FORMULATION DEVELOPMENT OF METFORMIN HYDROCHLORIDE AND PIOGLITAZONE BILAYERED TABLETS USING NATURAL GUMS

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Ananda Kumar Chettupalli World Journal of Pharmaceutical Research
FORMULATION DEVELOPMENT OF METFORMIN
HYDROCHLORIDE AND PIOGLITAZONE BILAYERED
TABLETS USING NATURAL GUMS
*Ananda Kumar Chettupalli
Department of Pharmaceutics, Ph.D Scholar, JJT.University, Rajasthan, India.
ABSTRACT
Hyperglycemia is the technical term for high blood glucose (sugar). It
happens when the body has too little or not enough insulin or when the
body can‘t use insulin properly. The main objective of the present
research work was to develop a bilayer tablet of immediate release
Pioglitazone and controlled release Metformin Hydrochloride, which is
used as an Anti-hyperglycemic agent. Metformin Hydrochloride has
biological half-life nearly about 6 hours, so, an attempt was made in
the direction of preparation and optimization of a combination of
sustained release and immediate release in a single tablet. In controlled
release layer natural gums like xanthum gum, gum trgacanth and guar
gum were used as retarding materials and in immediate release laye
croscarmellose sodium was used as a superdisintegrent to give the faster release of
pioglitazone. The tablets were prepared by wet granulation method and by direct
compression. Granules were evaluated for precompression parameters and the tablets were
evaluated for post compression parameters.
Key Words: Bilayer tablets, Metformin Hydrochloride, pioglitazone, xanthum gum, guar
gum, gum tragacanth and crosscarmellose sodium.
INTRODUCTION1
Oral route is one of the most popular routes of drug delivery due to its ease of administration,
patient compliance, least sterility constraints and flexible design of dosage form.
Ideally a drug to provide desired therapeutic action should arrive rapidly at the site of action
in optimum concentration, remain there for the desire time, be excluded from other site. The
fact that absorption rate of drug into the body can be decreased by reduction of the rate of
World Journal of Pharmaceutical research
Volume 3, Issue 1, 1435-1449. Research Article ISSN 2277 – 7105
Article Received on
20 October2013
Revised on 24 November
2013,
Accepted on 30 December
2013
*Correspondence for
Author:
Ananda Kumar Chettupalli
Department of Pharmaceutics,
Ph.D Scholar, JJT.University,
Rajasthan, India.
anand33.chettupalli@gmail.com

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release of the drug from the dosage form is one of the most recent and interesting result of
pharmaceutical research. Once a day or at the most twice a day formulation is of most
precious sorts for scientists working with oral dosage forms. A sustained release preparation
that makes once or twice daily administration of drug possible might be an advantageous
dosage form, especially in long-term therapy. This ideal dosing regimen, which enhances
patient compliance and helps guard against overdosing and side effects, is made possible by
controlled release delivery systems, which use a variety of mechanisms to deliver and
maintain the drug at a certain level in the patient’s blood stream.
Over 90% of the formulations manufactured today are ingested orally. This shows that this
class of formulation is the most popular worldwide and the major attention of the researcher
is towards this direction. With advancement in technology and increase in awareness, towards
modification in standard tablet is done to achieve better acceptability as well as
bioavailability because of which newer and more efficient tablet dosage forms are being
developed. The main reasons behind formulation of different types of tablets are to create a
delivery system that is relatively simple and inexpensive to manufacture, provide the dosage
form that is convenient from patient‘s perspective and utilize an approach that is unlikely to
add complexity during regulatory approval process
Dual release tablet is a unit compressed tablet dosage form intended for oral application. It
contains two layers in which one layer having conventional or immediate release part of
single or multiple actives; another layer is controlled release part of single or multiple
actives‖. They are also called as bilayer tablet, multi-layer matrix tablet. 2
For many disease states the ideal dosage regimen is that by which an acceptable therapeutic
concentration of drug at the site (s) of action is attainted immediately and is then maintained
constant for the desired duration of the treatment3
. Over the past 30 years as the expense and
complication involved in marketing new drug entities have increased, with concomitant
recognition of the therapeutic advantage of modified release per oral dosage forms, greater
attention has been focused on development of sustained, controlled release and delayed
release system. There are several reasons for the attractiveness of this dosage form. It is
generally recognized that for many disease states, a substantial number of therapeutically
effective compounds already exist. The effectiveness of these drugs however is often limited
by side effects or the necessity to administer the compound in a clinical setting.

