International Journal of Innovative Pharmaceutical ... (1).pdf · bi-layer tablet it consist of monolithic partially coated or multilayered matrices. In the case of bi-layered tablets

RESEARCH ARTICLE Basavaraju et.al / IJIPSR / 2 (11), 2014, 2882-2897

Department of Pharmaceutics ISSN (online) 2347-2154

Available online: www.ijipsr.com November Issue 2882

FORMULATION AND EVALUATION OF BILAYER TABLETS

OF AMLODIPINE BESYLATE AND GLIMEPIRIDE

1V.D.T. Basavaraju*,

2Dr N. Srinivas

Malla reddy institute of pharmaceutical sciences, Maisammaguda, Dhulapally,

(Post Via Hakimpet, secunderabad-500014, Telangana, INDIA

Corresponding Author:

V.D.T. Basavaraju

Deparment of Pharmaceutics

Malla reddy institute of pharmaceutical sciences

Secunderabad-500014, Telangana, INDIA

Email: [email protected]

Mobile: +91 7416832013

International Journal of Innovative

Pharmaceutical Sciences and Research www.ijipsr.com

Abstract

The present work aims at formulation and evaluation of Bilayer matrixtablet that would release

Amlodipine Besilate immediately and Glimepiride as extended release. The bilayer matrix tablets were

prepared by direct compression method. Extended release layer (Glimepiride) pre compresses on

compression machine manually and on the pre compressed layer immediate release layer (Amlodipine

Besilate) was loaded and punched on compression machine automatically. Total seven batches were

prepared and powder blends before compressions were subjected for evaluation of flow properties. All

the parameters were within the limit showing good flow properties. Data from Preformulation

compatability studies suggested that there is no interaction between the excipients and the drug and the

same was confirmed from IR Spectroscopy. Weight variation test showed that the weights of all the

formulations were within Pharmacopeial limits. Drug content in all the developed formulations was

found to be uniform with sufficient hardness confirming a good mechanical strength to them. In vitro

dissolution studies had shown a satisfactory drug release from all the formulation. Based on higher in-

vitro release, F2A2 was selected as optimized formulation. The drug release from the optimized

formulation was found to follow zero order kinetics for extended release layer and first order release for

immediate release layer. The developed formulation was found to be stable during the stability studies

of three months.

Keywords: Amlodipine Besilate, Glimepiride, Direct compression method.




INTRODUCTION

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.2 There is various application of the

bi-layer tablet it consist of monolithic partially coated or multilayered matrices. In the case of bi-

layered tablets drug release can be rendered almost unidirectional if the drug can be incorporated

in the upper non-adhesive layer its delivery occurs into the whole oral cavity. From various

current methods for treating illness and diseases, chemotherapy (treatment with drugs) is the most

frequently used technique. It has the broad range of applications over the greatest variety of

disease states and is frequently the preferred treatment method [1]. For many decades, treatment

of acute disease or chronic illness has been mostly accomplished by delivery of drugs to patients

using various pharmaceutical dosage forms including tablets, capsules, pills, suppositories,

creams, ointments, liquids, aerosols and injectables as drug carriers [2,3]. However, if it is a

viable option, oral drug delivery will be chosen in all but the most exceptional circumstances.

Moreover, if the oral route is not immediately viable, pharmaceutical companies will often invest

resources in making it viable, rather than plumping for an alternative delivery system. Oral route

of drug administration have wide acceptance up to 50-60% of total dosage forms and is the most

convenient and preferred route for systemic effects due to its ease of dosing administration, pain

avoidance, accurate dosage, patient compliance and flexibility in formulation [4,5,6,7]

Conventional dosage form are accused of repetitive dosing and unpredictable absorption window

that cause wide range of fluctuation in drug concentration in the blood stream and tissues with

subsequent undesirable toxicity and poor therapeutic efficiency [8]. This dynamic such as

repetitive dosing and irratic absorption led to the concept of controlled drug delivery systems.

