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: Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers 1111
International Journal of Pharmaceutical Sciences and Nanotechnology
Volume 3 Issue 3 October - December 2010
Research Paper
Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some
Hydrophilic Polymers on the Release Rate and In Vitro Evaluation
S.K. Singh.1*, S.B. Bothara2, S. Singh3, R. Patel4 and R. Dodia5
1
ABSTRACT: Extending the residence time of a dosage form at a particular site and controlling the release of drug from
the dosage form are useful especially for achieving controlled plasma level of the drug as well as improving bioavailability.
The objective of this study was to extend the GI residence time of the dosage form and control the release of Tramadol HCl
using mucoadhesive tablet to achieve controlled plasma level of the drug which is especially useful for 12 hrs. Matrix tablets
of Tramadol HCl were formulated using different mucoadhesive polymers namely guar gum, xanthan gum and Methocel
(HPMC K15M and HPMC K100M). Formulations were evaluated for preformulation parameters, in vitro drug release profile
and release kinetics. The formulations were found to have good preformulation characteristics. FTIR spectroscopy indicated
the absence of any significant chemical interaction within dug and excipients. The release mechanism of Tramadol HCl from
matrix tablets indicated anomalous (non-Fickian) transport mechanism and followed zero order kinetics. The retention time
of the mucoadhesive tablet on the mucous membrane were investigated to develop a bioadhesive polymer-based controlled
release delivery system and to evaluate the performance of such a delivery devices. The combination of HPMC K15: HPMC
K100: Xanthan gum (1:2:1) and HPMC K 100: Xanthan gum (2:2) showed a greater bioadhesive strength as compared to
single gum and other hydrophilic polymer combination tablet. The stability studies were performed on optimized formulation
as per ICH guideline, result showed that there was no significant change in physical characteristic, adhesive strength and In
vitro release.
1111
Experimental Methods
Materials
Tramadol Hydrochloride were procured from Intas
Pharmaceutical Ltd., Ahmedabad, Hydroxy Propyl Methyl
cellulose K100M, Hydroxy Propyl Methyl cellulose K15M
were procured from Colorcon Asia Pvt. Ltd., Lactose,
Microcrystalline cellulose (Avicel pH 102) and Guar gum
were procured from Signet Chemical Corp, PVP K 30
were procured from Nice Chemicals Laboratory,
Magnesium Stearate and Talc from Loba Chemical. All the
chemicals and other reagents used in the study were of AR
grade.
Formulation and Optimization of Excipient
Sustained release mucoadhesive oral matrix tablets
containing Tramadol HCl were prepared by wet
granulation technique using variable concentrations of
HPMC K15M, HPMC K100M, Xanthan gum, Guar gum.
In all case, the amount of the active ingredient is 100mg.
All the ingredients except Avicel pH 102, magnesium
stearate and talc were blended in blender uniformly.
Granulation was done with sufficient binding solution of
PVP K30 and isopropyl alcohol. The lubricated granules
were compressed into tablet using 9 mm standard concave
punch with 10 station single rotary Clit (Jemkay) machine
and keeping average weight 240 mg. All Tramadol HCl
