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RESEARCH ARTICLE
Effect of Different Viscosity Grade of HPMC on Cefixime Trihydrate Sustained Release
Matrix Tablet
Patel BP*1, Patel BK1
1
ABSTRACT
The present work aims to study effect of different viscosity grade of HPMC on cefixime
trihydrate sustained release matrix tablet with a view to prolong drug release in vivo and reduce
frequency of dosing. Cefixime Trihydrate is an orally active third generation cephalosporin. It
has plasma half-life of 3-4 hrs. It is active against Gram+ve as well as Gram-ve bacteria. The
Sustained release matrix tablets were prepared by wet granulation method using various release
retardant polymers like different grade of HPMC, Lactose, MCC, and PVP K-30. The granules
were subjected to pre-compression and post-compression parameters and they were in the
acceptable limits. The in vitro retardation of drug release from HPMC matrices in accordance
with its different proportion and viscosity grade was HPMC K-100M>HPMC K-15M >HPMC
K-4M with ratio of (1, 1.5, 2) individually in formulation F1-F9 and (0.5, 0.75, 1) ratio in F10F12. Among various kinetic models drug release was found to best fit the case II
transport, Zero order release model. A drug-excipient interaction was performed by DSC and
FTIR; results were shown that there was no interaction between drug and excipients used. After
3 months stability study at 400C/75% RH, formulations found to be stable. So as the viscosity
and proportion of HPMC increases release rate from sustained release cefixime trihydrate matrix
tablet decreases.
KEYWORDS
Sustained release matrix tablet, Cefixime Trihydrate, HPMC, Antibiotic
is to achieve better therapeutic activity by
INTRODUCTION
using smallest quantity of drug administered
The oral route is the most acceptable drug
delivery route for patient compliance aspects.
or
twice
daily,
compared
with
115
very
Streptococcus
pyogenes,
Streptococci.4
physico-chemical
drug
matrix
substance.
properties
Hydrophilic
of
polymer
good
in
vitro
activity
against
pneumonia,
Streptococcus
Branhamella
catarrhalis,
concentration
Cefixime
steady-state
HPMC is pH independent. 3
of
uncomplicated
UTI,
otitis
media,
(MEC)
trihydrate
within
inhibit
maintenance
12
hours.
mucopeptide
of
plasma
116
Alembic
Baroda,
K-15M,
Laboratory grade.
pharmaceuticals;
Gujarat.HPMC
Preparation
K-4M,
of
HPMC
Cefixime
Trihydrate
Pre-compression Parameters8, 9
BulkDensity:
by
wet
granulation
technique.
The
Tapped
Density:
Hausners
composed
of
HPMC
K-4M,
whereas
(like-100,150,200).
First
Post-Compression Parameters10-15
117
various
official
and
non
official
specifications.
Hardness10
Hardness indicates the ability of a tablet to
withstand mechanical shocks while handling.
The hardness of the tablets was determined
Monsanto
hardness
tester.
It
is
using
100
Drug content13
Ten
Tablets
were
selected
accurately,
10
was
transferred
to
100
ml
118
Quantity
26.22g
7.78 g
Magnesium Chloride
5 ml
Distilled Water
Up to 1000ml
regression
analysis using
the
following
119
Cefixime
Trihydrate
Stability studies:[2, 6]
provide
desirable drug-release.
Pre-Compression Parameters
Angle of Repose
flow property.
patient
Sustained
convenience.
Release
Therefore,
Japan.[12-15]
Fourier Transforms Infrared Spectroscopy
Post-Compression Parameters
Studies (FTIR)
Fourier
transform
infrared
spectrum of
to be satisfactory.
Hardness
120
Friability
Drug Content
Drug
release
from
HPMC
matrices
polymer
retardation of drug
plays
important
role
release was
in
in
K-4M
0.75
SLOWEST
0.75
0.5
SLOWER
0. 5
0.75
SLOW
121
model).
221.16C,
109.24C,
respectively.
Theses
97.70C,
confirmed
89.66C
drug
DISCUSSION
compliance
increasing
and
containing
HPMCK-100M
122
release
was
decreased.
