
34.43
25.46
27.75
29.89
30.52
33.69
25.34
25.40
combination
metformin
metformin
respectively.
polymer
increases,
release
of
the
drug
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of
both
hydrochloride
hydrochloride
hydrophilic
for
at
12
12th
and
hours.
hour
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
173
and
concentration
graphs.
ethyl
cellulose
for
was
the
retarding
Weight variation
(mg) S.D
Friability (%)
Hardness (Kg/cm2)
Thickness (mm)
F13
800.30.59
1.10
3.530.06
6.230.03
F14
800.61.53
1.07
3.700.10
6.040.02
F15
799.60.58
0.96
3.960.15
6.010.01
F16
799.30.58
0.91
4.100.10
6.100.01
F17
801.62.31
0.75
4.330.17
5.990.01
F18
801.30.58
1.03
4.000.00
6.210.01
F19
799.61.15
1.00
3.930.15
6.070.02
F20
802.01.73
0.87
4.100.10
6.020.02
F21
799.32.08
0.64
4.530.05
6.100.01
F22
799.62.51
0.37
5.100.10
6.020.02
F23
800.31.53
0.87
4.230.15
6.070.02
F24
800.60.58
0.71
4.800.10
5.980.12
F25
803.32.51
0.63
5.030.05
6.190.01
F26
803.03.46
0.66
5.300.10
6.020.02
F27
799.30.58
0.59
5.430.06
6.080.01
Graph 4
Graph 5
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optimum
metformin
174
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
Graph 6
0.782,
and
0.998
respectively.
equation,
which
was
0.510
indicated
release
optimized
of
was
tablet.
Immediate
release
layer
www.ijpir.com
by
comparing
their
hardness,
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
175
release
tablet.
and
99.28%
of
metformin
matrix
for
glibenclamide
and
References
1.
2.
matrix
4.
3.
5.
metformin
Hcl,
6.
International
(2009), p. 49-53.
7.
Thams,
with
J.
3026.
triacetyl--cyclodextrin,
Eur.
8.
and
R.
Keith
Campbell,
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176
Aishwarya R et al., Int. Journal of Pharmacy & Industrial Research Vol 02 Issue 02 Apr Jun 2012
9.
2, (2007), p. 664.
1, (2007), p.182.
11. Friability,
Indian
1,
(2007), p.182.
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