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MATERIALS AND METHODS
MATERIALS
Pioglitazone hydrochloride and Metformin was obtained as a gift sample from Granules India
ltd. Crosscarmellose sodium, Pvpk30, Xanthum gum, Guar gum, Gum tragacanth, Micro
crystalline cellulose, Lactose, Magnesium stearate, Talc and Sunset yellow were obtained
from Yarrow Chem. Products, Mumbai. All the ingredients used were of analytical grade.
METHODS
Formulation of bilayered tablet
Layer I –Metformin hydrochloride CR granulation
Metformin Hydrochloride, xanthum gum/guar gum/gum tragacanth were sifted through 40
mesh sieve (stage 1).Then Povidone (K- 30) was dissolved in purified water. The materials of
stage 1 were loaded into the rapid mixer granulator and mixed for 15 Minutes at low speed.
Granules were prepared by adding binder solution to powder mixture.
The produced metformin hydrochloride granules were dried in fluidized bed dryer at 5000
c
till the loss on drying of 1.5-2.0% is achieved. Dried granules were passed through 20 mesh
sieve. Sifted granules were transferred to double cone blender. Colloidal Silicon dioxide was
sifted through 40 mesh sieve and added to above step. Magnesium stearate and Talc were
sifted through 60 mesh sieves and added to above step and mixed for 2 minutes.
Layer IІ– Pioglitazone IR (direct compression)
Pioglitazone was sifted through 30 mesh sieve. Lactose DCL 15, BHA, BHT, CCS, were
sifted through 40 mesh sieve, sunset yellow lake was sifted through 100 meshes. Mix
Pioglitazone with Lactose DCL 15 in geometrical mixing method. Then talc was sifted
through 40 # mesh and added and mixed for 5 mins. Magnesium stearate was sifted through
60 mesh sieve and mix with above step for 2 minutes at fast speed.
Compression of bilayered tablet4
Metformin hydrochloride controlled release layer and Pioglitazone with immediate release
layer granules were compressed in D- Tooling bilayer compression machine (27 stations, Cad
mach, India) using 19.2 × 8.9 mm oblong punches.

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EVALUATION PARAMETERS
Pre-formulation Studies
Fourier Transform Infrared Spectroscopy
The fourier transform infra-red analysis was conducted for the structure characterization.
FTIR spectra of the pure drug, polymers and formulations were recorded by using
BOMENMB SERIES FTIR instrument. Approximately 5mg of samples were mixed with
50mg of spectroscopic grade KBr, samples were scanned in the IR range from 500 to 3500
cm-1
, with a resolution of 4 cm-1
.
PH of the solution
The pH studies were done for both Metformin Hydrochloride and Pioglitazone by dissolving
them in their suitable solvents and determining the pH with the help of pH potentiometer.
Pre-compression studies of bilayer tablet
Angle of repose
The angle of repose was determined by the funnel method (Repos gram). The accurately
weighed drug or tablet blend was taken in a funnel. The powder was allowed to flow through
the funnel freely onto the surface. The diameter of the powder cone was measured and angle
of repose was calculated using the following equation
Tan θ = h / r
Where h = height of the pile.
r = radius of the pile.
Bulk density
Loose bulk density (LBD) and tapped bulk density (TBD) were determined by passed
through a #18 sieve to break the clumps, if any. Accurately weighed 50 g of the drug was
placed in a 100 ml graduated measuring cylinder. Initial volume was observed. The cylinder
was tapped initially 500 times from a distance of 14 + 2 mm. The tapped volume (Va) was
measured to the nearest graduated unit. The tapping was repeated additional 750 times.
Again the tap volume was measured to the nearest graduated unit. The same thing was done
for powder blend of the tablet. The LBD and TBD were calculated in g per ml using
following formulae,
Bulk density = M / V0
Where M = Mass of the sample.
V0 = Bulk volume.

