Result and Discussion 6

Results
RESULT AND DISCUSSION

3.3
EVALUATION
AND
OPTIMIZATION
OF
FLOATING
TABLETS
3.3.1. Physical parameters
3.3.1.A Size and Shape: - The shape tablets were evaluated visually and the
size particularly thickness was measured with the help of screw gauge.
3.3.1.B Weight Variation: - The individual of 20 tabletss from each batch
were weighed accurately to determine the weight variations. As per the USP all the
tablets must within the the range of 5. The sample mean and standard deviation of
each batch of tablets were determined (table).
3.3.1.C Hardness: - The hardness individual 10 tablets from each batch were
determined with the help of Pfizer hardness tester and the sample mean and standard
deviation were calculated for each batch (table).
3.3.1.D Friability: - It
was determined with Roche friabilator apparatus
(Hicon, India). Following formula was used to determination of friability:

Friability =
(Initial wt - Final wt / Initial wt ) 100
Table 3.2: Average hardness and friability

S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Formulation code
DP1
DP2
DP3
DP4
DP5
DP6
DP7
DPH
H
P1
P2
P3
P4
P5
P6
P7
PH
DPC1
DPC2
PC1
PC2
Average hardness (kg/cm 2)

2.50.52
2.470.21
1.960.23
3.010.45
3.30.17
3.170.25
2.830.32
3.90.26
4.20.4
2.130.36
2.260.11
1.80.2
2.730.4
3.010.11
3.230.15
2.730.42
4.160.15
2.870.31
2.830.33
3.230.25
2.90.92
Average friability (%)

0.89 0.015
0.870.002
0.890.019
0.800.023
0.800.023
0.750.011
0.810.049
0.630.079
0.510.087
0.910.016
0.890.067
0.890.043
0.820.017
0.820.019
0.780.075
0.830.051
0.650.064
0.780.053
0.710.089
0.830.031
0.750.091
Dept. of Pharmaceutical Sciences S.S.I.T.M.

63
Results
Mean SD, n = 3
Table 3.3: Average weight and thickness
Average thickness (mm)
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
Formulation Code
DP1
DP2
DP3
DP4
DP5
DP6
DP7
DPH
Average Weight (mg)

492.331.53
610.331.53
7322.65
731.932.32
782.461.32
703.771.1
764.772.35
5.54 0.73
5.670.19
6.620.11
6.540.19
6.50.1
6.430.26
6.590.13
6.480.37
733.432.46
6.410.47
9.
731.871.38
5.560.73
10.
P1
4941.73
11.
P2
6111.3
12.
P3
732.63.13
0.5.720.31
6.630.15
6.570.13
13.
P4
729.172.41
6.510.17
14.
P5
781.871.35
15.
P6
703.11.37
16.
P7
763.32.05
17.
PH
733.131.59
6.640.34
6.610.21
6.50.18
6.790.73
18.
DPC1
762.82.46
6.910.64
19.
DPC2
792.111.44
20.
PC1
763.031.53
21.
PC2
792.11.15
6.840.49
6.970.14
Mean SD, n = 3
3.3.1.D Floating lag Time and duration of floating: - The buoyancy lag time and
Duration of floating were determined in the USP Dissolution apparatus II in an acidic
environment (0.1N HCL, 900 ml, 50 RPM). The time interval between introduction of
the tablets in to the dissolution medium and its buoyancy to the top of the dissolution
medium was taken as buoyancy lag time and duration of buoyancy was observed

64
Results
visually. The sample mean and standard deviation of each batch of tablets were
determined (n = 3).
3.3.1.E Density: - The apparent densities of the tablets were calculated from their
volumes and masses in triplicate. Both parameters were determined in 0.1 N HCL
after floating the tablets. The volumes V of the spherical tablets were calculated from
their radii (determine with a micrometer gauge i.e. screw gauge) using the
mathematical equation for a circle (4 /3 r3). The sample mean and standard deviation
of each batch of tablets were determined (n = 3).
3.3.1.F Dimensional Stability: - The dimensional stability of formulation was studied
using USP Dissolution Apparatus II. The dissolution medium was 0.1N HCL and the
volume being 900 ml. The temperature was maintained at 37 5 0C. The rotation
speed was 50 rpm. The dimensional stability of the theophylline floating tablets was
observed visually. The sample mean and standard deviation of each batch of tablets
were determined (Table 3.3).
3.3.2 Content Uniformity: - The drug content of at least 6 tablets from each batch
was determined. The tablets were weighed collectively, pulverized. The weight equal
to single tablet was weighted and dissolved in 100 ml of 0.1N HCL solutions. The
drug solution was filtered. Aliquots of filtrate was diluted suitably and analyzed
spectrophotometrically (Shimadzu 1700, Japan)at 270 nm. The sample mean and
standard deviation of each batch of tablets were determined. (Table 3.4).
Table 3.4: Floating capabilities of different batches of theophylline floating
matrix tablets
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
Formulation
code
Density
(mg/cm3)
DP1
DP2
DP3
DP4
DP5
DP6
DP7
DPH
0.97.023
1.04 0.027
1.047 0.024
0.978 0.085
1.020.011
1.0230.069
0.960.021
0.7920.085
Floating
lag (sec)
347 8.69
2897.51
1022.56
781.93
713
982.51
60.72.52
47.32.08
Floating capabilities
Floating
Dimensional
duration(hours)
stability
11.3 0.25
Note retain
17.90.38
Note Retain
> 24
Retain
> 24
Retain well
> 24
Retain well
22 0.61
Retain
> 24
Retain well
> 24
Retain well

65
Results
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
H
P1
P2
P3
P4
P5
P6
P7
PH
DPC1
DPC2
PC1
PC2
0.955.024
0.9380.015
0.95.059
1.006.075
0.9750.018
0.9480.083
1.0220.026
1.003.027
0.9440.044
0.960.011
0.950.023
0.9670.36
0.950.23
10.31.53
3554.58
2944.58
1202.52
85.75.03
79.31.53
1055.29
69.72.08
551
55.11.53
452
61.51.32
501.63
> 24
12.6 0.56
19.86
> 24
> 24
> 24
20.2 0.85
> 24
> 24
> 24
> 24
> 24
> 24
Retain well
Note retain
Note Retain,
Retain
Retain well
Retain well
Retain
Retain well
Retain well
Retain well
Retain well
Retain well
Retain well
Mean SD, n = 3
Table 3.5: Drug content uniformity of different batches of theophylline floating
matrix tablets
S.No.
Formulation
code
Labeled
amount of
drug (mg) (X)
Actual amount
of drug(mg) (Y)
Percentage of
drug content
(Y/X 100)
1.
DP1
200
1980.36
99.0
2.
DP2
200
1991.57
99.5
3.
DP3
200
198.30.98
99.12
4.
DP4
200
199.51.57
99.75
5.
DP5
200
198.31.42
99.15
6.
DP6
200
198.22.37
99.1
7.
DP7
200
196.21.05
98.1
8.
DPH
200
197.42.57
98.7
9.
200
197.31.55
98.65
10.
P1
200
198.60.75
99.3
11.
P2
200
197.30.45
98.65
12.
P3
200
197.52.63
98.75
13.
P4
200
196.22.07
98.1

66
Results
14.
P5
200
197.41.71
98.7
15.
P6
200
197.170.85
98.58
16.
P7
200
196.672.15
98.33
17.
PH
200
199.330.77
99.66
18.
DPC1
200
199.271.57
99.63
19.
DPC2
200
199.021.35
99.51
20.
PC1
200
199.481.18
99.74
21.
PC2
200
198.351.21
99.17
Mean SD, n = 3
3.3.3 In-Vitro Release Study: -The release of theophylline from the tablets was
studied using the USP dissolution apparatus I. The dissolution medium was 0.1N HCL
and the volume being 900 ml. The temperature was maintained at 37 0. 5 0C. The
rotation speed 100 rpm. Five ml of aliquot was withdrawn at a predetermine intervals
of .1,2,3,4,5,6,7,8,10,12,hours. The medium was replenished with five ml of fresh
0.1N HCL at each time. The drug solution was filtered. Aliquots of filtrate was diluted
suitably and analyzed spectrophotometrically (Shimadzu 1700, Japan) at 270 nm. %
of drug released was calculated for each interval.

67
Results
3.3.3: B In -Vitro Release data of Theophylline from Different Formulations
Prepared with Dehusk Psyllium Husk in 0.1N HCL
Table 3.6: In-Vitro release data of theophylline from batch DP1 in 0.1N HCL
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Time
(hrs)
Absorb.
0.5
1
2
3
4
5
6
7
8
10
12
0.150
0.304
0.426
0.512
0.592
0.642
0.694
0.741
0.788
0.874
0.962
Concentration in (mg)
ml
0.0276
0.0559
0.0785
0.0943
01090
0.1880
0.1278
0.1365
0.1451
0.1610
0.1772
5 ml
0.138
0.280
0.392
0.471
0.545
0.591
0.639
0.683
0.756
0.805
0.886
900 ml
24.86
50.39
70.61
84.86
98.12
106.4
115.03
122.85
130.59
144.86
159.45
Cum. drug
release
% Cum.
drug release
24.86
50.53
71.03
85.67
99.40
108.23
117.44
125.96
134.33
149.33
164.44
Total amount of drug = 200 mg, dilution factor = 10 slope = 0.0543
Fig 3.1: In-Vitro release of theophylline from batch DP1 in 0.1N HCL

68
12.43
25.26
35.51
42.84
49.70
54.12
58.72
62.98
67.16
74.66
82.22
Results
S.No.
Time
(hrs)
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
0.5
1
2
3
4
5
6
7
8
10
12
Absorb.
0.144
0.224
0.296
0.384
0.442
0.482
0.513
0.521
0.546
0.662
0.776
ml
0.2099
0.0413
0.0534
0.0707
0.0814
0.0887
0.0921
0.0969
0.0994
0.1220
0.1420
5 ml
0.105
0.206
0.267
0.354
0.410
0.438
0.460
0.484
0.497
0.620
0.715
900 ml
18.9
37.13
48.07
63.65
73.26
79.89
82.87
87.18
89.50
109.72
128.62
Cum. drug
release
% Cum.
drug release
18.90
37.23
48.38
64.22
74.19
80.86
84.29
89.43
92.23
112.95
132.47
9.45
18.62
24.19
32.11
37.09
40.43
42.14
44.72
46.12
56.48
66.23
70
% Cum. drug release
60
50
40
30
20
10
0
0
10
12
14
Time (hrs)

