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FORMULATION AND EVALUATION OF BILAYERED FLOATING TABLETS OF

METFORMIN HYDROCHLORIDE

Article · February 2012

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 R.Margret Chandira et al. IRJP 2012, 3 (2)

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY

www.irjponline.com ISSN 2230 – 8407
Research Article

FORMULATION AND EVALUATION OF BILAYERED FLOATING TABLETS OF

METFORMIN HYDROCHLORIDE
R.Margret Chandira*, P.Palanisamy, B.Jayakar
Vinayaka Mission’s College of Pharmacy, Vinayaka Missions University, Salem, Tamil Nadu, India
Article Received on: 12/11/11 Revised on: 30/12/11 Approved for publication: 18/01/12

*Email: [email protected]
ABSTRACT
Diabetes is a chronic metabolic disease characterized by high glucose levels in the blood. Sustained release gastro retentive dosage forms enable prolonged
and continuous input of the drug to the upper parts of gastrointestinal tract and improve the bioavailability of medication that is characterized by narrow
absorption window. Gastro retentive floating drug delivery systems (GFDDS) of Metformin HCl, an antidiabetic drug with an oral bioavailbility of only 50%
(because of its poor absorption from lower gastrointestinal tract) have been designed to increase its residence time in the stomach without contact with the
mucosa was achieved through the preparation of floating bilayer matrix tablet by direct compression technique, by using HPMC as release retardant, and
NaHCO3 as gas generating agent to reduce floating lag time. Bilayer Floating tablets were evaluated for Hardness, Friability, Weight Variation, Drug content,
Floating properties and In-vitro release pattern. The In-vitro drug release followed Zero order Kinetics and drug release was found to be diffusion controlled.
Key Words : Metformin Hcl, Bi-layer floating tablets.

INTRODUCTION bicarbonate, Magnesium stearate was gifted by ABC

Floating Drug Delivery Systems (FDDS) have a bulk density Laboratory (Chennai, India).
lower than gastric fluids and thus remain buoyant in the FORMULATION DESIGN
stomach for a prolonged period of time, without affecting the Preparation Of Bilayer Floating Release Matrix Tablets
gastric emptying rate. While the system is floating on the With Immediate Release Layer
gastric contents, the drug is released slowly at a desired rate Preparation Of Immediate Release Layer
from the system. After the release of the drug, the residual Controlled release formulations take some time to achieve
system is emptied from the stomach. This results in an effective plasma levels. Therefore an immediate release layer
increase in the GRT and a better control of fluctuations in the is formulated along with controlled release layer to give an
plasma drug concentrations. Floating systems can be initial plasma level, which is then maintained by controlled
classified into two distinct categories, non-effervescent and release layer.
effervescent system. Drug loading granules (as an immediate release dose) were
prepared by mixing metformin hydrochloride with sodium
starch glycolate and PVP-K-30 and micro crystalline
cellulose granules and mixed with magnesium stearate and
iron oxide red by direct compression technique.
The composition is shown in Table 1
Preparation Of Matrix Layer For Controlled Release
The matrix layer contains uniform mixture of drug, polymer
and excipients including gas-generating agent. The tablets
were prepared by using direct compression technique.
Weighed quantities of drug equivalent to 375 mg metformin
Fig 1: Graphic Of Buoyant Tablet, Which Is Less Dense Than The hcl, was mixed properly in a mortar with weighed amount of
Stomach Fluid Therefore It Remains In The Fundus.
polymer and excipients as shown in Table 2. The well-mixed
powder was compressed using a ELITE multi station
Aim And Objective punching machine. The hardness is adjusted for the required
The present study undertaken with the following objectives: amount.
To design the controlled release oral bilayer floating tablet to Preparation Of Bi-Layer Tablets
increase the resident time of the drug in the stomach and Bi-layer tablets were prepared by combining batch
release for extended period of time in order to:- FD/MTH/D of immediate release layer with various
Ø Increase the bioavailability of drug formulations of controlled release layer. Batch FD/MTH/D
Ø Decrease the dosing frequency showed disintegration time of 1.45 min was selected for
Ø Improve patient compliance. further studies. Matrix tablet is prepared as mentioned above
MATERIALS AND METHODS in the procedure of preparation of matrix layer controlled
Metformin hydrochloride was procured by Micro Labs release. After the compression upper punch was lifted and the
(Bangalore, India); HPMC K 100M, HPMC K 4M was gifted
blend of powder for immediate release layer was poured in
by Colorcon Asia pvt LTD(India); Sodium starch glycolate, the die, containing initially compressed matrix tablet and
PVP K 30, Micro-crystaline cellulose was gifted by Nice compression was controlled to produce a 4 to 6 kg crushing
Chemicals Laboratory (India); Iron Oxide-Red, Sodium strength. These tablets are evaluated for Thickness, hardness,