Formulation of layers from different polymers allows manipulation over more than one rate-

controlling polymer, thus enabling different types of drug delivery of one or more drugs, i.e.

where the drug may be released with a bolus and then at a controlled rate or by targeted drug

delivery in the GI tract using pH dependant polymers [9]. The aim in designing sustained or

controlled delivery systems is to decrease the frequency of the dosing or to increase effectiveness

of the drug by localization at the site of action, reducing the dose required or provide uniform

drug delivery. The main objective of sustained release drug delivery is to make sure safety and to

improve effectiveness of drugs as well as patient compliance. But often this controlles drug




delivery system fails to achieve the stated advantages due to lack of releasing the initial bolus

dose. dose dumping and failure to achieve site specific drug delivery [10]. Immediate release drug

delivery system is intended to disintegrate rapidly, and exhibit instant drug release. It is associated

with fluctuations in drug plasma levels, which leads to reduction or loss in drug effectiveness or

increase incidence of side effects. Administration of the DDS several times per day is therefore

necessary to compensate the decrease in drug plasma concentration due to metabolism and

excretion. A relatively constant plasma level of a drug is often preferred to maintain the drug

concentration within the therapeutic window. However, it is difficult to achieve, especially for

once-daily dosage forms, partly because the environment for drug diffusion and/or absorption

varies along the gastrointestinal (GI) tract. On the basis of these considerations, we have proposed

a bilayer tablet.[11,12].

Fig.1: Bilayer floating Tablet

MATERIALS

All Drug and chemicals used were analytical grade and procured either as gift samples or

purchased.

METHOD

Preparation of bilayer tablets

The bilayer tablets was prepared by direct compression method. Development of bilayer tablet of

Amlodipine and Glimepiride was carried out in three stages. Two layers (Immediate release layer

and controlled release layer) were formulated separately using different concentration of polymers

in different ratios. After optimization of individual layers by in-vitro studies and statistical

methods bilayer tablets was prepared using optimized formulae. Bilayer tablets were prepared on

rotary tablet compression machine. First the extended release layer was precompressed on

compression machine manually and the immediate release layer was loaded on the top of

precompressed layer and punched with 6mm punch on compression machine automatically.

Composition of immediate release and extended release are shown in below tables.




Table 1: Composition of Immediate release layer

Composition F1 F2 F3

Amlodipine besylate 5 5 5

Croscarmellose sodium 0.25 0.5 0.75

Sodium starch glycolate 2.25 2 1.75

Microcrystalline cellulose 40 40 40

Talc 2 2 2

Magnesium stearate 0.5 0.5 0.5

Total Tablet weight 50 50 50

Table 2: Composition of Extended release layer

Composition A1 A2 A3 A4 A5

Glimepiride 8 8 8 8 8

Ethyl cellulose 5 10 15 20 25

HPMC K4M 25 20 15 10 5

Microcrystalline cellulose 9.5 9.5 9.5 9.5 9.5

Talc 2 2 2 2 2

Magnesium stearate 0.5 0.5 0.5 0.5 0.5

Total Tablet weight 50 50 50 50 50

RESULT & DISCUSSION

Standard graph preparation

Preparation of stock solution:

Based on the information obtained from solubility studies of the drugs, methanol was selected as

suitable solvent for analysis. Firstly, standard stock solution (1000µg/ml) of amlodipine Besilate

was prepared by dissolving 10mg of the drug in 100ml methanol. The solution was kept for

sonication for a period of 15 min to remove any air bubbles. Similarly, the stock solution of

glimepiride (1000µg/ml) was prepared. The stock solution were individually diluted with HCL

buffer of pH 2.0 containing 0.5%w/v SLS to get final concentration of 20µg/ml each and the

diluted solutions were scanned in 200-400nm range to determine the maximum absorbance of

corresponding solution, it was found that amlodipineBesilate and glimepiride show

maximumabsorbance at 228nm and 239nm respectively.

