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www.wjpr.net Vol 5, Issue 7, 2016.
1484
Deore et al. World Journal of Pharmaceutical Research
TO STUDY EFFECT OF DIFFERENT POLYMER RATIO ON DRUG
RELEASE OF BILAYER FLOATING DRUG DELIVERY SYSTEM
*1Pankaj T. Deore (B. Pharm),
2Parag D. Kothawade (M. Pharm),
3Dr. Hemant H.
Gangurde (M. Pharm, Ph. D)
1,2
Loknete Dr. J. D. Pawar College of Pharmacy, Manur, Tal- Kalwan, Dist-Nashik
(Maharashtra).
3SNJB’S Shriman Suresh Dada Jain College of Pharmacy Chandwad, Tal- Chandwad,
Nashik.
ABSTRACT
Metformin and Glimepiride are used to treat high blood sugar level
that is caused by type 2 diabetes. In type 2 diabetes, the body does not
work properly to store the excess sugar and the sugar remains in the
blood stream. With two different mode of action, the combination of
Glimepiride and Metformin HCl help the body cope with high blood
sugar more efficiently. Immediate action of Glimepiride will be helpful
to control excess sugar, which will be helpful to control excess sugar,
which will be maintained by Metformin HCl action later on.
Metformin HCl is considered to be absorbed in upper part of GIT it has
6 hours half-life and 50 to 60 % bioavailability. Therefore, an attempt
is made to retain the dosage form in the stomach for longer period of time. This is achieved
by developing Gastro Retentive Drug Delivery System i.e. Floating Drug Delivery System.
These floating tablets of Metformin HCl mainly prepared for increasing the gastric residence
time and release the drug up to 12 hrs thereby increasing the bioavailability of the drug
leading to reduced frequency of dosing. The study discusses the preparation and evaluation of
Gastroretentive bilayer tablets of Metformin HCL and Glimepiride. Immediate release layer
was formulated using sodium starch glycollate (superdisintegrant), lactose (filler), talc and
magnesium Stearate (lubricant). The effervescent based floating layers were formulated using
sodium bicarbonate along with polymer like HPMC and Xanthan gum in 3:2 ratios was
selected for formulation. Formulations F1-F3 were prepared using polymer HPMC K4M,
HPMC K15M, HPMC K4100M along with other excipients such as Xanthan gum (gelling
World Journal of Pharmaceutical Research SJIF Impact Factor 6.805
Volume 5, Issue 7, 1484-1503. Research Article ISSN 2277– 7105
*Corresponding Author
Pankaj T. Deore
Loknete Dr. J. D. Pawar
College of Pharmacy, Manur,
Tal- Kalwan, Dist-Nashik
(Maharashtra).
Article Received on
12 May 2016,
Revised on 01 June 2016,
Accepted on 22 June 2016
DOI: 10.20959/wjpr20167-6624
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agent), sodium bicarbonate (gas generating agent),citric acid (acid component), lactose
(filler) and Magnesium Stearate (lubricant). The in-vitro drug release data obtained were
subjected to different kinetic models and values of different exponent (n) and regression (R2)
were applied to know the mechanism of drug release from the formulations. Effect of
variables like the gelling polymer concentration in combination that influenced buoyancy
time, total floating time and drug release from various formulations were studied.
KEYWORDS: Metformin HCl, Glimepiride, Gastro retentive systems, Bi-layer tablet.
INTRODUCTION[1, 2]
The goal in designing sustained or controlled delivery systems is to reduce the frequency of
the dosing or to increase effectiveness of the drug by localization at the site of action,
reducing the dose required or providing uniform drug delivery. The primary objective of
sustained release drug delivery is to ensure safety and to improve efficacy of drugs as well as
patient compliance. Bi-layer tablet is suitable for sequential release of two drugs in
combination, separate two incompatible substances and also for sustained release tablet in
which one layer is immediate release as initial dose and second layer is maintenance dose.