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 R.Margret Chandira et al. IRJP 2012, 3 (2)

friability and Dissolution Profile. The composition is shown Buoyancy Determination

in Table No.3 The time taken for dosage form to emerge on surface of
Compression of Bi-layer Tablets madium is called floating lag time, duration of time by which
A tablet bi-layer press is simply a tablet press that has been the dosage form constantly emerges on surface of medium is
modified so that it has 2 die filling and compression cycles called Total floating time (TFT).
for each revolution of the press. In short, each punch One tablet from each formulation batch was placed in USP
compress twice, once for the first layer of a two layer tablet type II dissolution apparatus containing 900 ml 0.1 N HCl
and a second time for the second layer. If the first layer is dissolution medium using paddle at a rotational speed of 75
compressed so hard that the second layer will not bond it, or rpm. The temperature of medium was maintained at 37° ±
will bond so poorly that upon ejection the layers are easily 2°c. The time taken for tablet to emerge on surface of
separated for weighing. Once the proper weight adjustment medium and the duration of time by which the tablet
have been made by adjusting the die fill, the pressure is constanly remain on surface of medium was noted.
adjusted to the proper tablet hardness and bonding of the The Results are shown in Table 11.
layers. In this two layer tablet press, two hoppers above the Swelling Study
rotary die table feed, granulated material to two separate feed The individual tablets were weighed accurately and kept in
frames without intermixing continuous, gentle circulation of 50ml of water. Tablets were taken out carefully after 60min,
the materials. Through the hoppers and feed frames assures blotted with filter paper to remove the water present on the
uniform filling without segregation of particle sizes that surface and weighed accurately. Percentage swelling was
would otherwise carry over to the second layer and affect calculated by using formula;
layer weight, tablet hardness, so use colored granulation Swelling study = wet weight – dry weight/ dry weight ´ 100
taken for one layer. The Results are shown in Table No.12.
Post - compression parameters In-Vitro Drug Release Study
Evaluation of bilayer tablet Dissolution of the tablet of each batch was carried out using
Thickness of Tablets USP type II apparatus using paddle. 900 ml of dissolution
Thickness and diameter were measured using a calibrated media was filled in a dissolution vessel and the temperature
dial caliper. Three tablets of the formulation were picked of the medium were set at 37° ± 2°c. one tablet was placed in
randomly and thickness was measured individually. The each dissolution vessel and the rotational speed of paddle was
Results are shown in Table 7 set at 50 rpm.The 10 ml of sample was withdrawn at
Hardness of Tablets predetermined time interval for 12 hours and same volume of
Hardness was measured using monsanto hardness tester. For fresh medium was replaced. The samples were analyzed for
each batch three tablets were tested. The Results are shown in drug content against dissolution media as a blank at 233 nm
Table No.7 using double beam UV visible spectrophotometer.
Friability Details of dissolution test
Twenty tablets were weighed and placed in the roche Apparatus : DA USP XXIII
friabilator and apparatus was rotated at 25 rpm for 4 minutes. Speed : 50 rpm
After revolutions the tablets were dedusted and weighed Volume of medium : 900 ml
again. The percentage friability was measured using the Stirrer : Paddle type
formula, Aliquot taken at each time interval : 10 ml
% F = {1-(Wt/W)} x 100 Medium used : 0.1 N Hcl (pH 1.2)
Where, % F = Friability in percentage Temperature : 37±0.5
W = Initial weight of tablet The Results are shown in Table 13-15.
Wt = Weight of tablets after revolution RESULTS AND DISCUSSION
The Results are shown in Table 7 Evaluation Of Bilayered Floating Tablet
Weight Variation Pre-Compression Parameters
Twenty tablets were randomly selected from each batch and The excipients used in the formulation such as metformin
individually weighed. The average weight and standard HCl, HPMC, Sodium starch glycolate, Sodium bicarbonate,
deviation of 20 tablets was calculated. The batch passes the PVP-K-30,Micro crystalline cellulose were evaluated for
test for weight variation test if not more than two of the Angle of repose, Bulk density, Tapped density,
individual tablet weight deviate from the average weight by Compressibility index, Hausner ratio as per the procedure
more than the percentage shown in and none deviate by more described under methodology section (6.5).
than twice the percentage shown. The data’s are shown in Table 7.
The Results are shown in Table 4. Post Compression Parameters
Drug content Thickness Of Tablets
The assay of the drug content was carried by weighing ten Thickness of tablets was measured by vernier calipers using
tablets and calculated the average weight. Then the tablets the procedure described in methodology section(6.7.1). The
were triturated to get a fine powder. From the resulting diameter of all the formulations were found within the
weighed accurately about 155 mg of the powder (equivalent acceptable range i.e. ± 5% of the respective average weight.
to 100 mg) of metformin HCl was taken, shake with 70 ml of The results are shown in Table 8.
water for 15 minutes, dilute to 100 ml with water and filter. Hardness Of Tablets
Dilute 10 ml of the filterate to 100 ml with water. Further The hardness of all the formulations were checked by using
dilute 10 ml to 100 ml with water and measure the Monsanto Hardness tester, by the method described in
absorbance at the maximum at about 233 nm. The Results are methodology section(6.7.2). The average hardness of
shown in Table 10.
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 R.Margret Chandira et al. IRJP 2012, 3 (2)