69
Results
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Time
(hrs)
0.5
1
2
3
4
5
6
7
8
10
12
Absorb.
0.102
0.176
0.228
0.364
0.382
0.412
0.434
0.469
0.488
0.511
0.558
ml
0.0188
0.0324
0.0457
0.0670
0.0703
0.0758
0.0799
0.0863
0.0899
0.0941
0.1028
5 ml
0.094
0.162
0.228
0.335
0.352
0.379
0.399
0.432
0.449
0.471
0.514
Cum. Drug
release
900 ml
16.90
29.17
41.10
60.33
63.31
68.29
71.93
77.73
80.88
84.10
92.49
16.90
29.27
41.59
60.82
64.36
69.46
73.48
79.68
83.26
87.51
95.79
% Cum.
drug release
8.42
14.63
20.79
30.41
32.18
34.72
36.74
39.84
41.69
43.78
47.89
60
% Cum. drug re le ase
50
40
30
20
10
0
0
10
15
Time (hrs)

70
Results
S.No.
Time
(hrs)
Absorb Concentration in (mg)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.087
0.160
0.080
14.42
14.42
2.
1
0.174
0.032
0.160
28.83
28.92
3.
2
0.242
0.045
0.223
40.11
40.29
4.
3
0.286
0.526
0.263
47.41
47.57
5.
4
0.342
0.063
0.315
50.69
57.41
6.
5
0.378
0.696
0.384
62.65
63.69
7.
6
0.428
0.078
0.394
70.94
72.33
8.
7
0.461
0.085
0.424
76.41
78.19
9.
8
0.494
0.091
0.455
81.88
84.09
10.
10
0.531
0.098
0.489
88.01
90.67
11.
12
0.578
0.116
0.532
95.80
98.95
% Cum.
drug
release
7.21
14.46
20.14
23.93
28.71
31.85
36.16
39.1
42.04
45.34
49.47
% Cum . drug release
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)

71
Results
S.No.
Time
(hrs)
Absorb Concentration (mg)

Cum. Drug
.
release
ml
5 ml
900 ml
1.
0.5
0.078
0.014
0.072
12.93
12.93
2.
1
0.166
0.031
0.153
27.51
27.58
3.
2
0.224
0.041
0.210
37.13
37.42
4.
3
0.234
0.043
0.215
38.79
39.22
5.
4
0.271
0.050
0.250
44.92
45.57
6.
5
0.324
0.059
0.298
53.7
54.60
7.
6
0.386
0.071
0.355
63.98
64.96
8.
7
0.422
0.077
0.389
69.94
71.49
9.
8
0.476
0.087
0.438
78.89
80.84
10.
10
0.538
0.099
0.495
89.17
91..55
11.
12
0.588
0.108
0.541
97.46
100.33
% Cum.
Drug
release
6.46
13.79
18.71
19.61
22.78
27.30
32.48
35.75
40.42
45.78
50.17
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)

72
Results
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.097
0.018
0.089
19.08
16.08
2.
1
0.184
0.034
0.169
30.5
30.59
3.
2
0.256
0.047
0.236
42.43
42.68
4.
3
0.304
0.056
0.279
50.39
50.88
5.
4
0.357
0.067
0.328
59.17
59.95
6.
5
0.376
0.069
0.348
62.67
63.77
7.
6
0.422
0.078
0.389
69.94
71.39
8.
7
0.474
0.087
0.437
78.56
80.40
9.
8
0.498
0.092
0.459
82.54
84.22
10.
10
0.537
0.099
0.494
89.01
91.45
11.
12
0.603
0.111
0.555
99.99
102.83
% Cum.
drug
release
8.04
15.29
21.34
25.44
29.97
31.88
35.69
40.2
42.11
45.73
51.42
60
50
40
30
20
10
0
0
0.2
0.4
0.6
0.8
Tim e(hrs)

73
Results
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.086
0.017
0.083
14.85
14.85
2.
1
0.149
0.027
0.137
24.66
24.74
3.
2
0.216
0.039
0.199
35.80
36.02
4.
3
0.266
0.048
0.245
44.08
44.51
5.
4
0.306
0.057
0.285
51.22
51.88
6.
5
0.337
0.621
0.310
55.85
56.81
7.
6
0.398
0.073
0.366
65.97
67.23
8.
7
0.416
0.077
0.383
68.95
70.51
9.
8
0.469
0.086
0.432
77.73
79.73
10.
10
0.502
0.092
0.462
89.70
85.64
11.
12
0.559
0.103
0.515
92.65
95.54
% Cum.
drug
release
7.42
12.37
18.01
22.25
25.94
28.41
33.62
35.25
39.87
42.82
47.77
60
% Cum . drug relase
50
40
30
20
10
0
0
0.2
0.4
0.6
Tim e(hrs)

74
Results
3.3.3.B In-Vitro Release Data of Theophylline from Different Formulations
Prepared with Husk Psyllium in 0.1N HCL
Table 3.13: In-Vitro release data of theophylline from batch P1 in 0.1N HCL
Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.173
0.032
0.159
28.79
28.79
2.
1
0.331
0.061
0.305
54.86
55.02
3.
2
0.454
0.084
0.420
75.37
75.83
4.
3
0.519
0.096
0.478
86.04
86.92
5.
4
0.599
0.110
0.552
99.35
100.71
6.
5
0.648
0.119
0.597 107.40
109.32
7.
6
0.683
0.126
0.630
113.27
115.77
8.
7
0.741
0.136
0.682 122.73
125.77
9.
8
0.772
0.142
0.711 127.95
131.64
10.
10
0.859
0.158
0.791 142.38
146.91
11.
12
0.942
0.174
0.867 156.13
161.45
% cum . drug release
S.No.
Time
(hrs)
% Cum.
drug
release
14.39
27.51
37.92
43.46
50.35
54.65
57.88
62.88
65.82
73.45
80.72
90
80
70
60
50
40
30
20
10
0
0
Time(hrs)
10
15
Fig 3.8: In-Vitro release of theophylline from batch P1 in 0.1N HCL

75
Results
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0140
0.026
0.13
23.25
23.25
2.
1
0.251
0.046
0.23
41.76
41.89
3.
2
0.352
0.069
0.33
58.42
58.78
4.
3
0.409
0.075
0.38
67.79
68.48
5.
4
0.466
0.086
0.43
77.3
78.37
6.
5
0.488
0.089
0.54
80.82
82.32
7.
6
0.502
0.092
0.46
83.20
85.15
8.
7
0.519
0.96
0.48
86.02
88.44
9.
8
0.525
0.097
0.49
87.02
89.91
10.
10
0.579
0.107
0.53
95.97
99.34
11.
12
0.671
0.124
0.62
111.22
115.11
% Cum.
drug
release
11.63
20.95
29.39
34.24
39.19
41.16
42.57
44.23
44.96
48.67
57.56

76
Results
S.No.
Time
(hrs)
Absorb
.
Concentration (mg)
ml
5 ml
1.
0.5
0.115
0.0212 0.106
2.
1
0.198
0.0360 0.180
3.
2
0.305
0.0562 0.280
4.
3
0.341
0.0628 0.314
5.
4
0.387
0.0713 0.356
6.
5
0.408
0.075
0.376
7.
6
0.430
0.079
0.396
8.
7
0.455
0.084
0.419
9.
8
0.468
0.086
0.430
10.
10
0.499
0.092
0.460
11.
12
0.530
0.098
488
Total amount of drug = 200 mg, dilution factor = 10
900 ml
Cum. drug
release
19.06
19.06
32.82
32.92
50.55
50.84
56.52
56.82
64.14
65.03
67.62
68.86
71.27
72.89
75.41
77.43
77.57
79.65
82.11
85.40
87.85
91.17
slope = 0.0543
% Cum.
drug
release
9.53
16.46
25.42
28.41
32.51
34.43
36.44
38.71
39.82
42.69
45.58
%Cum . drug release
50
40
30
20
10
0
0
10
15
Tim e(hrs)

77
Results
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.093
0.0171 0.086
15.41
14.41
2.
1
0.183
0.0337 0.169
30.33
30.42
3.
2
0.273
0.0503 0.251
45.27
45.52
4.
3
0.291
0.0540 0.268
48.23
48.74
5.
4
0.349
0.0640 0.321
57.85
58.62
6.
5
0.371
0.0683 0.340
61.49
62.59
7.
6
0.422
0.0777 0.389
69.94
71.38
8.
7
0.43
0.0792 0.396
71.27
73.09
9.
8
0.45
0.0828 0.414
74.59
76.79
10.
10
0.481
0.0890 0.443
79.72
82.74
11.
12
0.551
0.1010 0.505
91.33
93.79
% Cum.
drug
release
7.71
15.21
22.76
24.37
29.31
31.29
35.69
36.55
38.39
41.37
46.89
%Cum. drug release
50
40
30
20
10
0
0
Time(hrs)
10
15

78
Results
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.079
0.0156 0.073
13.09
13.09
2.
1
0.173
0.0319 0.159
28.67
28.75
3.
2
0.232
0.0427 0.214
38.45
38.68
4.
3
0.262
0.0483 0.240
43.20
43.65
5.
4
0.304
0.0559 0.280
50.40
51.07
6.
5
0.387
0.0713 0.356
64.14
65.11
7.
6
0.394
0.0726 0.360
65.30
66.63
8.
7
0.418
0.0768 0.385
69.28
70.96
9.
8
0.454
0.0846 0.418
75.25
77.32
10.
10
0.504
0.0932 0.470
83.47
86.35
11.
12
0.578
0.1065 0.532
95.80
98.52
% Cum.
drug
release
6.55
14.37
19.34
21.82
25.54
32.55
33.31
35.48
38.66
43.18
49.26
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)
Fig3.12: In-Vitro release of theophylline from batch P5 in 0.1N HCL