Gastro retentive systems can remain in the gastric region for several hours and hence
significantly prolong the gastric residence time of drugs. Prolonged gastric retention
improves bioavailability, reduces drug waste, helpful for the sustained release of the drug and
improves solubility for drugs that are less soluble in a high pH environment. It has
applications also for local drug delivery to the stomach and proximal small intestines. Gastro
retention helps to provide better availability of new products with new therapeutic
possibilities and substantial benefits for patients.
Need of Floating Drug Delivery System[3, 4, 5]
Oral dosage forms pose low bioavailability problems due to their rapid gastric transition from
stomach, especially in case of drugs which are less soluble at alkaline pH of intestine.
Similarly, drugs which produce their local action in stomach get rapidly emptied and do not
get enough residence time in stomach. So, frequency of dose administration in such cases is
increased. To avoid this problem floating drug delivery system has been developed.
Certain types of drugs that benefit from using gastric retentive devices includes[6, 7]
Drugs acting locally in stomach e.g. Antacids
Drugs that are primarily absorbed in stomach e.g. Albuterol
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Drugs that are poorly soluble at an alkaline pH
Drugs with a narrow window of absorption i.e. drugs that are absorbed mainly from the
proximal small intestine e.g. Riboflavin, Levodopa
Drugs absorbed rapidly from GI tract e.g. Amoxicillin
Drugs that degrade in colon e.g. Metoprolol.
Bi-layer tablet[8, 9]
Bi-layer tablet technology for bimodal release of drug and co-administration of drugs via oral
route has been engaged a significant place in the field of drug delivery technology. In a bi-
layer configuration, the immediate release layer of the bi-layer tablet has worked as the
loading dose and the sustained release layer has maintained the therapeutic plasma drug
concentration for prolonged time.
Selection of fixed dose combination[10]
Metformin and Glimepiride are used to treat high blood sugar level that is caused by type 2
diabetes. With two different mode of action, the combination of Glimepiride and Metformin
Hydrochloride (HCl) help the body cope with high blood sugar more efficiently. Immediate
action of Glimepiride will be helpful to control excess sugar, which will be helpful to control
excess sugar, which will be maintained by Metformin HCl action later on. Thus, the
developed single tablet containing Glimepiride for immediate release and floating layer of
Metformin hydrochloride will be sufficient instead of two to three tablets of both drugs per
day, and it will also increase patient compliance and therapeutic efficacy.
MATERIALS
Metformin Hydrochloride and glimepiride obtained from Glenmark Research Centre Sinnar
Nashik. HPMC K4M, K15M & K100M were purchased from Wockhardt Pharmaceutical
Pvt. Ltd., Aurangabad Magnesium Stearate was purchased from Ozone International,
Mumbai.
SSG, Lactose, Xanthan Gum, Sodium Bicarbonate, Citric Acid & Talc were purchased from
Research-Lab Fine Chem. Industries, Mumbai.
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PREFORMULATION STUDY
UV spectroscopy study[15, 16]
Stock solutions (100µg/ml) Metformin Hydrochloride was prepared in 0.1 HCl. Stock
solutions (100µg/ml) Glimepiride was prepared in 0.1 HCl. These solutions were
appropriately diluted with the respective solvents to obtain a suitable concentration
(10µg/ml). The UV spectrum was recorded in the range 200-400 nm by using UV
spectrophotometer. The wavelength of maximum absorption (λ max) was determined.
Table 1: Concentration and Absorbance values for Metformin HCl in 0.1 HCl (λmax 242
nm)
Sr. No. Concentration (µg/ml) Absorbance
(λmax 242 nm)(Mean S.D:n=3)
1 0 0
2 2 0.108±0.012
3 4 0.242±0.011
4 6 0.351±0.013
5 8 0.471±0.011
6 10 0.601±0.012
Figure 1: Beers-Lambert’s plot for Metformin HCl
Figure 2: UV Spectrum of Metformin HCl in 0.1 N HCl
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Table 2: Concentration and Absorbance values for Glimepiride in 0.1N HCl (λmax 260
nm)
Sr. No. Concentration (µg/ml) Absorbance
(λmax 260 nm) (Mean S.D:n=3)
1 0 0
2 10 0.221±0.013
3 20 0.444±0.012
4 30 0.675±0.011
5 40 0.905±0.014
6 50 1.101±0.011
Figure 3: Beers-Lambert’s plot for Glimepiride
Figure 4: UV Spectrum of Glimepiride in 0.1 N HCl
HPLC STUDY
The samples of Metformin Hydrochloride and Glimepiride were analyze using Waters HPLC
at 23 nm, using mobile phase methanol (80%) and acetate buffer pH 3.4 (20%).