bilayered tablet formulations in the range of 5-7kg/cm2. The polymer used was greater, which was supported by Li and
results are shown in Table 8. Co-workers et al. who reported that higher viscosity grade
Fraibility Of Tablets generally exhibited greater floating capability.
The friability of all the formulations was checked using roche Swelling Study
friabilator according to the method in methodology Swelling study was performed on all batches (FD/MTH/D+G
section(6.7.3). The average friability for all the formulations to FD/MTH/D+J) for 5 hrs. The results of swelling index
comes in the range of 0.320-0.650% . The results are shown were shown in Table No.10 and swelling index against time
in the Table 8. (hrs) was plotted in Fig.3. From the results it was concluded
Weight Variation Test that swelling increases as the time passes because the
Uniformity of weight test for all the formulations were polymer gradually absorb water due to hydrophilicity of
carried out using the procedure described in the methodology polymer. The outermost hydrophilic polymer hydrates and
section (6.7.4). Results of uniformity of weight are shown in swells and a gel barrier are formed at the outer surface. As
the Table No.10. All the formulations were came under the the gelatinous layer progressively dissolves and/or is
acceptable limit of ±5%. dispersed, the hydration swelling release process is
Disintegration Time Test continuous towards new exposed surfaces, thus maintaining
In the formulation of bilayered floating tablets, the purpose of the integrity of the dosage form. The viscosity of the
immediate release layer is to quick release of drug. Therefore polymer had major influence on swelling process, matrix
this layer should disintegrate immediately for drug to be integrity, as well as floating capability, hence from the results
readily available for dissolution and absorption. it can be studied that linear relationship exists between
Disintegration time mainly depends upon the concentration of swelling process and viscosity of polymer.
disintegrant, SSG is used as a disintegrant. The disintegration In-vitro Drug Release Studies
time was found to be 3.23-1.45 min. The disintegration times In-vitro drug release studies were performed as per the
are shown in the Table No.9. and the rate of disintegration procedure described in methodology section. (6.7.8). The
was found to be in the following order. percentage cumulative drug release was plotted against time
FD/MTH/D ˃ FD/MTH/C ˃ FD/MTH/B ˃ FD/MTH/A to obtain drug release profiles. The results are shown in
Drug Content Uniformity respective Table 14-16 and Figure 4. It is clear from the
The content uniformity of tablets was determined as per the Tables 14-16 and Fig 3-6. That the formulations show
procedure described under methodology section. (6.7.5).All biphasic release of metformin HCl. In the first phase the
the formulations passes the content uniformity tests as per the loading dose (immediate release) was released in less than 30
BP specifications. min, because of prompt disintegration of the fast releasing
The results are shown in the Table 11. layer and the enhanced rate of dissolution of metformin HCl
Buoyancy Determination from the system. This behavior was identified for all
In this evaluation study, Floating lag time (FLT) and the formulations (sustained part) after the release of first part
Total floating time (TFT) of the tablet was determined. The (loading drug).Two different batches were formulated
floating time of the tablet was determined as per the individually with HPMC K 4 M and HPMC K 100 M. when
procedure mentioned in the methodology section.(6.7.6). The these polymers are formulated alone, the release rate was not
results are shown in the Table 9. that much retarded with in the fisrt hour. The release rate was
Results of floating properties study reveals that all tablets had found to be 12.85 and 16.0 % respectively. As we discussed
good floating properties. This might be due to the presence of earlier the other batches were formulated with mixture of two
gas generating agent i.e., NaHCO3, content. These finding polymers. Four different batches were formulated for
were supported by study of Baumgartner et al. Who reported bilayered tablets of Metformin HCl, the first batches
that incorporation of sodium bicarbonate helps to improve formulated with the polymer to polymer ratio of
floating properties by reacting with gastric fluid when dosage 1:1(FD/MTH/G). It showed the cumulative % release of
form comes in contact and produce carbon dioxide gas which 93.36% at 10 hrs. The remaining three batches were
entrapped inside the hydrophilic matrices leads to increase in formulated with the polymer to polymer ratio’s of 1:2
volume of dosage form resulting in lowering of density and (FD/MTH/H), and 1:3 (FD/MTH/I), and 1:4 (FD/MTH/J)
dosage form starts to float. From the results of floating lag respectively, which showed a cumulative % release of 95.23,
time it was concluded that as the concentration of gas 97.11, 98.97 % of Metformin HCl. The release rate was not
generating agent increases the floating lag time get shortens. that much affected in all the formulations i.e.,
These findings were supported by study of park et al. who (FD/MTH/D+G, H, J and I). But the increasing concentration
reported that as the concentration of gas generating agent of polymer to polymer ratio will increase the drug release to a
(NaHCO3) was increased the floating lag time get shortened maximum level. As our main aim was on the floatability the
and at the same time floating ability get increased. Another dosage form in stomach, the batch FD/MTH/D+J showed a
aspect of result of these studies clears that the level as well as minimum lag time and maximum floating time with
viscosity of the polymer had a great impact over the floating maximum % release, it was considered as a successful batch
lag time and total floating time, as the level and viscosity of from our formulations .
the polymer was reduced greater when the viscosity of the