79
Results
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.119
0.0219
0.11
19.72
19.72
2.
1
0189
0.0348
0.17
31.33
31.44
3.
2
0.286
0.0526
0.20
47.4
44.68
4.
3
0.316
0.0582
0.29
52.38
52.92
5.
4
0.340
0.0626
0.31
56.35
57.18
6.
5
0.378
0.0696
035
62.64
63.78
7.
6
0.391
0.0720
0.36
64.81
66.29
8.
7
0.435
0.0801
04
72.1
73.95
9.
8
0.462
0.0851
0.43
76.57
78.82
10.
10
0.495
0.0912
0.46
82.04
84.72
11.
12
0.565
0.1041
0.52
93.65
96.79
% Cum.
drug
release
9.86
15.72
23.84
26.46
28.59
31.89
33.15
36.97
39.41
42.36
48.39
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)

80
Results
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.089
0.016
0.08
14.75
14.75
2.
1
0.151
0.028
0.14
25.03
25.11
3.
2
0247
0.046
0.23
40.94
41.16
4.
3
0.276
0.051
025
45.75
46.19
5.
4
0.302
0.056
0.28
50.06
50.76
6.
5
0.338
0.062
0.31
56.02
57.00
7.
6
0.369
0.068
034
61.2
62.45
8.
7
0.415
0.76
038
68.78
70.41
9.
8
0.437
0.080
040
72.43
74.43
10.
10
0.484
0.89
0.45
80.22
82.63
11.
12
0.534
0.098
0.49
88.51
91.09
% Cum.
drug
release
7.37
12.55
20.58
23.10
25.38
28.50
31.22
35.21
37.22
41.31
45.55
50
% Cum. drug release
40
30
20
10
0
0
10
15
Time(hrs)

3.3.3.C. In-Vitro Release Data of Theophylline from Different Formulations Prepared
with HPMC K 100 M alone and in combination with Dehusk, Husk Psyllium in 0.1N
HCL

81
Results
Table 3.20: In-Vitro release data of theophylline from batch H in 0.1N HCL
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.098
0.18
0.09
16.24
16.24
2.
1
0.176
0.32
016
29.17
29.26
3.
2
0.234
0.043
0.27
38.79
39.04
4.
3
0.301
0.054
0.28
50.4
50.87
5.
4
0.358
0.66
0.33
59.34
60.10
6.
5
0.421
0.78
0.388
69.78
70.86
7.
6
0.461
0.085
0.424
76.41
77.88
8.
7
0.498
0.92
0.46
82.54
84.44
9.
8
0.599
0.11
0.55
99.00
101.35
10.
10
0.678
0.125
0.63
112.37
115.28
11.
12
0.698
0.129
0.64
115.69
118.94
% Cum.
drug
release
8.12
14.69
19.52
25.44
30.05
35.43
38.94
42.22
50.68
57.63
59.47
70
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)
Fig 3.15: In-Vitro release of theophylline from batch H in 0.1N HCL

82
Results
Table 3.21: In-Vitro release data of theophylline from batch DPH in 0.1N HCL
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.120
0.0184
0.09
16.6
16.6
2.
1
0.201
0.0370
0.19
33.31
33.41
3.
2
0.251
0.0461
0.23
41.6
41.88
4.
3
0.311
0.0573
0.29
51.55
52.05
5.
4
0.369
0.068
0.34
61.16
61.95
6.
5
0.433
0.079
0.39
71.73
72.87
7.
6
0471
0.087
0.43
78.07
79.6
8.
7
0.537
0.098
0.49
89.01
90.94
9.
8
0.565
0.104
0.52
93.65
96.11
10.
10
0.587
0.108
0.54
97.29
100.28
11.
12
0.672
0.134
0.62
111.38
114.91
% Cum.
drug
release
8.3
16.7
20.93
26.03
30.98
36.43
39.80
45.47
48.05
50.14
57.45
70
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)
Fig 3.16: In-Vitro release of theophylline from batch DP H in 0.1N

HCL

83
Results
Table 3.22: In-Vitro release Data of theophylline from batch PH in 0.1N HCL
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.107
0.0197 0.099
17.73
17.73
2.
1
0.213
0.039
0.196
35.3
35.4
3.
2
0.282
0.052
0.26
46.74
47.04
4.
3
0.311
0.057
0.29
51.55
52.1
5.
4
0.367
0.068
0.34
60.83
61.67
6.
5
0.428
0.079
0.39
70.94
72.03
7.
6
0449
0883
0.41
74.43
75.99
8.
7
0.525
0.0967
0.48
87.02
88.89
9.
8
0.543
0.100
0.50
90.0
92.36
10.
10
0.567
0.104
0.52
93.98
96.84
11.
12
0.618
0114
0.57
102.43
105.81
% Cum.
drug
release
8.86
17.7
23.51
26.05
30.83
36.02
38.99
44.45
46.18
48.42
52.91
60
50
40
30
20
10
0
0
10
15
Tm e(hrs)
Fig 3.17: In-Vitro release of theophylline from batch P H in 0.1N HCL

3.3.3.D In-Vitro Release Data of Theophylline from Different Formulations Prepared
with Ac-Di-Sol in combination with Dehusk, and Husk Psyllium in 0.1N HCL

84
Results
Table 3.23: In-vitro release data of theophylline from batch DPC1 in 0.1N HCL
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.96
0.0177 0.088
15.91
15.91
2.
1
0.184
0.0339
0.17
30.50
30.59
3.
2
0.255
0.4710 0.235
42.27
42.52
4.
3
0.317
0.0584 0.292
52.54
53.03
5.
4
0.348
0.064
0.32
57.68
58.46
6.
5
0.394
0.073
0.363
65.68
66.41
7.
6
0.429
0.079
0.395
71.10
72.57
8.
7
0.452
0.083
0.416
74.94
76.61
9.
8
0.526
0.0969 0.480
87.18
89.23
10.
10
0.579
0.1066 0.533
95.97
98.73
11.
12
0.647
0.119
0.596 107.24
110.53
% Cum.
drug
release
7.95
15.29
21.26
26.52
29.23
33.21
36.29
38.31
44.61
49.36
55.27
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)
Fig 3.18: In-vitro release of theophylline from batch DPC1 in 0.1N HCL

85
Results
Table 3.24: In-vitro release data of theophylline from batch DPC2 in 0.1N HCL
Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.101
0.0186
0.93
16.74
16.74
2.
1
0.188
0.35
0.173
31.16
31.25
3.
2
0.275
0.051
0.253
45.58
45.85
4.
3
0.326
0.06
0.3
54.03
54.55
5.
4
0.366
0.067
0.34
60.66
61.48
6.
5
0.412
0.076
0.379
68.29
69.45
7.
6
0.464
0.085
0.427
76.91
78.44
8.
7
0.512
0.094
0.47
84.86
86.83
9.
8
0.552
0.102
0.508
91.49
93.93
10.
10
0.648
0.119
0.597
107.4
110.35
11.
12
0.711
0.131
0.66
117.85
120.02
% Cum. drug release
S.No.
Time
(hrs)
% Cum.
drug
release
8.37
15.63
22.92
27.28
30.74
34.72
39.22
43.41
46.96
55.17
60.01
70
60
50
40
30
20
10
0
0
10
15
Time(hrs)
Fig3.19: In-vitro release of theophylline from batch DPC2 in 0.1N HCL

86
Results
Table 2.25: In-vitro release data of theophylline from batch PC1 in 0.1N HCL
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.091
0.017
0.08
15.08
15.08
2.
1
0.186
0.034
0.17
30.87
30.95
3.
2
0.279
0.051
0.26
46.24
46.49
4.
3
0.325
0.060
0.30
52.87
54.38
5.
4
0.364
0.067
034
60.31
61.12
6.
5
0.405
0.075
0.37
67.13
68.29
7.
6
0.427
0.079
0.39
70.77
72.29
8.
7
0.451
0.083
0.42
74.75
76.66
9.
8
0.512
0.094
0.47
84.86
87.18
10.
10
0.552
0.102
0.52
91.82
94.62
11.
12
0.608
0112
0.56
100.77 104.08
% Cum.
drug
release
7.54
15.48
23.25
27.19
30.56
34.14
36.14
38.33
43.59
47.31
52.04
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)
Fig 3.20: In-vitro release of theophylline from batch PC1 in 0.1N HCL

87
Results
Table 3.26: In-vitro release data of theophylline from batch PC2 in 0.1N HCL
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.112
0.021
0.13
18.56
18.56
2.
1
0.194
0.026
0.18
32.16
31.26
3.
2
0.282
0.520
0.27
46.74
47.02
4.
3
0.332
0.610
0.31
55.03
55.58
5.
4
0.362
0.067
0.33
60.00
60.86
6.
5
0.424
0.078
0.0.39
70.28
71.47
7.
6
00.37
0.081
0.4
72.43
74.04
8.
7
0.479
0.880
044
79.39
81.36
9.
8
0533
0.098
0.49
88.34
90.76
10.
10
0.610
0.112
056
101.11
103.75
11.
12
0.686
0.126
0.63
113.40
116.3
% Cum.
drug
release
9.28
16.13
23.51
27.79
30.43
35.73
37.01
40.69
45.38
51.87
58.15
% Cum.drug release
70
60
50
40
30
20
10
0
0
10
15
Time(hrs)
Fig 3.21: In-vitro release of theophylline from batch PC2in 0.1N HCL
3.3.4: Determination of Swelling Index: - The swelling index of the tablets was
studied using the USP dissolution apparatus I. The dissolution medium was 0.1N HCL
and the volume being 900 ml. The temperature was maintained at 37 0. 5 0C. The