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Tapped density (Td)
A weighed quantity of powder blend previously shaken to break any agglomerates
formed, was introduced in to a measuring cylinder and the volume was noted. The
cylinder was placed in the tapped density apparatus and allowed to fall under its own
weight on to a hard surface (USP-II), that provides fixed a drop of 3mm(±10%) at a
nominal rate of 250 drops per minute is used. Tapping was continued until no further
change in volume was noted. Td was calculated using the following equation;
Dt = m /Vi
Where, m = Mass of the powder.
VI = Tapped Volume of the powder.
Compressibility index
Compressibility index is an important measure that can be obtained from the bulk and tapped
densities. In theory, the less compressible a material the more flow able it is. A material
having values of less than 20 to 30 % is defined as the free flowing material.
CI = (1-Vi/V0).100
Where VI = Tapped Volume of the powder.
V0 = Bulk volume
Hausner’s Ratio
It indicates the flow properties of the powder and is measured by the ratio of tapped density
to the bulk density.
Hausners ratio = Dt/Db
Where, Dt = the tapped density,
Db = the bulk density.
Post compression studies of bilayer tablet
Physical appearance
The general appearance of tablets its visual identity and over all elegance is essential for
consumer acceptance. The control of general appearance of tablet involves measurement of
number of attributes such as tablet size, shape, color presence or absence of odour, taste,
surface texture and consistency of any identification marks.

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Tablet size and thickness
Control of physical dimensions of the tablets such as size and thickness is essential for
consumer acceptance and tablet-tablet uniformity .The diameter size and punch size of tablets
depends on the die and punches selected for making the tablets. The thickness of tablet is
measured by Vernier calipers scale. The thickness of the tablet related to the tablet hardness
and can be used an initial control parameter .Tablet thickness should be controlled within a +
or -5%. In addition thickness must be controlled to facilitate packaging.
Average weight of tablets
Take randomly 20 tablets and weigh accurately 20 tablets and calculate the average weight.
Average weight =weight of 20 tablets/20
Hardness test
This is the force required to break a tablet in diametric compression. Hardness of the tablet is
determined by Stock’s Monsanto hardness tester which consists of a barrel with a
compressible spring. The pointer moving along the gauze in the barrel which the tablet
fractures. Hardness of 5 kg considered as suitable for handling the tablet.
Uniformity of dosage units (by weight variation method)
Take randomly 30 tablets, weigh collectively and individually 30 tablets and calculate
average weight of the tablets and % assay of individual dosage units by using formula
Weight variation = Assay× Individual weight
Average wt
Friability test (As per USP)
Friability is the loss of weight of tablet in the container/package, due to removal of fine
particles from the surface. This in-process quality control test is performed to ensure the
ability of tablets to withstand the shocks during processing, handling, transportation, and
shipment. Roche friabilator was used to measure the friability of the tablets. After 100
rotations (4 minutes), the tablets were taken out from the friabilator. Permitted friability limit
is 1.0%. The percent friability was determined using the following formula.
(W1 – W2)
Friability = x 100
W1
Where, W1 = Weight of the tablet before test.
W2 = Weight of the tablets after test.

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Drug content uniformity
The tablets were assayed for the drug content using methanol as the extracting solvent. Four
tablets weighted and crushed in a mortar then weighed powder contain equivalent to 100mg of
drug transferred in 100ml methanol. The solution was diluted appropriately using pH 6.8
phosphate buffer and propanolol Hcl was estimated spectrophotometrically at 270 nm using
pH 6.8 phosphate buffer as blank.
Content of active ingredients (assay)
The amount of active ingredient(s) was determined and compared with standards stated in the
monograph. Twenty tablets were used for assay. All the batches should fall within the limit of
95 – 105 %.
In vitro dissolution
In-vitro release of the drug5
was determined by estimating the dissolution profile. Dissolution
test for pioglitazone and metformin. In vitro drug release study was carried out using USP
apparatus II at 37C± 0.5C for 1hrs, at 100rpm.0.1N Hcl (pH 1.2) was used as dissolution
medium for the first hr ,followed by pH 6.8 phosphate buffer for further 12hrs. 5 ml of
sample was withdrawn after every hour and was replaced with an equal volume of fresh
dissolution medium to maintain the equilibrium. Collected samples are analyzed by UV
spectrophotometer at 270nm and 232nm respectively for pioglitazone and metformin.
Data Analysis (Curve Fitting Analysis)
To analyze the mechanism of the drug release rate kinetics of the dosage form, the
Data obtained were plotted as:
1) Cumulative percentage drug released Vs time (Zero order plots)
2) Cumulative percentage drug released Vs Square root of time (Higuchi‘s plots)
3) Log cumulative percentage drug remaining Vs time (First order plots)
4) Log percentage drug released Vs log time (Peppas plots)
Stability studies
It is the responsibility of the manufacturers to see that the medicine reaches the consumer in
an active form. So the stability of pharmaceuticals is an important criteria. Stability of
medicinal products may be defined as the capability of a particular formulation in a specific
container to remain within its physical, chemical, microbial, therapeutic and toxicological
specification, i.e. stability of drug is its ability to resists detoriation. 90% of labeled potency