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 R.Margret Chandira et al. IRJP 2012, 3 (2)

Table 1: Formulation of Immediate Release

FORMULATIONS
CONTENT
FD/MTH/A FD/MTH/B FD/MTH/C FD/MTH/D
Metformin HCL 125 125 125 125
Sodium Starch Glycolate 4 8 12 16
PVP-K-30 5 5 5 5
Iron Oxide red 2 2 2 2
Micro crystalline cellulose 35 31 27 23

Magnesium stearate 4 4 4 4

All the Ingredients are taken in mg.

Total wt. of IR layer-175 mg

Table 2: Formulation of Floating layer (SR)

FORMULATIONS
CONTENT
FD/MTH/E FD/MTH/F FD/MTH/G FD/MTH/H FD/MTH/I FD/MTH/J

Drug 375 375 375 375 375 375

HPMC
--- 57.5 32.5 27.5 23.75 21.5
K4M
HPMC
57.5 --- 32.5 55.0 71.25 86.0
K 100 M
NaHCO3 46.0 46.0 46.0 46.0 46.0 46.0

Citric acid 11.5 11.5 11.5 11.5 11.5 11.5

PVP-k-30 23.0 23.0 23.0 23.0 23.0 23.0

MCC 56.25 56.25 48.75 31.25 18.75 6.25

Mag.
5.75 5.75 5.75 5.75 5.75 5.75
Stearate
All the Ingredients are taken in mg.
Total wt. of SR layer-575 mg