88
Results
rotation speed 100 rpm. The tablets were withdrawn at predetermine intervals of 1, 2,
3, 4, 5, 6 .12 hrs. The tablets were blotted with tissue paper to remove the excess
0.1N HCL and reweighed. The swelling index was calculated by the following
equation: 103,104,105
Swelling index = ( Wt - Wo / Wo ) 100
Where:
Wt is the weight of swelling matrix tablet after t times
Wo is the initial weight of matrix tablet
Table 3.27: Swelling index of theophylline floating matrix tablets from different
formulations in 0.1N HCL
Formulatio
S.No n code
Initial
weigh
t
(mg)
Percentage of swelling index

Time (hrs)
12
1
8
374.17
1.
DP3
732
57.1
131.55 211.4
270.49 306.92 334.9
2.
DP4
732
70.9
139.21 224.0
269.48 289.48 324.8
3.
P3
732
46.03 117.74 182.24 255.5
308.1
317.23
318.16 348.15
306.12
4.
P4
732
58.49 126.66 198.48 248.98 297.8
339.39
215.13
5.
732
85.92 136.66 170.47 225.78 228.83 227.97

312.59
6.
DPC2
792
78.14 145.11 225.0
271.11 308.0
349.11
317.18
7.
PC2
792
65.12 130.61 210.0
259.1
319.8
n=1

89
355.19
Results
Fig 3.22:
Swelling index of theophylline floating matrix tablets from

different formulations in 0.1N HCL
3.3.5. Erosion Studies: - Erosion studies of floating matrix tablets were performed as
reported by Paradkar et al. The preweighed tablets were placed in USP dissolution
Type I dissolution test apparatus and were subjected to dissolution in 900 ml of 0.1N
HCL maintained at 37-C 0.5-C, the speed of basket rotation was 100 rpm. The
matrix system were removed after 12 hrs from the dissolution vessels and dried to
constant weight in hot air oven (Hicon, India) at 50 0C - 60 0C. The percentage matrix
erosion at time 12 hrs was calculated by using following Equation: 103,104,105
Percentage Matrix Eroded = (wt of polymers eroded / wt of initial matrix) 100

Weight of polymers eroded = total weight loss amount of drug released

90
Results
Table 3.28: Percentage matrix eroded after 12 hrs from different formulation in
0.1N HCL
S.No.
Formu Tablet weight (mg)

lation initial remaining
code
drying weight
1.
2.
3.
4.
5.
6.
7.
n=1
DP3
DP4
H
P3
P4
DPC2
PC2
735
731
733
736
732
790
794
586
591
585
578
588
637
616
Total
weight
loss
(mg)
149
140
148
158
144
157
174
Drug
Matrix
released eroded
(mg)
(mg)
93.92
96.98
131.26
89.88
92.92
121.3
134.4
55.08
43.02
16.74
68.12
51.06
35.7
39.6
Percentage
of matrix
eroded
7.49
5.87
2.28
9.25
6.97
4.49
5.01
Fig 3.23: Percentage matrix eroded after 12 hrs from different formulations
in 0.1 N HCL

91
Results
Table 3.29: Characterization of different batches
S.No
Formulation
code
Floatation behavior
1.
DP1
Tablets floated with significant floating lag time good swelling but
not intact, not release the drug up to 24 hrs.
2.
DP2
Tablets floated with significant floating lag time, good swelling but
3.
DP3
Tablets floated with significant floating lag time, good swelling,

remained intact throughout the study, higher erosion, release the drug
up to 24 hrs.
4.
DP4
Tablets showed good buoyancy with good swelling, remained intact

throughout the study, reduced erosion, floating lag time
comparatively reduced, release the drug up to 24 hrs.
5.
DP5

6.
DP6
Tablets floated with good swelling, not remained intact throughout

the study and significant floating lag time.
7.
DP7

throughout the study, floating lag time reduced.
8.
DPH

throughout the study, floating lag time comparatively reduced.
9.

throughout the study, floating lag time was lowest, lowest erosion,
release the drug up to 24 hrs.
10.
P1
11.
P2
12.
P3
Tablets floated with significant floating lag time, good swelling

remained intact, highest erosion; release the drug up to 24 hrs.
13.
P4

14.
P5

92
Results
throughout the study reduced erosion, floating lag time comparatively

reduced, release the drug up to 24 hrs.
15.
P6
Tablets floated with good swelling, not remained intact through the
study and and significant floating lag time.
16.
P7

throughout the study, floating lag time reduced, release the drug up to
24 hrs.
17.
PH

throughout the study, reduced erosion, floating lag time reduced,
release the drug up to 24 hrs.
18.
DPC1

24 hrs.
19.
DPC2

through the study, floating lag time reduced, showed the release up to
the 24 hrs.
20.
PC1

24 hrs.
21.
PC2

throughout the study, floating lag time reduced, showed the release up
to the required period of time.
3.3.4. STUDY ON OPTIMIZED FORMULATIONS

3.3.4.A Effect of Hardness on Buoyancy
Table3.30: Effect of hardness on buoyancy from different formulations
Floating capabilities
S.No.
Batch code
1.
DPC2
Hardness
(kg/cm2)
Floating
lag floating
Time (sec.)
duration(hrs)
452
24
1905
24
NF
50 1.63
24
PC2
2.

93
Results
3.
2008
24
NF
24
10.31.53
24
90.75
24
NF = note float, Mean SD, n = 3

3.3.4 B Effect of RPM on In-vitro Drug Release
Table 3.31: In-vitro release data of drug release from batch DPC2 at 50 RPM
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Time
(hrs)
0.5
1
2
3
4
5
6
7
8
10
12
Absorb.
0.08
0.166
0.234
0.327
0.333
0.411
0.441
0.468
0.510
0.603
0.671
Concentration (mg)
ml
0.0147
0.0305
0.0431
0.0602
0.0613
0.0757
0.0812
0.0862
0.0939
0.1111
0.1234
5 ml
0.0737
0.1529
0.2155
0.3010
0.3067
0.3780
0.4061
0.4310
0.4696
0.5555
03679
Cum. drug
release
900 ml
13.26
27.51
38.78
54.2
55.17
68.12
73.09
77.58
84.53
99.9
111.23
13.26
27.58
38.95
54.64
55.669
68.75
74.25
79.14
86.52
102.12
114.52

94
% Cum.
drug release
6.63
13.79
19.48
27.32
28.58
34.37
37.13
39.57
43.26
51.06
57.26
Results
Fig 3.4: In-vitro release of theophylline from batch DPC2 at 50 RPM
Table 3.32: In-vitro release data of drug release from batch PC2 at 50 RPM
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml
900 ml
1.
0.5
0.09
0.0166 0.829
14.92
14.92
2.
1
0.183
0.0344 0.172
30.96
31.04
3.
2
0.251
0.462
0.231
41.6
41.86
4.
3
0.280
0.0516 0.258
46.41
46.89
5.
4
0.343
0.0632 0.3158 56.85
57.59
6.
5
0.403
0.0742 0.3711 66.79
67.86
7.
6
0.412
0.0759 0.3794 68.28
69.72
8.
7
0.472
0.0869 0.435
78.21
80.02
9.
8
0.510
0.0939 0.4696 84.53
86.78
10.
10
0.601
0.111 0.5555 99.61
101.89
11.
12
0.68.
0.1226 0.6133 110.41
113.47
Fig3.25: In-vitro release of theophylline from batch PC2 at 50 RPM

95
% Cum.
drug
release
7.46
15.52
20.93
23.45
28.79
33.93
34.86
40.01
43.39
50.95
56.71
Results
Table 3.33: In-vitro release data of drug release from batch H at 50 RPM
S.No.
Time
(hrs)

Cum. drug
.
release
ml
5 ml 900 ml
1.
0.5
0.09
0.0166 0.083
14.92
14.92
2.
1
0.185 0.0341 0.170
30.66
30.74
3.
2
0.241 0.0444 0.222
39.94
40.19
4.
3
0.296 0.0545 0.273
49.06
49.54
5.
4
0.362 0.6667 0.333
60.0
60.75
6.
5
0.419 0.7720 0.385
69.45
70.53
7.
6
0.443 0.0820 0.408
73.43
74.89
8.
7
0.482 0.8880 0.444
79.92
81.79
9.
8
0.541 0.0996 0.498
89.67
92.37
10.
10
0.614 0.1131 0.565 101.79
104.6
11.
12
0.682 0.1256 0.628 113.04
116.42
% Cum.
drug
release
7.46
15.39
20.1
24.77
30.37
35.26
37.45
40.89
48.18
52.3
58.21
Fig3.26: In-vitro release of theophylline from batch H at 50 RPM

3.3.4.C. Interaction Study
3.3.4.C.I Thin layer Chromatography: - It was concluded that there was no
significant changed in Rf value of theophylline alone and with polymer. The R f was
found to be 0.665,0.67 and 0.685 for H, DPC2 and PC2 respectively.