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is generally recognized as the minimum acceptable potency level. Detoriation of drug may
take several forms arising from changes in physical, chemical and microbiological properties.
The changes may affect the therapeutic value of preparation or increase its toxicity.
RESULTS AND DISCUSSION
Physical mixture of drug and polymer was characterized by FTIR spectral analysis for any
physical as well as chemical alteration of the drug characteristics. From the results, it was
concluded that there was no interference in the functional groups as the principle peaks of
the pioglitazone and metformin were found to be unaltered in the spectra of the drug-
polymer physical mixture (Figure No.1, 2).
Pre-compression Studies
All the formulations prepared by both the methods showed the angle of repose less than
30o
C, which reveals good flow property (Table No.3). The loose bulk density and tapped
bulk density for the entire formulation blend varied from 0.40 gm/cm3
to 0.782 gm/cm3
and 0.51 gm/cm3
to 0.869 gm/cm3
respectively (Table No.3). The results of Carr’s
consolidation index or compressibility index (%) for the entire formulation blend ranged
from 11.0 to 17.9%.
Post-compression Studies
The mean thickness was almost uniform in all the formulations and values ranged from 6.2
mm to 6.84 mm. The standard deviation values indicated that all the formulations were
within the range (Table No.4).
The hardness values ranged from 3.0 to 3.60 kg/cm2
for formulations were almost uniform.
Tablet hardness is not as absolute strength (Table No.4).
The hardness values ranged from 3.36 to 3.96 kg/cm2
for formulations were almost uniform.
Tablet hardness is not as absolute strength (Table No.4).
All the tablets passed weight variation test as the average percentage weight variation was
within the pharmacopoeia limits of 7.5%. It was found to be 1049 mg to 1053mg. The
weight of all the tablets was found to be uniform with low standard deviation (Table
No.4).
The drug content (Table No.5) of the tablets was found to be between 97.14 to 99.53 %.

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The results were within the range and that indicated uniformity of mixing. The cumulative
percentage drug released by each tablet in the in vitro release studies was based on the
average drug content present in the tablet.
Layer 1 – Metformin Hydrochloride
In formulation F1 the controlled layer consists of 11%, F2 consists 14%, and F3 consists 16%
of Guar gum respectively. In vitro release studies of F1, F2, and F3 incorporated with 11%,
14%, and 16% Guar gum were carried out in 6.8 phosphate buffer. All the tablet formulations
showed acceptable properties but the result of dissolution studies indicating that F1, F2, F3
released the entire drug at the end of 8hours. This might be due to slow hydration of matrix
and property of thick gel layer.
F4, F5, F6 incorporated with 11%, 14%, and 16% of Gum tragacanth also failed to meet the
needed theoretical dissolution release. This may be due to chance of bacterial contamination
that retards the swelling nature of tragacanth .So it could not sustain the release more than
8hours.
In formulation F7, F8, F9 containing xanthum gum in 11%, 14%, 16% proportions
respectively extended the drug release more than 8hours. F7 formulation with 11% of
xanthum gum extends up to 9hours with maximum release of 99.38%. F8 formulation with
14% of xanthum gum extends up to 10hours with maximum release of 98.26%.F9
formulation with 16% of xanthum gum extends up to 12hours with maximum release of
99.48%.
Increasing the percentage of polymer increase retardation of drug. This may be due to
increase of diffusion path length of the drug and strong interactions of xanthum gum
molecules with drug that leads to formation of tough complex. These results suggest that
formulation F9 with 16% xanthum gum extended up to 12hours with maximum release of
99.48%.
Layer -2 pioglitazone
In the formulation (P), immediate release layer of Pioglitazone was prepared by dry
granulation method with CCS, microcrystalline cellulose, Magnesium stearate, sunset yellow
lake. The immediate release layer consists of CCS in the conc. of 10%, where the weight of
the tablet was adjusted with microcrystalline cellulose. The release profile of Pioglitazone P