loaded matrix tablet were stored in airtight container at
room temperature for further study. Tablet of batch F1F3,
F4F6, F7F9 and F10F12 contain only single
1113
3
3
Talc
Mg. stearate
240
60
Avicel PH 102
Total Weight in mg
24
--
Xanthan gum
q.s
--
HPMC K100M
IPA
--
HPMC K15M
PVP K-30
50
Guar gum
F1
100
Ingredient*
Tramadol HCl
240
45
q.s
24
--
--
--
75
100
F2
240
10
q.s
24
--
--
--
100
100
F3
240
60
q.s
24
--
--
50
--
100
F4
240
45
q.s
24
--
--
75
--
100
F5
F7
240
60
q.s
24
--
50
--
--
100
F8
240
45
q.s
24
--
75
--
--
100
240
10
q.s
24
--
--
100
--
100
F6
240
10
q.s
24
--
100
--
--
100
F9
240
60
q.s
24
50
--
--
--
100
F10
240
45
q.s
24
75
--
--
--
100
F11
240
10
q.s
24
100
--
--
--
100
F12
S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers 1113
240
10
q.s
24
--
50
50
--
100
F13
240
10
q.s
24
50
--
50
--
100
F14
240
10
q.s
24
50
50
--
--
100
F15
240
10
q.s
24
25
50
25
--
100
F16
Weight
Variation (mg)
Hardness
2
(kg/cm )
Thickness
(mm)
Friability
(%)
Drug content
uniformity (mg)
F1
240.75.02
6.70.252
3.030.11
0.55
98.94
F2
240.54.00
6.60.289
2.800.05
0.58
99.10
F3
239.63.99
6.40.462
2.760.05
0.53
98.92
F4
239.43.77
7.10.361
2.700.15
0.39
98.72
F5
240.33.01
6.60.173
2.660.05
0.41
98.19
F6
240.32.72
7.40.551
2.930.15
0.48
98.92
F7
240.12.17
6.40.436
2.550.08
0.61
97.10
F8
240.22.29
6.90.306
2.620.05
0.72
99.28
F9
239.82.05
7.10.458
2.530.052
0.67
98.30
F10
240.12.47
6.60.173
2.810.076
0.48
97.46
F11
240.02.11
6.60.208
2.760.115
0.39
98.19
F12
241.02.55
6.70.208
2.830..064
0.47
98.82
F13
240.12.13
6.70.666
2.530.052
0.54
97.30
F14
241.12.57
6.40.603
2.810.076
0.56
97.46
F15
240.52.23
7.10.208
2.760.115
0.44
99.19
F16
240.32.25
7.00.200
2.830..064
0.38
99.82
Batch
no.
F1
0.624
0.852
1.041
1.166
1.248
1.250
--
--
F2
0.558
0.862
1.045
1.186
1.065
1.024
--
--
F3
0.672
0.918
1.122
1.245
1.327
1.347
1.306
--
F4
0.616
0.950
1.116
1.241
1.324
1.344
1.386
--
F5
0.120
0.399
0.605
0.852
0.934
1.140
1.181
1.201
F6
0.126
0.224
0.477
0.646
0.857
0.983
1.025
1.152
F7
0.204
0.532
0.660
0.830
0.915
1.000
1.043
1.085
F8
0.259
0.570
0.674
0.736
0.860
0.901
0.942
0.983
F9
0.561
0.880
1.160
1.380
1.460
1.480
1.520
1.540
F10
0.688
0.934
1.016
1.119
1.140
1.222
1.305
1.322
F11
0.599
0.803
0.926
1.008
1.131
1.172
1.254
1.295
F12
0.674
0.922
1.150
1.138
1.145
1.276
1.321
1.333
F13
0.526
0.822
1.045
1.142
1.198
1.224
1.236
1.242
F14
0.656
0.942
1.124
1.145
1.185
1.215
1.266
1.275
F15
0.554
0.852
0.999
1.256
1.456
1.654
1.789
1.952
F16
0.599
0.769
0.921
1.164
1.289
1.546
1.654
1.899
S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers 1115
ADHESIVE STRENGTH
Adhesive strength
35
30
25
20
15
10
5
0
F1
F2
F3
F4
F5
F6
F7
F8
Batch No.
Swelling Index
Swelling Index
2
1.9
1.8
1.7
1.6
1.5
1.4
1.3
1.2
1.1
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
F1
F2
F3
F4
F5
F6
F7
F8
F9
F10
F11
F12
F13
F14
F15
F16
0
4
5
Tim e (hrs)
G
E
A
I
F
Bioadhesive strength
9.81
100
0
0
0
0
0
0
0
0
0
1
0.624
0.558
0.672
0.616
0.120
0.126
0.204
0.259
2
0.852
0.862
0.918
0.950
0.399
0.224
0.532
0.570
3
1.041
1.045
1.122
1.116
0.605
0.477
0.660
0.674
Time (hrs)
4
5
1.166 1.248
1.186 1.065
1.245 1.327
1.241 1.324
0.852 0.934
0.646 0.857
0.830 0.915
0.736 0.860
6
1.250
1.024
1.347
1.344
1.140
0.983
1.000
0.901
7
--1.306
1.386
1.181
1.025
1.043
0.942
8
----1.201
1.152
1.085
0.983
Table 3 Contd
S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers 1117
Batch no.
