DESIGN AND INVITRO CHARACTERIZATION OF GASTRO RETENTIVE FLOATING TABLET CONTAINING GLICLAZIDE

1. “DESIGN AND IN-VITRO
CHARACTERIZATION OF GASTRORETENTIVE
FLOATING TABLET CONTAINING
GLICLAZIDE”
By
Joshi Deepak Annarao ( M.pharm )
(12PU287)
Under the supervision of
Mr. S. M. Chickpetty M.Pharm (PhD)
Dept. of Pharmaceutics,
K.R.E.S’s Karnataka College of Pharmacy,
Bidar, Karnataka

2. NEED FOR THE STUDY
 Gliclazide is an effective oral antidiabitic agent of Sulfonyl urea and is
the drug of choice for management of (Type II) diabetes mellitus.
 It is poorly soluble at alkaline pH, majorly absorbed from the upper
part of the GIT(stomach) and is degraded in the colon.
Therefore, in the present study it was planned to design a
suitable gastroretentive floating tablets of Gliclazide by using polymers
like guar gum and carbopol in combination with HPMC by using
sodium bicarbonate as gas generating agent;
 To prolong gastric residence time (↑duration of action),
 To increase its oral bioavailability.
 To improve patient compliance.
 To reduce drug dose.

3. MAJOR OBJECTIVES OF THE INVESTIGATIONS ARE;
 Preparation of calibration curve of Gliclazide in pH 1.2 buffer.
 To perform drug-excipient compatibility studies by using FTIR.
 To study flow properties of powder materials like repose angle and
Carr’s index.
 To prepare Gliclazide floating tablets by direct compression
method.
 To evaluate designed tablet for various in process quality control
tests like hardness, friability, weight variation etc.
 To perform in-vitro buoyancy studies & Swelling index.
 To perform in-vitro drug release studies in pH 1.2 buffer media.
 To perform stability studies on optimized batches (HG33 and
HC42).

4. Composition of Gastroretentive Floating Tablets Containing
Gliclazide
Ingredient
(mg)
Category
Composition of Gliclazide floating Tablet
C30 C60 C90 G30 G60 G90 HG51 HG42 HG33 HC51 HC42 HC33
Gliclazide
Active
drug
50 50 50 50 50 50 50 50 50 50 50 50
HPMC K15M
Matrix
material
-- -- -- -- -- -- 75 60 45 75 60 45
Carbopole
Release
modifier
30 60 90 -- -- -- -- -- -- 15 30 45
Guar gum
Release
modifier
-- -- -- 30 60 90 15 30 45 -- -- --
Sodium
bicarbonate
Gas
generating
agent
50 50 50 50 50 50 50 50 50 50 50 50
MCC Diluents 90 60 30 90 60 30 30 30 30 30 30 30
Talc Lubricant 03 03 03 03 03 03 03 03 03 03 03 03
Mag.stearate Glidant 02 02 02 02 02 02 02 02 02 02 02 02
HPMC:CP ---- 0:2 0:4 0:6 -- -- -- -- -- -- 5:1 4:2 3:3
HPMC:GG ---- -- -- -- 0:2 0:4 0:6 5:1 4:2 3:3 -- -- --
Total weight (mg) 225 225 225 225 225 225 225 225 225 225 225 225

5. 1 • Weighed
2 • Milled
3
• Screened
METHODOLOGY
PREPARATION OF FLOATING TABLETS
(DIRECT COMPRESSION TECHNIQUE)
4 • Mixed
5
• Compress
6
• Tablet (8mm)

6. EVALUATION OF GLICLAZIDE TABLETS
The developed Gliclazide tablets are evaluated under
following distinct headings;
 Thickness & Diameter
 Hardness
 Friability
 Weight Variation
 Drug Content
 Tablet Density
 In vitro buoyancy studies
 Swelling index
 In vitro Dissolution studies
 Compatability studies by FTIR Studies
 Stabilities studies

7. RESULTS AND DISCUSSION
Standard Calibration curve Gliclazide in pH 1.2 buffer at max 226 nm
Buffer Solution Slope R2 value Intercept
pH 1.2 0.025 0.999 0.00
Linear regression analysis:
The linear regression analysis for standard curve in pH 1.2 was done on
absorbance data points. The results are as follows:
0
0.2
0.4
0.6
0.8
0 5 10 15 20 25
Absorbance(nm)
Conncentration (μgm/mL)

8. Before compression the tablet powder formulations were evaluated for
their flow properties like,
1. Angle of Repose
2. Carr’s compressibility index
Conclusion :
Powder formulation has shown good flow properties and good
compressible characteristics.
TABLET POWDER FLOW PROPERTIES
Parameters Tablet Powder Formulation
Angle of repose () 23.96º – 28.72º (< 29 )
Carr’s Index (%) 12.63 – 17.37 (< 18 )