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was found to be within the limits and assay was more than 95%. Hence no further
formulation was formulated and the formulation P Was finalized as optimized formula for the
preparation of immediate release layer
Release Kinetics
F-9 shows the higher R2 value for zero order plots. This indicates that the drug releases is
concentration independent and following ‘Zero’ order kinetics. It is also expressed by
Higuchi equation and showed high linearity. To confirm the diffusion mechanism the data
were fitted in korsemayer equation with slope (n) and R2
value is 0.987. This indicates the
release of drug follows non-fickian transport. It means the release of drug from tablet is both
diffusion and dissolution mechanism. (Table No.5)
Stability Studies
The tablets from trials F9 was charged for stability at 30 o
C/ 65%RH and 40o
C/75% for two
months and the 2 months results was found to be satisfactory.
.
Table No.1: Composition of immediate release pioglitazone layer
S.NO INGREDIENTS QUANTITY(mg)
1 Pioglitazone 30
2 Micro crystalline cellulose 85
3 Crosscarmellose sodium 15
4 Magnesium state 2
5 Talc 2
6 Sunset yellow 1
Table No.2: Composition of controlled release metformin hydrochloride layer
S.NO INGREDIENTS F1 F2 F3 F4 F5 F6 F7 F8 F9
1 Metformin(mg) 500 500 500 500 500 500 500 500 500
2 PVP k 30(mg) 30 30 30 30 30 30 30 30 30
3 Tragacanth
gum(mg)
100 120 140 _ _ _ _ _ _
4 Guar gum(mg) _ _ _ 100 120 140 _ _ _
5 Xanthan
gum(mg)
_ _ _ _ _ _ 100 120 140
5 Microcrystalline
cellulose(mg)
100 100 100 100 100 100 100 100 100

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6 Lactose(mg) 120 100 80 120 100 80 120 100 80
7 Magnesium
stearate(mg) 10 10 10 10 10 10 10 10 10
8 Talc(mg) 10 10 10 10 10 10 10 10 10
9 Isopropyl
alchohol
qs qs qs qs Qs qs qs Qs Qs
Table No.3: Results of flow properties of metformin and pioglitazone layers
Formulation
code
Bulk
density(g/ml)
Tapped
density
Angle of
reposeº
Carr’s
Index (%)
Hausner
Ratio
F1 0.526 0.612 26.76 14.0 1.16
F2 0.662 0.763 27.54 13.23 1.15
F3 0.695 0.823 24.65 15.5 1.18
F4 0.782 0.869 28.68 11.0 1.11
F5 0.560 0.631 24.68 11.25 1.12
F6 0.628 0.714 25.16 14.27 1.17
F7 0.650 0.754 26.15 15.20 1.15
F8 0.566 0.789 24.12 14.40 1.12
F9 0.737 0.754 24.15 13.25 1.19
P(IR) 0.40 0.51 28.41 17.9
1.24
Table No.4: Uniformity of Thickness, Hardness, Friability, and Weight variation of
pioglitazone and metformin bilayered tablets
S.No
Formulation
code
Weight
Variation
(mg)
Uniformity
of
Thickness
(mm)
Hardness
(kg/cm3
)
Friability
%
Drug content
uniformity %
1 F1 1051 6.85 3.58 0.24 98.14
2 F2 1053 6.59 3.42 0.39 99.14
3 F3 1049 6.77 3.28 0.57 97.45
4 F4 1050 6.73 3.12 0.75 99.53
5 F5 1051 6.84 3.44 0.89 97.14
6 F6 1049 6.74 3.46 0.86 98.97
7 F7 1050 6.78 3.60 0.9 98.26
8 F8 1045 6.84 3.57 0.86 99.45
9 F9 1050 6.59 3.54 0.73 98.6
10 P(IR) - - - - 98.0