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Calibration curve of Metformin Hydrochloride in methanol
Accurately weighed quantity of Metformin Hydrochloride 100mg was dissolved in little
quantity of methanol and volume was made up to 100ml. Appropriate aliquots were taken
into different volumetric flasks and made up to 10ml with water, so as to get drug
concentrations of 100 to 500µg/ml.
Calibration curve of Glimepiride in Methanol
Accurately weighed quantity of Glimepiride 10mg was dissolved in little quantity of
Methanol and volume was made up to 100ml. Appropriate aliquots were taken into different
volumetric flasks and made up to 10ml with water, so as to get drug concentrations of 1 to
5µg/ml.
Figure 5: HPLC Chromatogram of Metformin (2.465) and Glimepiride (6.26)
Solid State Compatibility Studies of Drug with Excipients
The drug-excipients interaction study was carried out by using physical observation, FTIR
spectroscopy, DSC.
Physical observations
In this method, a small mixture of drug and excipients is placed in a vial with rubber closure,
in order to do hermetically sealed. A storage period of two weeks at 400C, 75% RH in
Environmental Test Chamber is employed after which time period; the sample is to be
observed.
Fourier transforms infrared spectroscopy (FTIR) interpretation study
To analyze the compatibility of drug and polymer the infrared spectrum of a pure Metformin
Hydrochloride and Glimepiride and combination of drug, HPMC K4M, HPMC K15M,
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HPMC K100M, Xanthan gum, sodium bicarbonate, citric acid were recorded by using
Fourier Transform Infrared Spectroscopy and the spectrum analysis was done. The IR
spectrum of the drug was compared with that of the physical mixture of Drug and excipients
to check for any possibility of drug-excipients interaction.
Differential scanning calorimetry (DSC) study
DSC analysis was performed using DSC-1 (STAR®System) on 2-5mg samples. Samples
were heated in an open aluminum pan at a rate of 100C/min conducted over a temperature
range of 30-3200C under a nitrogen flow of 2-bar pressure. Thermogram of plane drug was
compared with thermogram of polymer and drug mixture.
FORMULATION METHODOLOGY
Preparation Sustain release layer
For the preparation of sustain release layer, the active ingredient was thoroughly mixed with
polymer(s), diluent and gas forming agents using a mortar and pestle for 10 min; magnesium
stearate and talc were added to the above blend as flow promoters. In all the formulations, the
amount of Metformin hydrochloride was kept constant at 500 mg and different polymers like
HPMC K100M , HPMC K4M, HPMC K 15M, Xanthan gum were used in different ratios.
Preparation Immediate release layer
IR layer containing drug, super disintegrating agent, diluent and lubricants were mixed in
adsorption technique uniformly and compressed over SR layered tablet with hardness 5 to 8
kg cm2 to obtain bilayer floating tablets.
Tablet compression
The bilayer tablet compression was made using 12.5 mm punch in a 8 station rotary tablet
machine with single feed. In this, sustained release metformin hydrochloride blend was
introduced first in to the die cavity and a slight precompression was made so that the layer
was uniformly distributed. After that immediate release Glimepiride blend was added through
the feed and a final compression was made.
