to study effect of different polymer ratio on drug …

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).


1500


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.

REFERENCES

1. Jain K. Dinesh Novel Drug Delivery System, Nirali Prakashan, 1st Edition, 2102; 11.2-

11.39.

2. Jain N. K, Novel Drug Delivery System, CBS Publishers Delhi, 2nd

Edition, 2004; 1-42.

3. http://bbriefings.com/pdf/17/ACF8D8E.pdf

4. shodh.inflibnet.ac.in/bitstream/123456789/166/2/02_introduction.pdf

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to study effect of different polymer ratio on drug …

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