96
Results
3.3.4.C.II
Fourier Transform Infrared Spectroscopy: - IR Spectroscopy is of
immense value in establishing drug polymer interaction in solid state. The origin of
any new sharp IR peak or disappearance of any peak associated with a functional
group of the pure drug indicates the drug and polymer in solid state (Techibana and
Neekamura. 1965).
IR spectra of the pure drug and optimized formulations exhibit the following
absorption band.
Table3.34: Wavelength values of drug in the IR spectra
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
Reference
range
3300-3500
1650-1750
1650-1675
1550-1575
1400-1500
1250-1300
1200-1250
700-900
Wavelength (cm-1)
Observed valve
Pure drug
Formulation
3423
3450
1712
1712
1666
1667
1563
1564
1443
1443
1282
1286
1240
1241
843
841
Assignment
N-H(stretch)
C=O(stretch)
C=C(stretch)
C=N(stretch)
C-H(bending)
C-N(vibration)
C-O(vibration
= C-H out plan bending
(A)

97
Results
(B)
Fig 3.27: I.R. Spectra of (A) Psyllium husk (B) Optimized formulation

98
Results
3.3.4. D Release Kinetics
Table 3.35: Release kinetics for formulation DPC2
S.
No.
Time
(hrs)
Square
root
time
(hrs)
Log
time
(hrs )
Cumulativ
e
% drug
release
Log
cumulativ
e % drug
release
Log
cumulative
% drug
remaining
Cube root
cumulative
% drug
remaining
1
2
3
4
5
6
7
8
9
10
11
0.5
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
10
12
0.71
1
1.41
1.73
2
2.24
2.45
2.65
2.83
3.16
3.46
-0.301
0
0.301
0.477
0.60
0.7
0.78
0.85
0.9
1
1.1
8.37
15.63
22.92
27.28
30.74
34.72
39.22
43.41
46.96
55.17
60.01
0.92
1.19
1.36
1.44
1.49
1.54
1.59
1.64
1.67
1.74
1.78
1.96
1.93
1.89
1.86
1.84
1.82
1.78
1.75
1.72
1.65
1.6
4.51
4.39
4.26
4.17
4.11
4.03
3.93
3.84
3.76
3.55
3.41
Table 3.36: Release parameters of optimized formulation DPC2

Zero order
First order
r2
r2
K0
K1
Higuchi
r2
KH
KorsmeyerPeppas
2
r
n
HixsonCrowell
r2
KHC
(h-1)
(h-1)
(h-1/2)
value
(h-1/3)
0.9945 4.2751 0.9954 0.0702 0.997 18.293 0.9921 0.5422 0.9919 0.092

99
Results
(A) Zero order model
(B)First order model
(C) Higuchi model

100
Results
(D) Hixson Crowell model
(E) Korsmeyer-Peppas model

Fig3.28: Release kinetics for formulation DPC2
Table3.37: Release kinetics of formulation PC2
S.
No.
Time
(hrs)
Square
root
time
(hrs)
Log
time
(hrs )
Cumulativ
e
% drug
release
Log
cumulativ
e % drug
release
Log
cumulative
% drug
remaining
Cube root
cumulative
% drug
remaining
1
2
3
4
5
6
7
8
9
10
11
0.5
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
10
12
0.71
1
1.41
1.73
2
2.24
2.45
2.65
2.83
3.16
3.46
-0.301
0
0.301
0.477
0.60
0.7
0.78
0.85
0.9
1
1.1
9.28
16.13
23.51
27.79
30.43
35.73
37.01
40.69
45.32
51.87
58.15
0.97
1.21
1.37
1.58
1.48
1.55
1.57
1.61
1.66
1.72
1.77
1.96
1.92
1.88
1.86
1.84
1.81
1.8
1.77
1.73
1.68
1.62
4.49
4.38
4.24
4.18
4.11
4.02
3.98
3.9
3.79
3.63
3.46

101
Results
Table 3.38: Release parameters of optimized formulation PC2

Zero Order
r2
K0
(h-1)
0.9706 3.9608
First Order
Higuchi
r2
K1
0.9886
(h-1)
0.063
r2
Korsmeyer-
Hixson-
Peppas
Crowell
KH
r2
r2
(h-1/2)
value
0.9901 16.9 0.984 0.5146
(h-1/3)
0.989 0.0835
13
(B) First order model

102
KHC
Results
(C) Higuchi model
(D) Hixon Crowell model
(E) Korsmeyer-Peppas
Fig 3.29: Release kinetics for formulation PC2

103
Results
Table 3.39: Release kinetics of formulation H
S.
No.
Time
(hrs)
1
2
3
4
5
6
7
8
9
10
11
0.5
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
10
12
Square
root
time
(hrs)
0.71
1
1.41
1.73
2
2.24
2.45
2.65
2.83
3.16
3.46
Log
time
(hrs )
Cumulativ
e
% drug
release
8.12
14.63
19.52
25.44
30.05
35.43
38.94
42.22
50.68
57.37
59.68
-0.301
0
0.301
0.477
0.60
0.7
0.78
0.85
0.9
1
1.1
Log
cumulativ
e % drug
release
0.91
1.17
1.29
1.40
1.48
1.55
1.59
1.62
1.7
1.76
1.47
Log
cumulative
% drug
remaining
1.96
1.93
1.91
1.87
1.84
1.81
1.78
1.76
1.7
1.63
1.61
Cube root
cumulative
% drug
remaining
4.51
4.4
4.32
4.21
4.12
4.01
3.94
3.86
3.68
3.49
3.43
Table 3.40: Release parameters of optimized formulation H

Zero Order
First Order
Higuchi
r2
K0
(h-1)
r2
K1
(h-1)
r2
KH
(h-1/2)
0.9736
4.5956
0.9893
0.0727
0.9991
19.568
KorsmeyerPeppas
r2
n
value
Hixson-Crowell
r2
KHC
(h-1/3)
0.9928
0.9857
0.0975
0.6448

104
Results
(B) First order model
(C) Higuchi model
(D) Hixon Crowell model

105
Results
(E) Korsmeyer-Peppas
Fig 3.30: Release kinetics for formulation H
3.3.4.E Comparative in-Vitro Drug release Study of Theophylline after 12 hrs

from Optimized Formulations with the Help of Statistical Analysis (One Way
ANOVA)
Table 3.41: ANOVA
Source
of Sum
of Degree of Mean sum Calculated
information squares
freedom
of squares F value
Between the
formulation
3.92
2
1.96
1.16
With in the
formulation
7.08
6
1.18
Total
11
8

106
Table value
of F
F2, 6 =
5.14
at 5 % level
of
significance
Results
Interpretation: - The calculated F value (1.16) is less than that of table value (5.14)
at 5 % level of significance ( = 0.05). So Null hypothesis was accepted. There was
no significance difference between the % drug released from different optimized
formulations.
3.3.4.F. Stability Study: - Stability study was conducted on only optimized

formulations. The formulation were packed in the aluminium foil and subjected to
stability studies at different temperature and humidity conditions as per the ICH
guidelines viz room temperature (250 C/60% RH) and 400C / 75%RH. The sample
was withdrawn at time intervals of 0, 15, 30 days. The sample was evaluated for
possible weight variation, drug contents, floating lag time and in vitro release profile.
Table 3.42: Physical characteristics of theophylline floating matrix tablet of
batch DPC2 kept at room temperature for 30 days
Physical
parameters
Weight gain (mg)
Percentage drug
content
0 days
791.23 1.44
98.940.51
Batch code DPC2

15 days
791.221.13
99.930.62
30 days
791.241.49
99.810.52
Table 3.43: In-vitro release data of theophylline from floating matrix tablets of
batch DPC2 in 0.1N HCL kept at Room temperature 30 days
S.No.
Time
(hrs)
Absorb
.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
0.5
1
2
3
4
5
6
7
8
10
12
0.107
0.192
0.271
0.312
0.367
0.412
0.461
0.514
0.559
0.643
0.713
Concentration (mg)
ml
0.019
0.035
0.049
0.057
0.068
0.076
0.084
0.095
0.103
0.118
0.131
5 ml
0.09
0.17
0.24
0.28
0.34
0.38
0.42
0.45
0.51
0.59
0.65
900 ml
17.1
31.5
44.1
51.3
61.2
68.4
75.6
85.5
92.7
106.2
117.9
Cum. drug
release
% Cum.
drug release
17.1
31.59
44.37
51.82
62.0
69.54
77.12
87.44
95.17
108.89
121.39
8.55
15.80
22.19
25.91
31.0
34.76
38.56
43.72
47.56
54.45
60.7

107
Results

batch PC2 kept at room temperature for 30 days
Physical
parameters
Weight gain (mg)
Percentage drug
content
0 days
792.392.14
99.511.62
Batch code PC2

15 days
792.412.19
99.411.61
30 days
7922.46
99.291.21
batch PC2 in 0.1N HCL kept at room temperature 30 days
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Time
(hrs)
0.5
1
2
3
4
5
6
7
8
10
12
Absorb
.
0.114
0.196
0.238
0.331
0.364
0.435
0.459
0.471
0.538
0.613
0.681
Concentration (mg)
ml
0.021
0.036
0.052
0.061
0.067
0.080
0.085
0.099
0.086
0.0113
0.125
5 ml
0.105
0.180
0.262
0.305
0.335
0.400
0.425
0.43
0.495
0.565
0.625
Cum. drug
release
900 ml
18.9
32.4
46.8
54.9
60.5
72.2
76.5
77.44
89.1
101.7
112.5
% Cum.
drug release
18.9
32.51
47.09
55.45
61.15
73.27
78.08
79.41
91.54
105.2
116.0
9.45
16.26
23.55
27.73
30.57
36.64
39.04
39.7
45.77
52.60
58.0

batch H kept at room temperature for 30 days
Physical
parameters
Weight gain (mg)
Percentage drug
content
0 days
792.192.18
99.341.19
Batch code H
15 days
732.132.25
99.171.29
30 days
732.112.11
99.131.37
batch H in 0.1N HCL kept at room temperature 30 Days
S.No.
1.
2.
3.
4.
5.
Time
(hrs)
0.5
1
2
3
4
Absorb.
0.093
0.171
0.234
0.305
0.353
Concentration (mg)
ml
0.017
0.035
0.043
0.056
0.065
5 ml
0.08
0.17
0.21
0.28
0.32
Cum. drug
release
900 ml
15.3
31.5
38.7
50.4
58.5
15.8
31.58
38.96
50.87
59.25

108
% Cum.
drug release
7.65
15.69
19.48
25.43
29.63
Results
6.
7.
8.
9.
10.
11.
5
6
7
8
10
12
0.425
0.461
0.498
0.599
0.678
0.704
0.078
0.085
0.091
0.110
0.125
0.129
0.39
0.42
0.45
0.55
0.63
0.64
70.2
76.5
81.9
99.0
112.5
116.1
71.28
77.97
83.79
101.35
115.4
119.63
35.62
38.98
41.89
50.67
57.7
59.87

batch DPC2 kept at 400C / 75 % RH for 30 days
Physical
parameters
Weight gain (mg)
Percentage drug
content
0 days
793.161.97
98.920.21
Batch code DPC2