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FORMULATION AND DEVELOPMENT
STAGE I
Formulation of Metformin HCl Floating layer using factorial design
Optimization data analysis
Dependant factors (Response):
R1: Dissolution time
R2: Swelling index
R3: Floating time
Table 3: Selection of Factor and Level (All quantities in mg)
Table 4: Composition of Floating Layer (All quantities in mg)
Sr. no. Name of
ingredients T1 T2 T3 T4 T5 T6 T7 T8
1 Metformin 500 500 500 500 500 500 500 500
2 HPMC 100 100 100 100 80 80 80 80
3 Xanthan gum 53 53 67 67 53 53 67 67
4 NaHCO3 80 100 100 80 80 100 100 80
5 Citric acid 33 33 33 33 33 33 33 33
6 Lactose 34 14 00 20 54 34 20 40
7 Magnesium
Stearate 10 10 10 10 10 10 10 10
8 Talc 10 10 10 10 10 10 10 10
Total Weight 820 820 820 820 820 820 820 820
II) STAGE II
Composition of Bilayer tablet
Table 5: Composition of Bilayer tablets
IR layer
Sr. no. Name of ingredients F1 F2 F3
1 Glimepiride 2 2 2
2 SSG 4 4 4
3 Lactose 70 70 70
4 Talc 2.4 2.4 2.4
5 Magnesium Stearate 0.8 0.8 0.8
16 Colour 0.8 0.8 0.8
Coded level Independent Factors
HPMC Xanthan gum NaHCO3
Low level (-1) 80 53 80
High level (+1) 100 67 100
Floating layer
7 Metformin 500 500 500
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Precompression Properties
The granules of all sustained release formulations were evaluated for powder flow properties.
The fixed funnel method was employed to measure the angle of repose. Bulk and tapped
densities were determined by tapped density apparatus from which compressibility index and
Hausner’s ratio values were calculated and the results are given in table 7, 8, 9 & 10.
Post-Compression parameters[17]
Hardness test
Tablets require a certain amount of strength, or hardness and resistance to friability, to
withstand mechanical shocks of handling during manufacture, packaging and shipping. The
hardness of the tablets was determined using Digital Hardness tester. It is expressed in
Kg/cm2. Three tablets were randomly picked from each formulation and the mean and
standard deviation values were calculated.
Friability test
It is the phenomenon whereby tablet surfaces are damaged and/or show evidence of
lamination or breakage when subjected to mechanical shock or attrition.
The friability of tablets was determined by using Electro lab, USP EF 2 friabilator. It is
expressed in percentage (%). Ten tablets were initially weighed (Winitial) and transferred into
friabilator. The friabilator was operated at 25 RPM for 4 minutes. The tablets were weighed
again (Wfinal). The percentage friability was then calculated by,
F = 100xW
W- W
initial
finalinitial
% Friability of tablets less than 1% is considered acceptable.
8 HPMC K4M - - 100
9 HPMC K15M - 100 -
10 HPMC K 100M 100 - -
11 Xanthan gum 67 67 67
12 NaHCO3 100 100 100
13 Citric acid 33 33 33
14 Lactose 20 20 20
15 Magnesium Stearate 10 10 10
16 Talc 10 10 10
Total 900 900 900
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Weight variation test
The tablets were selected randomly from each formulation and weighed individually to check
for weight variation. The U.S Pharmacopoeia allows a little variation in the weight of a tablet.
The following percentage deviation in weight variation is allowed.
Uniformity of thickness
The thickness of individual tablet may be measured with a digital vernier calliper, which
permits accurate measurements and provides information on the variation between tablets.
Drug content
For the determination of drug content in each tablets twenty tablets were taken and crushed to
fine powder with mortal and pastel. Weight of powder equivalent to 10 mg of Metformin and
2mg of Glimepiride was taken and diluted with methanol up to 100ml in the volumetric flask.
The solution was subjected to sonication for 15minutes. Then this sonicated solution was
filtered through 0.20µm filter paper. Then the solution was assayed for drug content at
230nm using high performance liquid chromatography finally calculated drug content of
Metformin and Glimepiride.
Disintegration time
The process of breakdown of a tablet into smaller particles is called as disintegration. The in-
vitro disintegration time of a tablet was determined using disintegration test apparatus as per
I.P. The disintegration time for the tablet was determined using the disintegration apparatus.
One tablet was placed in each of six tubes placed in a beaker containing 900 ml of purified
water maintained at 37 ± 20 C and the apparatus was operated. The time taken for the tablets
to disintegrate and pass through the mesh was noted.