9. CHARACTERISTICS OF FLOATING TABLET OF
GLICLAZIDE
1.Thickness & Diameter:
 It is performed by using vernier caliper.
Conclusion:
The thickness & diameter of the tablets was found to be uniform
and consistent as indicated by their low SD values in all the batches.
Thickness(mm ± SD) Diameter (mm ± SD)
3.30 ± 0.06 to 3.86 ± 0.18 8.02± 0.01 to 8.16 ± 0.301

10. 2. Weight Variation test:
 It is performed by using single pan electronic balance.
Conclusion:
The average percentage deviation of all batches of the
tablets was found to be within the pharmacopoeial limit (<7.5%),
hence all the tablet formulation passed the test for uniformity of
weight as per official requirements.
Weight Variation (%)
1.64 to 4.08 (< ± 7.5%)

11. 3. Hardness test:
 It is performed by using Monsanto hardness tester.
Conclusion:
This indicates that tablets are of sufficient strength to
withstand the mechanical shock encountered during
packaging ,transportation and handling.
Hardness (kg/cm2 ± SD)
4.43 ± 0.19 to 4.78 ± 0.16

12. 4. Friability test:
 It is performed with the help of Roche Friabilator.
Conclusion:
The friability study shows the percentage friability were
found to be less than 1%, indicating that the friability is within
the limit.
It was understood that the tablets are of sufficient
strength to withstand the stress of transportation.
Friability (%)
0.168 to 0.860

13. 5.Drug Content:
 It is performed by spectrophotometric method.
Conclusion:
The drug content was found to be uniform in the
formulation. This indicates tablets contains claimed amount
of drug.
Drug Content (%)
98.04 ± 1.67 to 101.40 ± 1.31

14. 6. Tablet density:
 It is performed by using following formula.
V = πr2h
d = m/v
v = volume of tablet (cc),
r = radius of tablet (cm),
h = crown thickness of tablet (cm),
m = mass of tablet
Conclusion:
The tablet density of all the formulations was found to be
less than the density of gastric contents. (1.004 g/cm3)
C-bans at 943 cm-1
Density (gm/cm3)
0.640 to 0.753

15. 7. In vitro buoyancy studies :
 It is performed by using beaker containing 0.1 N HCl (200ml)
Conclusion:
The buoyancy studies showed good buoyancy lag time and total
floating time.
Buoyancy Lag Time (Sec) Total Floating Time (h)
16.00 ±4.65 to 121.00 ± 4.39 0.10 ±3.76 to 24.00 ± 0.14

16. 9. Swelling index:
It is performed by using Petri dish containing 0.1 N HCL .
Conclusion:
From the results, it can be concluded that as polymer concentration
increases, swelling index also increases.
Formulation
code
Swelling index (%)
1 hr 2 hr 4hr 6 hr 10 hr 12 hr
C30 Tablet fails to float
C60 Tablet fails to float
C90 Tablet fails to float
G30 Tablet breaks within 10 min
G60 Tablet breaks within 20 min
G90 Tablet breaks within 4 hr
HG51 39 48 71 82 114 112
HG42 43 52 66 79 98 118
HG33 39 51 63 75 97 109
HC51 47 58 69 81 106 131
HC42 45 53 62 77 99 128
HC33 37 47 69 80 93 115

17. 17
COMPRESSIONAL CHARACTERISTICS OF GLICLAZIDE FLOATING
TABLETS
Formulation
Codes
Diameter
(mm ± SD)
Thickness*
(mm ± SD)
Hardness*
(Kg/cm2 ± SD)
Friability
(%)
Drug Content*
(% ± SD)
Weight
Variation (±%)
C30 8.02 ± 0.01 3.86 ± 0.18 4.56 ± 0.25 0.443 98.24 ± 3.16 ± 3.88
C60 8.07 ± 0.07 3.38 ± 0.16 4.63 ± 0.24 0.168 101.4 ± 1.31 ± 2.36
C90 8.03 ± 0.08 3.82 ± 0.23 4.60 ± 0.28 0.610 99.88 ± 1.56 ± 3.26
G30 8.03 ± 0.01 3.64 ± 0.32 4.62 ± 0.20 0.830 101.16 ± 1.052 ± 3.18
G60 8.16 ± 0.30 3.86 ± 0.11 4.43 ± 0.19 0.860 98.04 ± 1.67 ± 3.26
G90 8.03 ± 0.01 3.68 ± 0.19 4.67 ± 0.18 0.386 98.76 ± 1.43 ± 3.48
HG51 8.04 ± 0.03 3.82 ± 0.08 4.66 ± 0.33 0.620 98.68 ± 2.86 ± 3.61
HG42 8.03 ± 0.02 3.68 ± 0.13 4.78 ± 0.16 0.303 100.64 ± 1.37 ± 3.83
HG33 8.08 ± 0.06 3.83 ± 0.28 4.72 ± 0.13 0.616 98.96 ± 2.27 ± 4.08
HC51 8.03 ± 0.01 3.82 ± 0.29 4.76 ± 0.20 0.443 99.36 ± 2.71 ± 3.34
HC42 8.04 ± 0.30 3.82 ± 0.28 4.62 ± 0.30 0.602 98.12 ± 1.56 ±1.64
HC33 8.07 ± 0.07 3.30 ± 0.06 4.70 ± 0.21 0.336 99.64 ± 1.86 ± 3.42