Table 3: Formulation of bilayered tablet

FORMULATIONS
CONTENT
FD/MTH/D+G FD/MTH/D+H FD/MTH/D+I FD/MTH/D+J
Loading Drug 175 175 175 175
Metformin HCl 375 375 375 375
HPMC K4 M 32.5 27.5 23.75 21.5

HPMC K100 M 32.5 55.0 71.25 86.0

NaHCO3 46.0 46.0 46.0 46.0

Citric acid 11.5 11.5 11.5 11.5

PVP-K-30 23.0 23.0 23.0 23.0

MCC 48.75 31.25 18.75 6.25

Mag.Stearate 5.75 5.75 5.75 5.75
All the Ingredients are taken in mg.
Total wt. of Bi-layer-750 mg

Table 4: Weight Variation Tolerances for Uncoated Tablets

S. No. Average weight of Tablets (mg) Maximum percentage difference allowed
1. 130 or Less 10
2. 130 to 324 7.5
3. More than 324 5.0

Table 5
Time (Hours) Percentage of drug release
1-3 10-25
9 45-85
12 Not Less Than 75

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 R.Margret Chandira et al. IRJP 2012, 3 (2)

Table 6 : Pre-compression parameters of Drug and Excipients

Angle of repose Bulk density Tapped density Compressibility index Hausner's ratio
Parameters
(°) (gm/cc) (gm/cc) (%)

Metformin Hcl 38.24 0.524 0.614 14.68 1.17

HPMC K100 M 26.72 0.298 0.477 37.17 1.58

HPMC K 4 M 25.25 0.304 0.481 36.45 1.57

SSG 26.42 0.468 0.670 29.88 1.42

PVP-K-30 23.32 0.590 0.702 15.69 1.17

NaHCO3 25.17 0.334 0.423 20.80 1.25

MCC 22.14 0.512 0.691 25.41 1.33

Table 7 : Results of Evaluation of Thickness, Hardness and Friability of Bilayered Floating Formulations.
Formulation Thickness in Hardness Friability
Code mm ± S.D. Kg/cm2 ± S.D. % ± S.D

FD/MTH/D+G 5.13±0.11 6.23±0.05 0.322±0.1

FD/MTH/D+H 5.06±0.11 6.33±0.15 0.771±0.13

FD/MTH/D+I 5.40±0.2 6.16±0.05 0.833±0.11

FD/MTH/D+J 5.33±0.23 6.63±0.05 0.642±0.14

Table 8 : Disintegration time of different immediate release formulations

Formulation Code Disintegration Time (min)

FD/MTH/A 3.23

FD/MTH/B 2.53

FD/MTH/C 2.16

FD/MTH/D 1.45

Table 9 : Results of Evaluation for Weight Variation of Bilayered floating formulations

Formulation Code % Weight Variation Range

FD/MTH/D+G 0.762±0.019

FD/MTH/D+H 0.769±0.019

FD/MTH/D+I 0.770±0.015

FD/MTH/D+J 0.769±0.017

Table 10 : Results of Evaluation of Drug content of Bilayered floating formulations

Formulation Code Amount of Metformin HCl (mg) Drug Content (%)

FD/MTH/D+G 494.50 98.90

FD/MTH/D+H 497.28 99.45

FD/MTH/D+I 495.72 99.14

FD/MTH/D+J 498.85 99.80

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 R.Margret Chandira et al. IRJP 2012, 3 (2)

Table 11: Evaluation of Floating Lag Time and Total Floating Time

Formulation Code Floating Lag Time (min) Total Floating Time (hrs)

FD/MTH/D+G 4.15 7.35

FD/MTH/D+H 3.40 8.10

FD/MTH/D+I 2.45 10.30

FD/MTH/D+J 1.45 12.17

Table 12: Percentage Swelling Of Bilayered Floating Formulations

PERCENTAGE SWELLING

Time (hrs) FD/MTH/D+G FD/MTH/D+H FD/MTH/D+I FD/MTH/D+J

1 20.13 25.52 29.72 31.52

2 27.11 33.33 38.51 44.23

3 36.24 39.68 54.32 64.63

4 45.23 50.13 67.02 79.60

5 55.97 61.50 73.51 88.47

Table 13: Invitro Drug Release Profile Of Immediate Release Layer

Cumulative Drug Release (%)
TIME (min)
FD/MTH/A FD/MTH/B FD/MTH/C FD/MTH/D
5 23.60 38.55 44.06 59.80