Determination of floating lag time (Buoyancy study)
The floating lag time is defined as the time taken by the tablet to reach the top from the
bottom of the dissolution flask. The floating lag time of tablet was determined by using a
dissolution test apparatus USP (Type II) containing 900 ml of 0.1N HCl at 37±0.5ºC.
Determination of duration of floating (In-vitro floating time)
The time for which the formulation floats constantly on the surface of the medium is known
as the duration of floating. The duration of floating of tablets were determined by using a
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dissolution test apparatus USP (Type II) containing 900 ml of 0.1N HCl at 50 rpm at
37±0.5ºC.
In vitro dissolution studies
Dissolution rate was studied by using basket apparatus (75 rpm) using 900ml of phosphate
buffer pH (6.8) as dissolution medium. The temperature of the dissolution medium was
maintained at 37 ± 20 C. Samples were determined using HPLC at 230 nm.
Determination of swelling index
The swelling of the polymers can be measured by their ability to absorb water and swell. The
swelling property of the formulation was determined by various techniques. The water uptake
study of the tablet was done using USP dissolution apparatus II. The medium used was
distilled water, 900 ml rotated at 50 rpm. The medium was maintained at 37±0.5°C
throughout the study. After a selected time intervals, the tablets were withdrawn, blotted to
remove excess water and weighed. Swelling characteristics of the tablets were expressed in
terms of water uptake by using following formula
Where, Wo= weight of tablet before immersion, Wt= weight of tablet at time t.
STABILITY STUDIES[18]
The purpose of stability testing is to provide evidence on how the quality of a drug substance
or drug product varies with time under the influence of a variety of environmental factors
such as temperature, humidity and light. The ability of a pharmaceutical product to retain its
chemical, physical, microbiological and biopharmaceutical properties within specified limits
throughout its shelf life and recommended storage conditions.
Stability testing as per ICH guidelines
Stability studies were carried out as per ICH Guidelines.
For drug products intended to be stored in Environmental Test Chamber:
Table 6: Stability Testing as per ICH Guidelines
Sr. No. Description Storage Conditions
1 Long term conditions 25
0C±2
0C and 60%RH±5%RH or 30
0C±2
0C and
65%RH±5%RH for 12 months
2 Intermediate conditions 300C±2
0C and 65%RH±5%RH for 6 months
3 Accelerated conditions 400C±2
0C and 75%RH±5%RH for 6 months
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RESULT AND DISCUSSION
Figure 6: A. FTIR Spectrum of Metformin HCl, B. FTIR Spectrum of Glimepiride, C.
FTIR Spectrum of Metformin and HPMC, D. FTIR Spectrum of Metformin and
Xanthan gum, E. FTIR Spectrum of Glimepiride and SSG, F. FTIR Spectrum of
optimized Formulation F1
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Figure 7: A. DSC Thermogram Metformin HCl, B.DSC Thermogram Glimepiride,
C. DSC Thermogram Metformin and Glimepiride
Evaluation parameters
STAGE-I
a) Precompression parameters
Table 7: Precompression parameters for floating layer of T1 to T8
Parameters T1 T2 T3 T4 T5 T6 T7 T8
Angle of repose (°) 29.12 26.31 26.25 24.51 25.22 26.13 27.91 28.23
Bulk density (g/ml) 0.53 0.58 0.52 0.59 0.52 0.55 0.56 0.59