Formulation
of
Table : 1 Formulation of Cefixime Trihydrate Sustained Release Matrix Tablet (Wt. in mg)
FORMULATION
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
200
200
200
200
200
200
200
200
200
200
200
200
100
150
200
50
75
100
100
150
200
75
100
50
100
150
200
100
50
75
LACTOSE
125
100
75
125
100
75
125
100
75
45
45
45
MCC
90
65
40
90
65
40
90
65
40
45
45
45
PVP K 30
25
25
25
25
25
25
25
25
25
25
25
25
Mg. STEARATE
TALC
CODE
CEFIXIME
TRIHYDRATE
HPMC K 4 M
(4,000 mPa s)
HPMC K 15 M
(15,000 mPa s)
HPMC K 100 M
(100,000 mPa s)
123
Bulk Density
(g/cc)
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
0.405 0.0035
0.417 0.0000
0.426 0.0040
0.438 0.0000
0.459 0.0046
0.478 0.0052
0.503 0.0058
0.521 0.0000
0.536 0.0064
0.610 0.0150
0.590 0.0162
0.564 0.0075
Carrs
Hausner Ratio Compressibility
index (%)
0.454 0.0000 1.121 0.0098
10.79 0.7627
0.459 0.0046 1.102 0.0110
9.21 0.9180
0.475 0.0046 1.113 0.0185
10.17 1.4905
0.487 0.0058 1.111 0.0133
9.99 1.0750
0.517 0.0064 1.126 0.0029
11.21 0.1986
0.536 0.0064 1.121 0.0254
10.75 2.0150
0.564 0.0075 1.120 0.0277
10.68 2.2309
0.590 0.0081 1.133 0.0156
11.73 1.2182
0.604 0.0081 1.128 0.0146
11.36 1.1221
0.707 0.0115 1.160 0.0159
13.81 1.1872
0.676 0.0000 1.146 0.0312
12.67 2.3914
0.652 0.0095 1.158 0.0285
13.57 2.1344
Each value is the mean, n = 3 determinations
Tapped
Density (g/cc)
Angle of
Repose (o)
32.55 0.4792
31.48 0.4503
29.98 0.4215
30.23 0.4215
29.28 0.3984
27.97 0.3637
28.61 0.3811
27.15 0.0000
26.38 0.3291
23.34 0.2540
24.61 0.2887
25.47 0.5300
Thickness
(mm)
Diameter
(mm)
Weight
Variation
(mg)
Hardness
(kg/cm2)
Friability
(%)
Swelling
Index
(%)
% Drug
Content
F1
3.50 0.0000
93.17
0.36
63.81
93.83
F3
3.55 0.0115
0.29
66
94.67
F4
3.57 0.0115
0.30
62.91
95
F5
3.60 0.0000
0.27
65.64
96.17
F6
3.64 0.0000
0.25
66.90
96.5
F7
3.63 0.0115
0.22
66.36
96.83
F8
3.65 0.0115
0.21
68.91
97
F9
3.68 0.0000
0.23
70.18
97.67
F10
3.71 0.0115
0.11
75.45
98.67
F11
3.70 0.0000
0.16
73.27
97.67
F12
3.69 0.0115
8.57
0.0577
8.73
0.0577
8.83
0.0577
8.97
0.0577
9.03
0.0577
9.20
0.0000
9.33
0.0577
9.47
0.0577
9.70
0.1000
10.43
0.0577
10.23
0.0577
9.97
0.0577
61.81
3.53 0.0115
550.67
1.1547
550.00
1.0000
550.67
1.1547
551.33
1.5275
549.33
1.1547
549.33
0.5774
549.33
2.0817
551.67
1.5275
550.33
0.5774
548.67
1.1547
550.67
1.1547
550.00
1.0000
0.41
F2
11.02
0.0000
11.08
0.0058
11.13
0.0173
11.17
0.0058
11.21
0.0115
11.30
0.0000
11.35
0.0058
11.37
0.0115
11.43
0.0306
11.63
0.0115
11.56
0.0153
11.51
0.0058
0.18
72.18
97.17
124
Time
(Hrs.)