15 days
794.131.82
98.640.39

109
30 days
794.911.13
98.310.68
Results
batch DPC2 in 0.1N HCL kept at 400 C/ 75 %RH for 30 Days
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Time
(hrs)
0.5
1
2
3
4
5
6
7
8
10
12
Absorb
.
0.109
0.191
0.269
0.308
0.361
0.415
0.467
0.514
0.563
0.641
0.715
Concentration (mg)
ml
0.02
0.035
0.049
0.056
0.066
0.076
0.086
0.095
0.104
0.118
0.132
5 ml
0.1
0.17
0.24
0.28
0.33
0.38
0.43
0.47
0.52
0.59
0.66
Cum. drug
release
900 ml
18.0
31.5
44.1
50.4
59.4
68.85
77.4
85.5
93.6
106.2
118.8
% Cum.
drug release
18
31.6
44.37
50.92
60.19
69.98
79.81
87.44
96.02
109.14
122.3
9
15.8
22.18
25.46
30.09
34.99
39.91
43.72
48.01
54.57
61.16

batch PC2 kept at 400C /75 % RH for 30 days
Physical
parameter
Weight gain (mg)
Percentage drug
content
0 days
792.461.23
99.640.12
Batch code PC2

15 days
793.111.14
99.50.31
30 days
793.581.41
99.290.49
batch PC2 in 0.1N HCL kept at 400 C/ 75 % RH for 30 Days
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Time
(hrs)
0.5
1
2
3
4
5
6
7
8
10
12
Absorb.
0.112
0.191
0.281
0.327
0.361
0.431
0.459
0.465
0.531
0.601
0.681
Concentration (mg)
ml
5 ml
900 ml
0.021
0.11
18.9
0.35
0.17
31.5
0.052
0.26
46.9
0.060
0.30
54.0
0.66
0.33
59.4
0.079
0.39
71.1
0.085
0.42
76.5
0.086
0.43
77.4
0.097
0.49
88.2
0.111
0.55
99.9
0.126
0.63
113.4
Cum. drug
release
18.9
31.61
47.08
54.54
60.24
72.27
78.07
79.39
90.62
102.81
116.86

110
% Cum.
drug release
9.45
15.81
23.54
27.27
30.12
36.14
39.03
39.69
45.31
51.4
58.43
Results
batch H kept at 400C 75 % RH for 30 days
Physical
parameter
Weight gain (mg)
Percentage drug
content
0 days
734.141.84
99.120.59
Batch code H
15 days
734.141.98
98.910.56
30 days
7351.24
98.120.51
batch H in 0.1N HCL kept at 400 C/ 75 %RH for 30 Days
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Time
(hrs)
0.5
1
2
3
4
5
6
7
8
10
12
Absorb.
0.091
0.173
0.234
0.305
0.351
0.427
0.457
0.496
0.569
0.679
0.707
Concentration (mg)
ml
5 ml
900 ml
0.017
0.085
15.3
0.32
0.16
28.8
0.043
0.22
38.7
0.056
0.28
50.4
0.065
0.32
58.5
0.079
0.39
71.1
0.084
0.42
75.6
0.091
0.45
81.5
0.104
0.52
93.5
0.125
0.62
112.5
0.13
0.65
117.0
Cum. drug
release
15.3
28.88
38.95
50.86
59.24
72.16
77.05
82.77
95.49
115.35
120.41
% Cum.
drug release
7.65
14.44
19.47
25.43
29.62
36.08
38.53
41.88
47.74
57.67
60.24
4.1. PREFORMULATION PARAMETRS

4.1.1. Study on Drug
Table 4.1: Results and discussion of preformulation parameters of drug
S.No.
1.
Parameters
Physical characters
2.
Identification
Physical method
(a) Xanthine test
(b) Melting Point
(c) Loss on drying
(d) Hygroscopicity
Analytical method
(a) max
Results
Crystalline powder, white,
Odorless, Bitter
Positive
2700C
0.399 %
0.07 %(room temp)
0.16 %(400C/75%RH )
Conclusion
On the bases of
these tests it
could be confirm
that the drug
sample was pure
and authentic.
270 nm (0.1 N HCL)

263 nm (0.1N Methanolic HCL)
274 nm (0.1 N NaOH)

111
Results
(b) I R spectra
(c) Rf
(d) Assay
Solubility Analysis
Showed all characteristics peaks

0.67
99.185 %
In different solvents
(a) Water
(b) 0.1 N HCL
(c) 0.1 NaOH
(d) Ethanol
120.98
37.39
20.9
296.73
In different pH
(a) 1.2 (0.1N HCL
(b) 3.5
(c) 5
(d) 7
(e) 8
26.74 (mg /ml)

23.71 (mg /ml)
17.90 (mg /ml)
8.27 (mg /ml)
12.84 (mg /ml)
5.
Micromeritics
(a) Carrs index
(b) Angle of repose
(c) Hausner Ratio
Particles Size Range
27 %
310
1.36
10- 150 micrometer
6.
Partition Coefficient
-0.666 (log p)
7.
Ionization Constant
8.7 and 11.47
8.
Drug Polymer Interaction

Study
No change in Rf valve
4.
Slightly soluble
Sparingly soluble
Soluble
Slightly soluble
Indicates
solubility slightly
increase as pH
increase,
otherwise it is
independent
of
pH
Passable flow
Fine and very
fine
Indicates more
hydrophilicty
than lipohhilicity
Indicates weak
acidic & weak
basic drug
Indicates no
interaction
4.1.2. Study on Psyllium Husk

Table 4.2: Results and discussion of psyllium husk parameters
S.No.
Parameters
1.
Physical Characters
2.
3.
4.
Test for Mucilaginous Matter

pH (1% aqueous Sol.)
Ash Value
(a) Total Ash
(b) Acid-insoluble Ash
Results
Husk psyllium
Powder of psyllium
seed, Pale buff color,
odorless, Test less
Positive
6.85
Dehusk psyllium
Powder of psyllium
seed, Pale buff color,
odorless, Test less
Positive
6.85
3.52 %
0.75 %
3.52 %
0.75 %

112
Results
5.
6.
7.
8.
9.
10.
11.
12.
Extractive Values
(a) Alcohol-soluble extractive
(b) Water soluble extractive
Loss on Drying
Hygroscopicity
(a) Room temp
(b) 400 C/ 75 % RH
Swelling Factor (after 12 hrs)
True Density
Viscosity
Micromeritics
(a) Carrs index
(b) Angle of Repose
(c) Hausner Ratio
Particle Size Distribution
5.68 %
5.68 %
7.14%
2.597 %
7.14%
3.68 %
No weight gain
No weight gain
6.5 %
46 ml
0.998 g/cc
370 cps
7.43 %
42.5 ml
1.086 g/cc
365 cps
13.38
Indicates
25.87
the good
1.15
flow
130-250 micrometer
15.2
Indicates
27.17
the good
1.16
flow
1-120 micrometer
Conclusion: - On the bases above tests, it could be confirm that the psyllium husk
sample was pure and authentic. In the present dissertation work, floating matrix
tablets of theophylline were prepared using the polymers psyllium husk (dehusk and
husk grades) and HPMC K 100 M. The tablets were prepared by using the sod.
Bicarbonate as gas generating agent. The fabricated tablets were evaluated for their
physical characteristics such as weight variation, content uniformity, floating
capabilities, effect of hardness on buoyancy, swelling properties, erosion study and in
vitro release study.
4.2.1 Thickness: - The Thickness of the tablets was found to be 5.54 0.73 mm
(batch DP1) to 6.59 0.13 73 mm (batch DP7) for the formulations prepared with
dehusk psyllium and 5.560.73 73 mm (batch P1) to 6.610.21 73 mm (batch P7) for
the formulations prepared with husk psyllium. The thickness of formulation prepared
with HPMC K 100 M alone was 6.410.47 (batch H) and combination with psyllium
was 6.480.37 (batch DPH) &. 6.50.18 (batch PH). The thickness of the optimized
formulation was found to be 6.790.73 (batch DPC2) and 6.970.14 (batch PC2).
4.2.2 Hardness: - Several authors (Ford et al., 1985.and Dahl et al., 1990) have
stated that the compression force is a statistically significant factor in the tablets
hardness. It could be assume that the variation in the compression force is closely

113
Results
related to change in the porosity of the tablet. However as the porosity of the hydrated
matrix independent of initial porosity. Nikhodchi et al., (1996) concluded the
compression force seem to have a little effect on the drug release.
All formulation was prepared with the help of PVP (5 % in IPA). The hardness of the
formulation prepared from dehusk psyllium was found to be vary in between 2.5
0.52 (batch DP1) to 2.83 0.32 (batch DP 7). The hardness prepared with husk
psylluim was slightly less than that of dehusk husk. This is due to larger particle size
of husk psyllium. The hardness of the husk psyllium was found to be in between vary
2.130.36 (batch P1) to 2.73 0.42.
The hardness of the formulation prepared with HPMC K 100 M was found to be
4.20.4
(batch H) and combination with dehusk and husk psyllum powder were found to be
3.90.26 (batch DPH) and 3.16 0.15 (batch ph) respectively.
4.2.3 Friability: - The friability of the formulations prepared with husk psylluim
husk was greater than that of dehusk psyllium. The Friability of the formulation
prepared with HPMC K 100 M was lowest (batch H 0.51 0.087). The friability of
the optimized formulations was found to be 0.710.089 (batch DPC2) and .750.091
(batch PC2).
The friability of the all formulations was found to be with in the limits i.e. 0.5 % - 1%
4.2.4 Content Uniformity: - The content uniformity was determined in 0.1 N HCL.
The drug content of all preparation was found to be in the range 95%-105%. No
tablets were found out of this range. This ensures the uniformity in drug content in the
different batches.
4.2.5 Weight Variation: - Weight variation of the prepared floating matrix tablets
indicating that there was no significant difference in the weight of the individual
tablets from the average valve. As per the USP specification no tablet deviate from the
average weight by more than 5.