Tapped density (g/ml) 0.62 0.65 0.66 0.65 0.61 0.61 0.65 0.69
Compressibility index 14.51 10.76 21.21 9.23 14.75 9.83 13.84 14.49
Hausner’s ratio 1.16 1.12 1.26 1.10 1.17 1.10 1.16 1.16
Bulkiness 1.88 1.72 1.92 1.69 1.92 1.81 1.78 1.69
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Post compression parameters
Table 8: Post compression parameters for floating layer of T1 to T8 (n=3)
Formulation Uniformity of
weight(mg)
Hardness
(kg/cm2)
Friability
(%) Thickness(mm)
T1 820±1.25 6.5±0.18 0.27 6.51±0.04
T2 818±1.53 6.7±0.21 0.49 6.53±0.03
T3 819±0.83 6.3±0.28 0.64 6.55±0.026
T4 822±1.46 6.2±0.31 0.35 6.50±0.015
T5 817±2.23 5.9±0.36 0.49 6.50±0.024
T6 821±1.50 6.7±0.12 0.43 6.54±0.02
T7 820±2.36 5.6±0.31 0.31 6.55±0.043
T8 819±2.03 6.3±0.16 0.38 6.53±0.031
Table 9: Post compression parameters for floating layer of T1 to T8 (n=3)
Formulation %Drug
content
Swelling
Index (%)
% Drug release
in 12 Hr
Floating lag
time(sec)
Total floating
time (Hr
T1 95±0.7 65.9±5 90±0.8 64±2 9
T2 93 ±0.5 67.3±3 89±0.9 66±3 9.5
T3 96 ±0.5 61.4±4 88±0.7 70±5 11
T4 98 ±0.7 57.7±3 85±0.6 61±2 >12
T5 97±0.83 70.8±5 91±0.9 67±4 12
T6 89±0.45 69.8±4 93±0.8 71±3 11
T7 91 ±0.7 66.9±5 95±0.6 80±5 8
T8 90±1.03 68.7±6 93±0.8 77±5 10
STAGE- II STUDY
a) IR layer
Precompression parameters for
Table 10: Precompression parameters for IR layer of F1, F2 and F3
Parameters F1 F2 F3
Angle of repose (degree) 24.8 24.6 23.9
Bulk density (g/ml) 0.454 0.456 0.455
Tapped density (g/ml) 0.512 0.532 0531
Compressibility index (%) 11.5 14.28 14.37
Hausner’s ratio 1.12 1.16 1.16
Bulkiness 2.20 2.19 2.19
b) Floating layer
Precompression parameters for Floating layer
Table 11: Precompression parameters for floating layer of F1, F2 and F3
Parameters F1 F2 F3
Angle of repose (degree) 24.11 24.17 24.56
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Bulk density (g/ml) 0.63 0.62 0.67
Tapped density (g/ml) 0.74 0.72 0.77
Compressibility index (%) 14.86 13.88 14.28
Hausner’s ratio 1.17 1.16 1.16
Bulkiness 1.58 1.61 1.49
Post compression parameters
IR Layer
Table 12: Post compression parameters IR layer (n=3) of F1, F2 and F3
Formulation Disintegration time (sec) %Drug content % CDR in 30 min
F1 67±3 98±0.6 98±0.8
F2 65±5 98±0.5 97±0.6
F3 65±4 97±0.8 96±0.9
Floating Layer
Table 13: Post compression parameters Floating layer (n=3) of F1, F2 and F3
Formulation Uniformity of
weight (mg)
Hardness
(kg/cm2)
Friability
(%) Thickness(mm)
F1 902±1.25 6.4±0.18 0.47 7.08±0.04
F2 898±1.53 6.5±0.21 0.45 7.10±0.03
F3 901±0.83 6.6±0.28 0.54 7.09±0.026
Table 14: Post compression parameters Floating layer (n=3) of F1, F2 and F3
Formulation %Drug
content
Swelling Index
(%)
Floating lag
time(sec)
otal floating
time (Hr)
F1 98±0.4 68.8±0.9 72±2 >12
F2 97±0.8 73.6±1.13 75±3 >12
F3 96±0.5 76.3±1.20 79±4 >12
Table 15: In vitro Drug release of formulation F1, F2, F3 (n=3)
Time (hrs) % C.D.R. (F1) % C.D.R.(F2) % C.D.R.(F3)
1 6.5 6.6 6.6
2 9.4 9.5 9.5
3 14.6 15.4 15.4
4 20.3 20.6 20.6
5 25.9 26.2 26.2
6 40.5 43.4 43.4
7 52.6 57.8 57.8
8 58.5 64.4 64.4
9 67.2 72.1 72.1
10 71.6 82.8 82.8
11 76.5 90.6 90.6
12 87.7 95.3 95.3
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In vitro drug release profile
The drug release profile and the effect of polymers amount on the formulation of Metformin
floating systems were determined. The HPMC K100M and Xanthan Gum sustained the
release of drug up to 12 hrs.