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Table No.5: In vitro release study of immediate release layer
S.NO TIME(MIN)
CUMULATIVE%
DRUG RELEASE(P)
1 5 22.705
2 10 42.1486
3 15 56.2486
4 30 65.1248
5 45 83.2497
6 60 98.854
Table No.6: In vitro release study of metformin hydrochloride controlled release layer
Cumulative % drug release
S.NO
TIME
IN
HOURS
F1 F2 F3 F4 F5 F6 F7 F8 F9
1 1 24.07 23.29 22.71 23.68 22.33 20.39 21.36 19.43 18.46
2 2 35.80 35.22 33.09 34.44 34.05 32.49 31.14 29.78 27.65
3 3 49.01 46.69 45.90 46.88 47.46 46.67 38.35 37.57 36.40
4 4 59.33 55.84 58.93 58.93 58.34 57.00 48.64 47.09 45.73
5 5 71.38 68.65 69.65 70.60 69.44 68.27 58.94 57.00 54.09
6 6 80.34 78.58 77.23 79.75 78.20 75.49 70.60 68.08 66.57
7 7 91.99 90.62 91.97 90.82 89.46 87.51 81.11 79.54 77.41
8 8 99.20 98.81 98.24 98.23 97.26 97.05 88.12 86.95 86.17
9 9 99.38 97.82 96.46
10 10 98.26 97.05
11 12 99.48
Table No.7: Stability studies of pioglitazone and metformin for 3 months
Dissolution Assay
Storage
condition
Description Pioglitazone Metformin Pioglitazone Metformin
LABLE
CLAIM
_ 30mg/tab 500mg /tab 30mg/tab 500mg/tab
Initial Complies 98.5 97.7 98.7 99.5
1st
mnth Complies 97.8 97.5 98.5 99.3
2nd
mnth Complies 96.8 96.4 97.3 98.5
3rd
mnth Complies 95.4 95.7 96.5 97.4

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Fig No.1: FT-IR spectrum of pure Pioglitazone
Fig No.2: FT-IR spectrum of pure Metformin
Figure No.3: Dissolution profiles for pioglitazone (IR) Layer

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Figure No.3: Dissolution profiles for metformin formulations F1-F9.
Table No. 8: Kinetic models of optimized batch (F9)
RELEASE KINETICS CORRELATION
COEFFICIENT(R2
)
Zero order equation 0.9865
First order equation 0.875
Higuchi(diffusion)co-efficient 0.9505
KorsmeyerPeppas equation 0.990
CONCLUSION
Success of the In vitro drug release studies recommends the product for further In vivo
studies, this may improve patient compliance. From the literature metformin HCl and
pioglitazone, individual dosage form was used in the management of diabetes mellitus.
Combination of Pioglitazone as immediate release layer and Metformin HCl as controlled
release layer improves the patient compliance. From the results formulation F9 has been
selected as best formulation among all the other formulations. Formulation F9 provides better
in vitro release from layer 2. The data obtained from in vitro release study were fitted to
various mathematical model like zero order, First order, Higuchi model and Peppas model.
The results of mathematical model fitting of data obtained indicated that, the best fit model in
all the cases the release was found to be by diffusion for optimized formulation (F9). Thus
the release of the drug from the dosage form was found to be diffusion and nonfickian
release. The formula optimized and it was selected for stability studies as per ICH guidelines.

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ACKNOWLEDGEMENT
The authors are sincerely thanks to Dr.Rajeswar Dutt and Smt.Sarojini Ramulamma College
of Pharmacy,Mahabubnagar,Andhra Pradesh.
REFERENCES
1. Gilbert S Banker, Neil R Anderson, Leon Lachman, Herberta Liebermann, Joseph L
Kanig. The theory and practice of Industrial pharmacy, 3rd edition, 1987, 293-294, 330-
331, 430-431.
2. Abraham M A, Shirwaikar A. “Formulation of multilayered sustain release tablets using
insoluble matrix system”, Indian Journal of Pharmaceutical Science, 59(6), 1997, 312-
315.
3. Snehal Khedkar. “Practical problems in developing FDCs & Bilayer tablets” WHO/FIP
Training Workshop, 2008. Email: snehalkhedkar@ipca.co.in.
4. .Alfred Martin. “Physical Pharmacy-physiochemical principles in the pharmaceutical
Sciences”, B.I Waverly Pvt. Ltd, 4th edition, 1996, 313-316.
5. Bhalala chirag ,Chauhan Sachin, Balaraman R, Seth A K, Shah Chainesh.world journal of
pharmaceutical research ,1(2) ,242-247 .
.

FORMULATION DEVELOPMENT OF METFORMIN HYDROCHLORIDE AND PIOGLITAZONE BILAYERED TABLETS USING NATURAL GUMS

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FORMULATION DEVELOPMENT OF METFORMIN HYDROCHLORIDE AND PIOGLITAZONE BILAYERED TABLETS USING NATURAL GUMS