18. CHARACTERISTICS OF GLICLAZIDE FLOATING TABLETS
Formulation
codes
Tablet Density
(gm/cc)
Buoyancy Lag Time
(Sec)
Total Floating Time
( hr)
C30 ---- Fails to float ----
C60 ---- Fails to float ----
C90 ---- Fails to float ----
G30 ---- 29 Dissolves in 10 min
G60 ---- 42 Dissolves in 15 min
G90 ---- 121 4.00
HG51 0.749 16 > 24.00
HG42 0.753 19 16.00
HG33 0.711 30 12.00
HC51 0.751 17 > 24
HC42 0.745 43 13.00
HC33 0.640 53 8.00
*All values are mean (n=3)

19. FTIR spectra of pure drug Gliclazide
↑
5007501000125015001750200022502500275030003250350037504000
1/cm
-15
0
15
30
45
60
75
90
105
%T
3369.75
3273.31
3111.28
2933.83
2868.24
2590.49
2501.76
2434.25
2312.73
2247.15
2171.92
1917.31
1801.57
1693.56
1597.11
1477.52
1344.43
1280.78
1240.27
1155.40
1122.61
1087.89
995.30
912.36
812.06
752.26
705.97
661.61
632.67
563.23
536.23
459.07
435.93
sample C
↑↑ ↑
↑
↑
↑
↑↑
C−H str. 2868.24 and 812.06
C=O str. 1801.57 and 3369.75
N−H str 1597.11 cm-1
C-O-C str 1240.27
C−N str. 1087.89 and 1122.61

20. 20
FTIR spectra of optimized batch HG33 tablet formulation
5007501000125015001750200022502500275030003250350037504000
1/cm
-15
0
15
30
45
60
75
90
105
120
%T
3801.82
3323.46
2590.49
2499.83
2436.18
2314.66
2247.15
2169.99
2011.82
1915.38
1799.65
1728.28
1595.18
1242.20
1147.68
1091.75
1041.60
923.93
812.06
750.33
665.46
630.74
572.88
547.80
497.65
sample A

21. FTIR spectra of placebo formulation
21

22. IN-VITRO DISSOLUTION STUDIES
Apparatus : USP XXIV dissolution tester
Type : Paddle
RPM : 50 rpm
Temperature : 37 ± 5°C
Dissolution mediums : pH 1.2 buffer solution
Dissolution fluid volume : 900 ml
Time of sample withdrawn : 1h, 2h, 4h, 6h, 8h, 10h,12h.
Volume of sample withdrawn : 5 ml
Volume of sample replaced : 5ml
UV estimation λmax value : 226 nm
22

23. PERCENT GLICLAZIDE RELEASED FROM TABLETS WITH HPMC & CBP RATIO IS
(0:6, 5:1, 4:2, 3:3.)
Time (Hour) Percent Gliclazide released
HC06 HC51 HC42 HC33
1.00 97.92 ± 1.27 12.07 ± 1.78 17.4 ± 4.42 24.24 ± 0.10
2.00 ----- 18.19 ± 1.47 26.11 ± 1.98 39.31 ± 0.45
4.00 ----- 22.78 ± 0.76 37.72 ± 0.15 59.88 ± 2.03
6.00 ----- 29.95 ± 1.05 46.22 ± 3.51 83.88 ± 1.52
8.00 ----- 40.32 ± 1.06 63.84 ± 3.81 97.08 ± 1.52
10.00 ----- 54.26 ± 1.04 81.6± 5.60 -----
12.00 ----- 68.64 ± 1.78 97.92 ± 8.90 -----