114
Results
4.2.6 Floating Capabilities: - The floating capabilities mainly concern here with
floating lag time and floating duration.
The floating duration should be at least 24 hrs and the floating lag time should be as
low as possible because complex anatomy and physiology of GIT. The fasted state is
associated with various cyclic movement commonly referred as migrating motor
complex (MMC).The third phase of MMC (burst phase) is characterize by the large,
intense and regular contraction termed as house keeper waves that swept out the
particulate matter (undigested food particles) from the stomach and lasts to 10to 20
minutes. To prevent the formulation from the effect of this phase, tablet should be
float as fast as possible after reaching in the stomach.
In similar way the floating duration and dimensional stability are important in case of
once daily formulation obtain the continuous and constant drug release up to the 24
hrs.
If physical integrity of the formulation is note maintain, the tablet could break down
in to the small fragments and escape from the upper part of GIT.
4.2.6.A Effect of Psyllium Husk on Floating Capabilities: - The floating lag time
of formulation PD1 containing 200 mg of dehusk psyllium was 3478.69 seconds.
This formulation was not able to maintain the dimensional stability upto the require
time (24 hrs) and duration of floating was 11.30.25 hrs. As the concentration of the
dehusk psyllium increased from 200 to 400(1: 2 drug: polymer ratio) the floating lag
time reduced to 102. 2.56 (batch DP3) and floating duration and dimensional
stability both were maintained more than 24 hrs.
Similar effect were observed with husk psyllium in similar ratio of the drug and
polymer but the floating log time was more than that of dehusk psyllium formulation.
The floating lag time of formulation P3 containing 400 mg (1:2 drug: polymer) of
husk psyllium was 120 2.52 seconds as compared to dehusk psyllium formulation
PD3 (102. 2.56 seconds).
This was due to grater particle size of husk psyllium as compared to dehusk psyllium
which hydrate at the slow rate and take more time to swell. This result in increasing
the floating lags time.

115
Results
4.2.6.B Effect of Sod CMC on Floating Capabilities: -The Sodium CMC was
added to reduce the floating lag time. Formulation containing 50 mg sodium CMC
had the floating lag time 78 1.93 and the formulation containing 100 mg of sodium
CMC had 71 3. The reduction of the floating lag time is due to sodium CMC is a
synthetics agent which hydrated at a faster rate than that of psyllium husk.
Similar effect was observed with husk psyllium powder. The floating lag time
containing husk psyllium along with 50 mg (batch P4) and 100 mg (batch P5) was
found to be 85.75.03, 79.31.53 respectively.
There was no measurable effect of concentration Sod CMC on floating duration and
dimensional stability.
4.2.6.C Effect of Sodium Bicarbonate on Floating Capabilities: - The floating lag

time reduced as the concentration of sodium Bicarbonate increased in both cases i.e.
dehusk and husk formulations.
Table 4.3: Effect of sod bicarbonate on floating lag time

S.No
1.
2.
3.
Conc. of
sodium
bicarbonate
(%)
10
15
20
Dehusk formulation
FC
FLT
Husk formulation
FC
FLT
DP6
DP4
DP7
P6
P4
P7
982.51
781.93
60.72.52
1055.29
85.75.03
69.72.08
FC = Formulation code, FLT = Floating lag time

The concentrations of sodium Bicarbonate effect the duration of floating in both cases
i.e. dehusk and husk formulation. The duration of floating was 220.61hrs (batch
DP6) with 10 % sodium Bicarbonate and 24 hrs (batch DP4, DP7) when the
concentration of sodium Bicarbonate was 15 % (batch D P4) and 20 %.( batch DP7).
In case of husk the duration of floating was 20.20.85hrs (batch P6) with 10 %
sodium Bicarbonate and 24 hrs when the concentration of sodium Bicarbonate was 15
% (batch P4) and 20 %.( batch P 7).This might de due to the gas generated by 10 %
sodium Bicarbonate might not be sufficient to keep the formulation in floating state
for prolonged period of time (24 hrs) where as the in case of 15 %, 20 % sodium

116
Results
Bicarbonate sufficient gas produced to keep the formulation in floating state for 24
hrs.
The concentration of sodium Bicarbonate oppositely effect the dimensional stability
but this effect was not significant.
4.2.6.D Effect of Ac- Di Sol on Floating Capabilities: - Ac- Di Sol is a super

disintegrate when it come in contact with the medium swell rapidly at least two times
of its original volume. The psyllium husk and sodium Bicarbonate simultaneously
form the gel network due to which the swell mass of Ac-Di-Sol is retaining in the gel
and tablet does note disintegrate.
The additional advantage of it, the maximum water uptake is achieved in short period
of time as the water reach in the deep in to the core of the tablet.
Being a disintegrate Ac-Di-Sol creates the pores and the CO 2 generated with the
reaction of Sodium Bicarbonate and acidic medium was entrapped in the pores
resulting the floatation of the tablets i.e. the log time further reduced.
5 % and 10 % of Ac-Di-Sol were used. The formulation containing 10 % Ac-Di-Sol
(batch DPC2, 45 2 seconds) take less time to float as compared to the formulation
containing 5 % Ac-Di-Sol (batch DPC1, 55.1 1.53 seconds) in the case dehusk
psyllium. Similar effect was observed with formulation containing husk psyllium.
Formulation containing HPMC K 100 M showed very short lag time (batch H, 10.3
1.53 seconds) without sod CMC and Ac-Di-Sol.
4.2.6.E Effect of Hardness on Floating Capabilities: - As the hardness increased

the floating lag time also increased. On immersion of tablets (batch DPC2, PC2, H )
of hardness around 2 kg/ cm2 in 0.1 HCL solution floated immediately 45.11.53
seconds for DPC2, 501.63 seconds for PC2, zero for H ) as compared to the
formulation 4 kg/ cm2 took more time ( 190 5 seconds for DPC2, 2008 seconds for
PC2,10.3 1.53 seconds H) to come up to the surface. The tablets hardness 6 kg/cm 2
showed the no floating in case of dehusk formulation and husk formulations while the
formulation containing HPMC Float in 90 7.5 seconds.
In fact, buoyancy of the tablet is governed by both the swelling the outer surface of
the tablets when it comes in the contact with the gastric fluids, and the presence of the

117
Results
internal void (Porosity) in the dry centre of the tablet. These two factors are essential
for the tablet to acquire bulk density less than that of the gastric fluid i.e. 1.04 gm/cm 3
which helps them to remain buoyant on gastric fluids (sheth and tossoumnian, 1979)
Compression force of these tablets to high degree hardness may result in reduction of
porosity of the tablets and moreover, the compressed hydrocolloids particle on the
surface of the tablets fail to hydrate rapidly when the tablets come in to contact with
the gastric fluid, and as a result of this, the capability of the tablets to float is
significantly reduced.
4.2.7 Density: - The density of the formulation should be less than that of 1.04
kg/cm3 (Chues et. al. 1990).
The density of all the formulation was in the range of 0.792 0.085 to 1.047 0.024
for all formulation.
4.2.8 Swelling Index: - Baumgartner et al. (1998) Concluded that tablets composed
of polymeric matrices build a gel layer around the tablet core when they come in
contact with water This gel govern the drug release. Kinetics of swelling is important
because the gel barrier is formed with water penetration. Swelling is a vital factor to
ensure floating. To obtain floating, the balance between the swelling and water must
be reported.
As shown in table the formulation containing psyllium husk (both grades dehusk and
husk psylluim) took about 6 to 8 hrs to complete swell as compared to the formulation
prepared with HPMC k100 M that took 4-5 hrs to complete swell.
In the first hr of study, the swelling index of formulation DP3 was 57.1 % (dehusk
psyllium), P3 was 46.03 % (husk psyllium), and H was 85.92 % (HPMC K 100 M)
The difference in the swelling index was because of the psyllium husk is a natural
agent took more time to hydrate as compared to synthetic agent HPMC K 100 M.
The difference in the swelling index between the formulation prepared with husk and
dehusk psyllium was due to the difference in the particle size. The particle size of
husk psyllium powder was grater than that of the dehusk psyllium resulting the
delayed the hydration.

118
Results
After complete swelling the formulation prepared with husk psyllium (P3 348.15 %)
showed the grater-swelling index than that of dehusk psyllium (Batch DP3, 334.9 %),
this was due to presence of husk in husk psyllium, which enhance the swelling index.
Addition of Sod .CMC enhanced the swelling index at initial stage (batch DP4 70.9
%, batch P4 58.9%) due to faster rate of hydration as compared to psyllium powder.
The formulation prepared with sod .CMC and Ac- Di Sol showed the swelling index
after first hr of study was 78.14 % (batch DPC2), 65.12 % (batch PC2) due to he
grater efficiency Ac- Di Sol for water and faster hydration.
4.2.9 Erosion Study: -The tablets containing the husk psyllium showed the higher
erosion after 12 hrs (9.25% batch P3) than that of formulation prepared with dehusk
psyllium (7.49% batch DP3). Addition of Sod CMC reduced the erosion in both
formulation prepared with husk (6.97 % batch P4) and dehusk psylluim (5.87 % batch
PD4).
Formulation containing Ac-Di-Sol further reduced the percent erosion (4.95 % DPC2,
5.01 % batch PC2) than that of formulation prepared with psyllium alone (7.49%
batch DP3 9.25% batch P3) or in combination with sod CMC (5.87 % batch PD4,
6.97 % batch P4)
The formulation containing pure HPMC K 100 M showed the lowest erosion among
all the preparation.
4.2.10 In-Vitro Release Study