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
20.01
17.18
13.06
16.41
12.03
11.26
10.75
9.21
7.92
5.61
8.43
13.83
26.14
26.88
21.95
25.07
22.97
16.79
17.30
17.54
12.89
13.64
15.73
19.39
30.84
33.16
27.71
33.91
30.29
25.08
26.11
23.54
21.69
20.16
21.47
26.39
37.32
39.14
34.97
38.89
36.54
35.97
32.89
30.29
28.99
27.69
30.01
31.87
44.59
45.12
40.96
46.15
43.81
40.20
42.48
38.85
34.98
33.68
36.28
40.41
56.24
53.93
50.29
54.97
52.37
48.73
49.79
46.92
46.11
41.21
42.52
46.94
62.54
60.20
53.99
59.18
58.13
54.49
57.33
53.44
51.11
44.63
49.79
48.81
74.95
69.01
59.94
62.06
66.16
59.95
65.12
60.71
58.63
52.90
56.30
51.66
83.32
72.71
67.21
77.00
74.48
67.98
71.64
67.22
64.62
58.90
61.77
63.52
10
90.09
80.72
73.97
79.23
80.48
70.90
77.37
73.97
73.17
64.63
68.26
67.25
11
96.08
87.49
80.99
88.51
84.92
78.13
83.34
78.93
79.70
70.35
75.27
76.29
12
99.23
91.94
86.73
95.55
90.63
84.64
92.67
86.19
81.83
74.78
79.21
82.05
Zero order
0.9903
0.9974
0.9981
0.9932
0.9956
0.9934
0.9976
0.9981
0.9952
0.9968
0.9982
0.9916
Model (R2)
First order
Higuchi
0.7973
0.9581
0.9248
0.9811
0.9404
0.9807
0.8472
0.9721
0.9455
0.9871
0.9625
0.9877
0.9035
0.9829
0.9532
0.9825
0.9659
0.9797
0.9812
0.9869
0.9717
0.9836
0.9341
0.9664
Korsemeyer-peppas
0.9609
0.9926
0.9967
0.9918
0.9980
0.9939
0.9972
0.9987
0.9952
0.9949
0.9992
0.9869
125
2.500
F1
F2
F3
F4
F5
10
11
12
F1
2.000
Log % CD Remaining
100
90
80
70
60
50
40
30
20
10
0
F2
1.500
F3
1.000
F4
0.500
F5
F6
0.000
F7
-0.500
F6
10 11 12
F7
Time (Hrs.)
Time (Hrs.)
100
90
80
70
60
50
40
30
20
10
0
KORSEMEYER-PEPPAS MODEL
F1
F2
F3
F4
F5
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
F6
Log % CDR
HIGUCHI MODEL
2.000
1.750
1.500
1.250
1.000
0.750
0.500
0.250
0.000
F1
F2
F3
F4
F5
0.000
0.500
1.000
F6
1.500
Fig : 1 In vitro drug release and Kinetic analysis parameters for Cefixime Trihydrate
Sustained Release Matrix Tablet
126
Cefixime Trihydrate
Table : 6 Stability Study Data of Cefixime Trihydrate Sustained Release Matrix Tablet
STABILITY STUDY DATA (mean S.D , n = 3)
Hardness (kg/cm2)
code
Drug Content
After 3 months
Initial
(400C
After 3 months
Initial
75%RH)
F3
F6
F9
F10
F11
F12
8.83
0.0577
9.20
0.0000
9.70
0.1000
10.43
0.0577
10.23
0.0577
9.97
0.0577
(400C
After 3 months
Initial
75%RH)
(400C
75%RH)
8.78 0.0153
94.67
92.02
86.73
85.22
9.14 0.0000
96.5
95.75
84.64
83.20
9.64 0.0153
97.67
95.00
81.86
79.82
10.36 0.0577
98.67
97.14
74.78
74.00
10.19 0.0000
97.67
96.45
79.21
78.14
9.91 0.0577
97.17
95.68
82.05
81.11
127
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G.,
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matrix
tablet
of
8.
(2004).
Cefixime
5.
6.
7.
and
(Eds.).p.108-145.
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Vallabh
prakashan;
293- 345.
4.
9.
3.
Biopharmaceutics
Pharmacokinetics, 397-510
11.
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12.
matrix.
Drugs.38:524-50.
(19):1201-1210.
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129