10 37.00 52.76 62.21 76.39

20 50.42 69.34 75.65 85.91

30 68.57 82.79 85.18 100.17
40 78.10 93.12 99.44 97.92

50 90.76 100.30 97.19 96.44

60 99.53 97.19 95.72 94.09

Table 14: Invitro Drug Release Profile Of Floating Layer (Sustained Release Layer) Formulations
Cumulative Drug Release (%)

Time
FD/MTH/E FD/MTH/F FD/MTH/G FD/MTH/H FD/MTH/I FD/MTH/J
(hrs)

1 12.85 16.0 7.34 8.91 9.70 10.22

2 20.21 21.52 23.36 25.72 30.18 35.17

3 27.57 29.94 28.37 33.36 37.30 41.50

4 36.52 40.20 36.79 44.41 48.88 52.04

5 40.49 52.05 49.69 52.33 57.85 62.07

6 48.15 64.43 61.02 64.71 69.72 72.10

7 54.76 76.05 72.10 76.59 82.39 84.51

8 65.05 81.64 82.94 86.38 89.24 90.90

9 74.82 85.66 87.22 90.67 91.50 94.41

10 85.92 88.12 93.36 95.23 97.11 98.97

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 R.Margret Chandira et al. IRJP 2012, 3 (2)

Table 15 : Invitro Drug Release Profile Of Bilayered Floating Formulations

Cumulative Drug Release (%)

Time(hrs) FD/MTH/D+G FD/MTH/D+H FD/MTH/D+I FD/MTH/D+J

1 31.27 32.85 34.42 36.0

2 36.8 39.16 41.15 42.12

3 45.11 46.89 48.66 49.46

4 49.49 53.03 54.82 55.79

5 58.01 59.59 60.98 62.15

6 67.31 69.88 71.07 72.27

7 74.87 76.25 78.03 79.42

8 83.02 84.6 85.4 86.78

9 88.42 90.4 92.18 94.56

10 94.62 95.16 97.41 98.59

Table 16: Regression coefficient values obtained from the plots of bilayer floating formulations (FD/MTH/D+G, H, I and J)
Hixon-crowel
Zero order eqn. First order eqn. Higuchi eqn. Peppas eqn.
eqn.
Formulation
Code Regression Regression Regression Regression Regression Possible release
Coefficient Coefficient Coefficient Coefficient Coefficient kinetic models
(r) (r) (r) (r) (r)

FD/MTH/D+G 0.954 0.903 0.970 0.959 0.959 Zero order

FD/MTH/D+H 0.944 0.909 0.976 0.966 0.963 Zero order

FD/MTH/D+I 0.939 0.858 0.975 0.965 0.943 Zero order

FD/MTH/D+J 0.936 0.822 0.972 0.958 0.929 Zero order

Fig 2

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 R.Margret Chandira et al. IRJP 2012, 3 (2)

Fig 3

Fig 4

Fig 5: Plot’s of Swelling Index

Figure 6: Invitro Drug Release Plot’s Of Immediate Release Layer

Fig 7 & 8: Invitro Drug Release Plot’s Of Floating Layer (Sustained Release Layer) Formulations

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 R.Margret Chandira et al. IRJP 2012, 3 (2)