0
0
0
0
0
0
0
0
F10
F11
F12
F13
F14
F15
F16
1
0.688
0.599
0.674
0.526
0.656
0.554
0.599
2
0.934
0.803
0.922
0.822
0.942
0.852
0.769
3
1.016
0.926
1.150
1.045
1.124
0.999
0.921
Time (hrs)
4
5
1.119 1.140
1.008 1.131
1.138 1.145
1.142 1.198
1.145 1.185
1.256 1.456
1.164 1.289
6
1.222
1.172
1.276
1.224
1.215
1.654
1.546
7
1.305
1.254
1.321
1.236
1.266
1.789
1.654
8
1.322
1.295
1.333
1.242
1.275
1.952
1.899
F1
F2
F3
F4
F5
F6
F7
F8
c u m . % d ru g re le a s e
100
90
80
70
60
50
40
30
20
10
0
0
6
7
Time (hrs)
10
11
12
F9
F10
F11
F12
F13
F14
F15
F16
Correlation
Higuch
coefficient
Peppas Model
Model
Hixsoncrowell
Correlation
Correlation
Slope
Correlation
Correlation
coefficient
coefficient
(n)
coefficient
coefficient
F1
-13.600
0.9820
0.6911
0.8608
0.9928
0.5377
0.9934
0.9434
F2
-11.413
0.9784
0.5142
0.9415
0.9980
0.5178
0.9986
0.9881
F3
-9.6875
0.9621
0.4396
0.9547
0.9260
0.4958
0.9949
0.9062
F4
-10.800
0.9735
0.3661
0.9268
0.9540
0.7006
0.9438
0.9631
F5
-9.5172
0.9891
0.1805
0.5091
0.9912
0.7111
0.9954
0.9780
F6
-8.3734
0.9903
0.3228
0.8009
0.9906
0.6830
0.9946
0.9290
F7
-9.6523
0.9906
0.3447
0.9118
0.9879
0.7200
0.9931
0.9733
F8
-8.8515
0.9931
0.3120
0.8947
0.9821
0.7325
0.9924
0.9609
F9
-8.5790
0.9895
0.3244
0.8802
0.9767
0.7994
0.9939
0.9540
F10
-10.443
0.9855
0.1356
0.1968
0.9961
0.5778
0.9982
0.9879
F11
-8.7675
0.9611
0.2897
0.9888
0.9939
0.5626
0.9938
0.9979
F12
-8.3800
0.9819
0.3111
0.9489
0.9849
0.5526
0.9913
0.9879
F13
-6.8411
0.9821
0.1842
0.9575
0.9972
0.7815
0.9942
0.9884
F14
-6.8554
0.9413
0.2565
0.9154
0.9841
0.6266
0.9670
0.9699
F15
-7.1766
0.9989
0.1084
0.5241
0.9702
0.7836
0.9891
0.9460
F16
-7.3398
0.9966
0.2385
0.7941
0.9641
0.7639
0.9885
0.9040
F16
Mucoadhesion
force (N)
Mucoadhesive
strength (g)
Mucoadhesion
force (N)
29.580.042
0.29010.0004
31.690.071
0.31080.0006
0.28920.0004
31.4650.035
0.30870.0003
0.28770.0001
31.540.035
0.30950.0003
S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers 1119
Conclusion
The cram was undertaken with an endeavor to formulate
and evaluate effect of hydrophilic polymer on release rate
of mucoadhesive tablet. mucoadhesive tablet were
formulated using, various hydrophilic polymers and their
combinations in varying concentrations. Tablet were
subjected to various evaluation parameters such as
hardness, friability, drug content, mucoadhesive strength
study and In vitro drug release study. It was revealed that
all batches had acceptable physical parameters. The
optimized formulation (F15 and F16) have good
mucoadhesion along with in vitro drug release. It was
observed that all batches followed the equation of zero
order, higuchi matrix and peppas drug release profiles.
Stability studies revealed that there was no significant
change in the hardness, friability, drug content and in vitro
dissolution profile of formulation F15 and F16. Thus these
formulations were stable at different condition of
temperature. The present study shows that there is
influence of polymer on release profile of oral
mucoadhesive tablet. The combination of hydrophilic
synthetic (HPMC) and natural gum (Xanthan gum) can be
used for designing oral mucoadhesive drug delivery
system.
Acknowledgement
The authors are grateful to the Principal and Management
of Shree H.N. Shukla Institute of Pharmaceutical
S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers 1121
References