Figure 8: In vitro dissolution of Floating layer
Figure 9: Water uptake study
CURVE FITTING DATA
The results of In vitro release studies were also fitted into five models to investigate the
release as follows:
1. Cumulative % drug release vs. time (Zero order kinetic model).
2. log cumulative % drug retained vs. time (First order kinetic model).
3. Higuchi’s classical diffusion equation (Higuchi matrix model) in which cumulative %
release was plotted against √T (square root of time).
4. Cube root of % retained vs. time (Hixon crowell cube root law).
5. log % cumulative drug release vs. log time (Korsmeyer-Peppas model).
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Figure 10: Zero order release model of formulation F1, F2 and F3
Figure 11: First order release model of formulation F1, F2 and F3
Figure 12: Higuchi release model of formulation F1, F2 and F3
Figure 13: Hixon Crowell release model of formulation F1, F2 and F3
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Figure 14: Koremeyer-Peppas release model of formulation F1, F2 and F3
Table 16: Curve fitting data of release rate profile of formulation F1-F3
Model Formulation code
F1 F2 F3
Zero order R2 0.984 0.983 0.979
First order R2 0.910 0.904 0.856
Higuchi matrix R2 0.871 0.870 0.857
Korsmeyer-peppas R2 0.972 0.972 0.968
Hixon Crowell R2 0.965 0.964 0.947
Best fit model Zero Order Zero Order Zero Order
CURVE FITTING DATA ANALYSIS
The data obtained from in vitro dissolution studies were fitted in different kinetics models
and found to follow a pattern of zero order model as shown in table number 16, and figure no.
10 to 14. The optimized formulation F1 showed sustained and followed zero order model
(R2=0.984).
STABILITY STUDIES
Accelerated Stability Study
At the time of stability studies, the tablets of the best/optimized formulation (F1) was
subjected to evaluate for drug content uniformity, floating lag time and total floating time for
each month up to three months. The results showed that there was no more change in the
drug content, Floating Lag Time, Total floating time and % CDR of the tablets for the best
formulation (F1).
Table 17: Stability studies of bilayer floating tablet
Sr. No. Evaluation Parameters Initial
Stage
1st
month
2nd
month
3rd
Month
1 Floating Lag Time (sec) 72±2 74±3 75±4 75±3
2 Total floating time (hr) >12 >12 >12 >12
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3 Cumulative (%) DR 87 86.8 86.5 86
4 Drug Content floating layer 98±0.4 97.7±0.3 97.2±0.3 96.7±0.5
5 Drug Content IR layer 98±0.6 97.5±0.5 97±0.6 96.8±0.4
CONCLUSION
The effervescent based floating drug delivery was a promising approach to achieve in-vitro
buoyancy as the gas generated due to effervescence is trapped within the gel formed by
hydration of polymers thus decreasing the density making system buoyant. The floating
tablets containing HPMC K100M and Xanthan gum showed short buoyancy lag time with
total buoyancy time more than 12 hr due to high viscosity thick gel nature of Xanthan gum.
Optimum formulation was F1 which was combination of both gelling polymers. Formulation
F1 shows appropriate floating lag time, floating duration and sustained drug release profile.
The release was found to follow Zero order release.
Based on the experimental data and the results obtained the formulation of gastroretantive
bilayer floating tablets of Metformin HCl and Glimepiride drugs as envisaged in the research
objective has been achieved successfully.
ACKNOWLEDGEMENTS
The authors are sincerely thankful to Glenmark Research Centre Sinnar (Nashik) for
providing drug samples. I express my sincere gratitude to Dr. “Avish D. Maru” Principal
Loknete Dr. J. D. Pawar College of Pharmacy, Manur, Tal- Kalwan, Dist- Nashik for making
available all facilities to me to carry out my research work successfully.
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