Fig 9: Invitro Drug Release Plot’s Of Bilayered Floating Formulations

The immediate release layer was formed by using SSG as a machine. Prepared tablets were subject to various evaluation
Disintegrant that was widely used due to its effectives in parameters such as Thickness, Hardness, Weight variation,
standard concentration range of 2-8%. SSG gives the Friability, Disintegration, Buoyancy study and In-vitro drug
maximum disintegration at the 8%. In the prepared release study, Kinetic Parameters, and Accelerated stability
formulations FD/MTH/D had given less disintegration time studies as per ICH guidelines. From FTIR Spectral analysis,
as compared to the remaining formulation. In these it was concluded that there was no interference in the
formulations FD/MTH/D gives the best result as compared to functional group as the principle peaks of the drug were
FD/MTH/A, FD/MTH/B, and FD/MTH/C. Bilayered tablets found to be unaltered in the drug polymer physical mixture.
were formulated as per formulation design, in that sustained Thus, conclusion can be made that stable floating dosage
layer was considered to have an important effect on the form can be developed for metformin Hcl for the controlled
release from the HPMC matrices. Different grades of HPMC release by bilayered floating tablets. It was observed that
(K 100 M and K 4 M) were used as a polymer. HPMC K 100 tablet of batch FD/MTH/D+J given maximum drug release
M was chosen because it is widely used as low density and good floatability.
hydrocolloid system, upon contact with water a hydrogel CONCLUSION
layer would be formed, it act as a gel boundary for the From the above experimental results it can be concluded that,
delivery system. But it would fail to retard the release of drug Sodium bicarbonate has predominant effect on the buoyancy
through the matrix and the tablet integrity problems also. lag time, while HPMC K 100 M and HPMC K4 M has
HPMC K 100 M were reported to have a duration of predominant effect on total floating time and drug release.
buoyancy of more than 8hrs. in the simulated meal media as Bilayered floating matrix tablet with immediate release layer
well as in the distilled water. HPMC K 4 M was used in the give good floating and a controlled release pattern after initial
combination with HPMC K 100 M to slow the drug release at immediate release. In-vitro release rate studies showed that
the initial type of drug release (sustained part) and K 4 M the maximum drug release was carried out in the
rectified integrity problems and retard the release. To FD/MTH/D+G, FD/MTH/D+H, FD/MTH/D+I, and
overcome an initial burst effect, the high viscosity HPMC FD/MTH/D+J in the required period of time. But
polymer used. HPMC K 4 M gives prolonged floating and FD/MTH/D+J showed a minimum lag time and maximum
drug release as compare to the low viscosity polymers. Our floating time with maximum % drug release (98.59%) and
main focus was on the floatability of the dosage form in the considered as a successful batch. When the release data was
stomach, so the HPMC concentration was increased toward analyzed as per Zero and First order kinetic models,
the experimental design. indicating that the drug release from all the batches followed
When the release data was analyzed as per Zero and First Zero order kinetics, and the prepared formulations followed
order kinetic models, the best fit with high correlation Higuchi profile.When the release data was analyzed as per
(r˃0.936) was observed with Zero order model indicating that peppas equation, the release exponent n was found in the
the drug release from all the batches followed Zero order range of 0.46 to 0.50 indicating non-fickian (anomalous)
kinetics, and the prepared formulations followed Higuchi diffusion controlled as the release mechanism from all the
profile. prepared tablets. The stability study revealed that there was
When the release data was analyzed as per peppas equation, no significant change in dissolution profile for a period of 1
the release exponent n was found in the range of 0.46 to 0.50 month of the selected formulation (FD/MTH/D+J) found to
indicating non-fickian (anomalous) diffusion controlled as be stable over the storage period and conditions tested as per
the release mechanism from all the prepared tablets. ICH Guidelines. From the study it is evident that a promising
SUMMARY controlled release by bilayered floating tablets of metformin
Hence in present investigation, For the formulation of Hcl can be developed. Further detailed investigations are
floating tablets HPMC (K 100 M and K 4 M) used as a required to establish efficacy of these formulations. Further
matrix forming agent. Other excipients used are sodium In-vivo investigations are required to correlate In-vitro
starch glycolate (disintegrate), sodium bicarbonate (as a gas release studies. Further preclinical and clinical study is
generating agent), PVP-K-30 (Binder), microcrystalline necessary for use of Metformin Hcl bilayered floating tablets
cellulose (Diluent) and Magnesium stearate as a lubricant. as oral controlled drug delivery system.
The drug and polymers are subjected to various ACKNOWLEDGMENT
preformulation studies such as Angle of repose, Bulk density, Authors are thankful to Prof.(Dr.) B.Jayakar, principal
Tapped density, Compressibility Index, Hausner ratio. Vinayaka missions college of pharmacy, Salem,Tamilnadu
characterization using FTIR spectral analysis, Drug and and providing all the facilities for this research Project.
excipients compatibility studies. The tablets were
compressed using multi station rotary bilayer punching
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 R.Margret Chandira et al. IRJP 2012, 3 (2)

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Source of support: Nil, Conflict of interest: None Declared

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