4.2.10.A Effect of Psyllium Husk on In-Vitro Release: - The formulation DP1
(dehusk psylluim) and P1(husk psyllium) (200 mg psyllium husk, 1:1 drug :polymer)
the burst release after 2 hrs was 335.51and 37.92 and final release after 12 hrs was
82.22 and 80.72 respectively. But these formulations were not able to maintain the
dimensional stability and the drug release was note up to 24 hrs. So the amount of
psyllium was increased to 300mg (1:1.5 drug: polymer) and 400 mg (1:2, drug:
polymer). The burst release after 2 hrs was 24.19 (DP2), 29.39 (P2) for the
formulation containing 300 mg of psyllium husk and 20.79 (DP3), 25.42 (P3) for the
formulation containing 400 mg of psyllium husk. Final % cumulative drug release
after 12 hrs 66.23 (DP2), 57.56 (P2) for the formulation containing 300 mg of
psyllium husk. and 47.89 (DP3) and 4.58 (P3) for the formulation containing 400 mg

119
Results
of psyllium husk. This might be due to gelling property of psyllium husk. As the
concentration of psyllium husk incased resulting in increased the gel concentration,
which lead to increased the diffusion pathway and thus decreased the diffusion rate,
which decreased the release of the drug, and complete release was obtained in 24 hrs.
The burst release of formulation prepared with hush psyllium was slightly more than
that of dehusk .It was due to larger particle size of husk psyllium than that of dehusk
psyllium which took more time to hydrate than that of dehusk.
The total % cumulative drug release after 12 hrs from dehusk psyllium formulation
was slightly more than that of husk psyllium formulation. It was due to the presence
of
husk in hush psyllium, which provides an additive effect in swelling resulting
slightly reduction in drug release.
(A) Husk psyllium

120
Results
(B) Dehusk psyllium

Fig 4.1: Effect of psyllium husk on In- vitro drug release
4.2.10.B Effect of Sodium CMC on In-Vitro Release: - Two quantity of the

sodium CMC (50 &100 mg) were used in both grades of psyllum husk.
There was no significant effect on the drug release but the burst release after 2 hrs was
reduced. The reason behind it faster rate of hydration of sodium CMC than psyllium
husk..
The % burst release of after 2 hrs for formulation containing sodium CMC was 20.14
(batch DP4, dehusk psylluim), 22.70 (batch P4, husk psyllium) than that of the
formulation with out sodium CMC 22.79 (batch DP3) and 25.42 (batch P3).

121
% Cum. Drug release
Results
P3
P4
60
50
40
30
20
10
0
P5
5
10
Time (hrs)
15
% Cum . Drug release
(A) Husk psyllium
DP3
60
50
40
30
20
10
0
DP4
DP5
10
15
Time(hrs)
(B) Dehusk psyllium

Fig 4.2: Effect of Sod. CMC on invitro drug release
4.2.10.C Release from the Formulation Containing HPMC K 100 M: - To

compare the release pattern of the psylluim (both grades), separate formulation
containing HPMC K 100 M was prepared in 1: 2 ratio of drug and polymer.
The initial % burst release after 2 hrs with HPMC K100 M was 19.52 (batch H) which
was less than that of preparation prepared with psyllium powder (batch DP4 -20.14
batch P4- 22.7). The % cumulative drug release after 12 hrs was 59.47 (batch H),
49.47 (batch DP4) and 46.89 (batch P4).

122
Results
Initial burst release in case of HPMC K100 M was low than that of psyllium due to
faster rate of swelling of HPMC K100 M. After 12 hrs release of drug from HPMC
was more than that of formulation prepared with psyllium because the swelling index
of psyllium was more than that of HPMC K100 M.
Fig 4.3: Effect of HPMC K 100 M on invitro drug release
4.2.10.D Effect of Cross Povidone on In-Vitro Release: - In order to improve the

release profile of formulation prepared with psyllum husk as parallel to HPMC K100
M the cross povidone was used.
Formulation containing 0 % of Ac-Di-Sol showed the cumulative % drug release
49.47 (batch DP4), 46.89 (batch P4) and formulation containing 5% Ac-Di-Sol
showed the cumulative % drug release was 55.27 (batch DCP1), 52.04 (batch PC1).
Formulation containing 10% Ac-Di-Sol showed the cumulative % drug release was
60.01 (batch DCP2), 58. 15 (batch PC2) which was comparable to formulation
prepared with HPMC K 100 M (batch H, 59.47).
The reason behind it Ac-Di-Sol is a super disintegrate and creates pores in the net
work form by psyllium and sod.CMC.due to which the release of the drug increased
in the latter hrs.

123
% Cum . Drug release
Results
P4
PC1
PC2
70
60
50
40
30
20
10
0
0
10
15
Tim e(hrs)
% Cum Drug release
(A) Husk psyllium
DP4
DPC1
DPC2
70
60
50
40
30
20
10
0
0
5
10
Time(hrs)
15
(B) Dehusk psyllium

Fig 4.4: Effect of Ac-Di-Sol on invitro drug release
4.2.10.E Effect of Sod Bicarbonate on In-Vitro Release: - Sodium bicarbonate

showed the opposite effect on percentage cumulative drug release. This might be due
to the alkaline nature of the sodium bicarbonate, which create an alkaline environment
around the tablet. Theophylline was less soluble in the alkaline environment that
decreased the release of drug from the formulation. Formulation containing 10 %
NaHCO3 shown the drug release after 12 hrs was 51.42 (batch DP6), 48.39 (batch
P6) as compared to formulation 20 % NaHCO3 the drug release after 12 hrs was
47.77 (batch DP7), 45.55 (batch P7)

124
Results
(A) Husk psyllium
(B) Dehusk psyllium

Fig 4.5: Effect of sod. bicarbonate on invitro drug release
4.2.10.F Effect of Agitation on In-vitro Drug Release: -This study was conducted
only on optimized formulation like DPC2 (dehusk), PC2 (husk), H (HPMC K 100M).
At 50 rpm cumulative percentage drug release after 12 hrs was formed to be 57.26
(DPC2), 56.71 (PC2), 58.21 (H).
At 100 rpm cumulative percentage drug release after 12 hrs was 60.01 0.99 (DPC2),
58.15 (PC2), 59.47 (H).
The release of drug was slightly higher at 100 rpm, since the delivery by diffusion
mechanism occurred through the gel layer, the system is mainly based on this release
mechanism get effected by stirring.(FIG. 4.6)

125
Results
(A) DPC2
(B) PC2
(C) H
Fig 4.6: Effect of RPM on invitro drug release
4.2.11. Release Kinetics: - The In-vitro release data of optimized formulations were
treated with different kinetics models to explain the release kinetics of theophylline
from floating matrix tablets. These models were zero order, first order, higuchi model,
hixon-crowel model and korsemayer peppas model. Higuchi model was considered as
the best fitted model with the highest value of correlation coefficient (r2). The value

126
Results
r2 of different optimized formulation DPC2, PC2, H were found to be 0.997, 0.9901,
and 0.9991 respectively.
The release data were further treated by Ritger-Peppas or power law to calculate the
value of n (release exponent). The values of n (release exponent) for different
optimized formulations were found to be 0.5422 for DPC2 (dehusk psyllium), 0.5146
for PC2 (husk psyllium), and 0.6448 for H(HPMC K 100 M). The value of n indicate
that the release mechanism from different formulation was the non-fickian diffusion
(anomalous type), controlled by the diffusion through swollen matrix.
4.2.12. Drug Polymer Interaction Study on Optimized Formulation: - Drug and

polymer interaction in the optimized formulation was checked with the help of TLC
and FT-IR study.
TLC data showed that there was not a significance difference in the Rf value. FT-IR
data also showed that the characteristics peaks of drug of were observed in the FT-IR
Spectra of formulation prepared with Psyllium husk (DPC2 & PC2) and HPMC K
100 M.
4.2.13. Statistical Analysis: - Analysis of variance (ANOVA) was applied to

identify the significance difference in percent drug release of various formulation
prepared by psylluim powder (husk and dehusk psylluim) and HPMC K 100 M.
ANOVA interpretation showed there was no significance difference in % cumulative
percent drug release of formulation prepared with dehusk psyllium, husk psylluim and
HPMC K 100M at 5 % level of significance ( = 0.05).
4.2.14. Stability Studies: - The optimized formulation was subjected to stability

studies at a room temperature and 400C / 75% RH. These formulations were evaluated
for their appearance possible weight gain in drug content and in-vitro release study.
Negligible change was seen in different physicochemical parameters at a room
temperature as well as 400C/75 % RH. There was no significance difference in invitro release and in content uniformity after one month stability study at both room
temperature and accelerated conditions.

127

Result and Discussion 6

Diunggah oleh

Informasi Dokumen

Deskripsi Asli:

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Result and Discussion 6

Diunggah oleh

Hak Cipta:

Format Tersedia

Results

RESULT AND DISCUSSION

was determined with Roche friabilator apparatus

(Hicon, India). Following formula was used to determination of friability:

(Initial wt - Final wt / Initial wt ) 100

Table 3.2: Average hardness and friability

Average hardness (kg/cm 2)

Average friability (%)

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Average Weight (mg)

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Total amount of drug = 200 mg, dilution factor = 10 slope = 0.0543

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Total amount of drug = 200 mg, dilution factor = 10 slope = 0.0543

% Cum. drug release

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Total amount of drug = 200 mg, dilution factor = 10 slope = 0.0543

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration in (mg)

% Cum . drug release

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Dept. of Pharmaceutical Sciences S.S.I.T.M.

% cum . drug release

Fig 3.8: In-Vitro release of theophylline from batch P1 in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Fig 3.9: In-Vitro release of theophylline from batch P2 in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

%Cum . drug release

Fig 3.10: In-Vitro release of theophylline from batch P3 in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

%Cum. drug release

Fig 3.11: In-Vitro release of theophylline from batch P4 in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Fig3.12: In-Vitro release of theophylline from batch P5 in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Fig 3.13: In-Vitro release of theophylline from batch P6 in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

% Cum. drug release

Fig 3.14: In-Vitro release of theophylline from batch P7 in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Fig 3.15: In-Vitro release of theophylline from batch H in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Fig 3.16: In-Vitro release of theophylline from batch DP H in 0.1N

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)

Fig 3.17: In-Vitro release of theophylline from batch P H in 0.1N HCL

Dept. of Pharmaceutical Sciences S.S.I.T.M.

Absorb Concentration (mg)