24. PERCENT GLICLAZIDE RELEASED FROM TABLETS WITH A HPMC & GG RATIO
IS (0:6, 5:1, 4:2, 3:3.)
Time (Hour) Percent Gliclazide released
HG06 HG51 HG42 HG33
1.00 22.83±1.93 10.15±0.45 13.56±0.76 16.48±0.76
2.00 36.98±0.20 16.03±1.12 18.76±0.45 23.66±2.61
4.00 56.46±2.44 20.32±2.03 26.88±0.76 37.7±1.35
6.00 99.12±3.81 26.76±1.62 39.07±0.81 51.21±2.29
8.00 ----- 38.61±3.25 52.46±0.76 63.36±3.30
10.00 ----- 48.76±1.01 69.96±1.78 79.92±1.78
12.00 ----- 62.76±1.78 83.76±3.05 98.64±2.50

25. 25
In vitro buoyancy study of optimized batch formulation HG33

26. Formulation
Zero
order
First
order
Higuchi
order
Korsmeyer and Peppas equation
R2 R2 R2 R2 n Release Mechanism
HG51 0.9740 0.9273 0.9730 0.9297 0.765 Anomalous (non fickian)
HG42 0.9875 0.9050 0.9050 0.9716 0.851 Anomalous (non fickian)
HG33 0.9957 0.7193 0.9607 0.9905 0.781 Anomalous (non fickian)
HC51 0.9881 0.9159 0.9949 0.9949 0.665 Anomalous (non fickian)
HC42 0.9888 0.7566 0.9440 0.9638 0.735 Anomalous (non fickian)
HC33 0.9690 0.9080 0.9040 0.9227 0.740 Anomalous (non fickian)
RELEASE KINETICS DATA FROM GLICLAZIDE
GASTRORETENTIVE FLOATING TABLETS

27. By fitting the release data into the Korsmeyer-Peppas
equation,
The values of n for all tablet formulations was
ranged from 0.665 to 0.851, indicating drug release could have
occurred by a combination of several processes like diffusion,
swelling of polymer HPMC (relaxation) and erosion. High
values of correlation coefficient ranging from 0.9040 to 0.9957
indicate goodness of fitness of dissolution data to the power
law equation for HPMC,CBP and GG based tablets.
DRUG RELEASE MECHANISM

28. Formulation
Code
Thickness*
(mm± SD)
Hardness*
(Kg/cm2± SD)
Friability
(%)
Drug Content*
(% ± SD)
Weight
Variation
( %)
HG33 3.45 ± 0.18 4.36 ± 0.13 0.757 97.06 ± 3.02 4.64
HC42 3.32 ± 0.20 4.48 ± 0.09 0.621 98.11 ± 2.66 1.68
*Data obtained were average of 05 determinations
Stability data of optimized batch formulation HG33 & HC42 after
storage at 40oC / 75% RH for 30 Days
Conclusion
 No change in physical appearance, physical properties drug content
and dissolution studies was observed.
 This insignificant change indicates that the developed formulation
could provide a better shelf life.

29. Release data of optimized batch HG33 after storage period of 30
Days at 40oC / 75% RH
Time
(H)
Percent Gliclazide released
Before storage After storage
1 16.48 ± 0.76 14.04 ± 0.27
2 23.66 ± 2.61 21.91 ± 0.33
4 37.7 ± 1.35 34.75 ± 0.31
6 51.21 ± 2.91 48.86 ± 0.62
8 63.36 ± 3.3 59.4 ± 1.42
10 79.92 ± 1.78 76.56 ± 0.57
12 98.64 ± 2.5 95.52 ± 1.35
0
20
40
60
80
100
0 2 4 6 8 10 12
percentGliclazidereleased%
Time in Hour
HG33 Before storage
HG33 After storage

30. FTIR spectra of optimized batch HG33 tablet formulation after storage
5007501000125015001750200022502500275030003250350037504000
1/cm
-15
0
15
30
45
60
75
90
105
120
%T
3296.46
3296.46
2590.49
2501.76
2436.18
2312.73
2247.15
2169.99
2011.82
1915.38
1799.65
1710.92
1595.18
1242.20
1157.33
1087.89
1041.60
995.30
925.86
812.06
752.26
659.68
468.72
sample B

31. CONCLUSION
From the data of …….
Buoyancy lag time (30 & 43 sec),
Floating time (12h) &
In vitro dissolution studies ( > 96 % ),
It was concluded that formulation HG33
(HPMC:GG,3:3) & HC42 (HPMC:CBP,4:2) found to be suitable
for designing floating drug delivery system.
Further, the optimized formulations HG33 and HC42 stored
for a period of 30 days shows no change in physical properties,
drug content and in vitro release pattern indicating developed
formulation could provide a better shelf life.

32. Thank
You