Preparation of standard solutions:

From the above prepared stock solutions different aliquots of various concentrations (1, 2, 3, 4, 6,

8, 10, 12µg/ml) were prepared using HCL buffer pH 2.0 contain 0.5% w/v of SLS. The linearity




of the solutions was in the concentration range of 2-30µg/ml and 1-20µg/ml for amlodipine and

glimepiride respectively.

Simultaneous estimation:

The simultaneous estimation of both amlodipine and glimepiride was done by simultaneous

estimation method. Firstly, the absorptivity values of both the drugs were determined at lambda

max of amlodipine 228nm andglimepiride 239nm. The absorptivity values of the drugs is the ratio

of absorbance at selected wavelengths with the concentration of drugs in µg/ml. using the

absorptivity values a set of two simultaneous equations were framed. The stock solution of the

samples was further diluted with HCL buffer pH2.0 contain 0.5%w/v of SLS to get the standard

solution of concentration 10µg/ml.

Preparation of the standard calibration curve of Glimepiride in pH 6.8 Phosphate buffer:

Glimepiride (50mg) was dissolved in 20ml of phosphate buffer pH6.8 and volume was made up

to 100ml in volumetric flask using phosphate buffer pH6.8. from this stock solution 10ml was

withdrawn and diluted to 50ml in volumetric flask which gives the concentrations of 100µg/ml.

from this stock solution aliquots were withdrawn in volumetric flask to give concentrations of

0.2,5,10,15,20,50,and 75µg/ml. absorbance of each solution was measured at 239 nm using UV-

Vis double beam spectrophotometer with phosphate buffer pH 6.8 as reference standard.

Table 3: UV Absorbance of AmlodipineBesilate and Glimepiride in HCL buffer pH 2.0

Concentration

(µg/ml)

Absorbance

Amlodipine

Besilate (228nm)

Glimepiride

(228nm)

Amlodipine Besilate

(239nm)

Glimepiride

(239nm)

0 0 0 0 0

1 0.011±0.001 0.052±0.002 0.029±0.002 0.008±0.001

2 0.023±0.002 0.102±0.001 0.058±0.002 0.017±0.002

4 0.046±0.001 0.196±0.002 0.117±0.003 0.036±0.002

6 0.067±0.002 0.304±0.002 0.178±0.003 0.06±0.002

8 0.089±0.002 0.401±0.001 0.239±0.002 0.069±0.001

10 0.11±0.002 0.51±0.003 0.284±0.001 0.089±0.003

12 0.132±0.002 0.614±0.002 0.347±0.002 0.102±0.001

UV Absorbance values are expressed in mean±standard deviation (n=3)




Fig.2: UV Absorbance of Amlodipine Besilate and Glimepiride in HCL buffer pH 2.0

Table 4: UV Absorbance of Glimepiride in phosphate buffer pH6.8

Concentration

(µg/ml)

Absorbance

Trail 1 Trail 2 Trail 3 Mean SD

0 0 0 0 0 0

0.2 0.004 0.006 0.005 0.005 0.001

5 0.245 0.248 0.249 0.247 0.002

10 0.5 0.503 0.504 0.502 0.002

15 0.751 0.754 0.755 0.753 0.002

20 1.036 1.038 1.037 1.037 0.001

Fig.3: Standard Calibration Curve for Glimepiride in Ph 6.8 Phosphate Buffer




Drug-excipients interaction study

Fourier Transform infra-red (FTIR) spectroscopy

Table 5: Excipient Compatibility for Glimepiride

S.No. Drug+Excipients Ratio Initial

Condition

40°C/75%RH

7days 14days 30days Conclusion

1 Glimepiride+Dibasic calcium

phosphate 1:1

A white

oralmost

White

Crystallin

e

powder

Nochange Nochange Nochange compatible

2 Glimepiride+Microcrystalline

cellulose(PH101) 1:1 Nochange Nochange Nochange Compatible

3 Glimepiride+Povidone 1:1 Nochange Nochange Nochange Compatible

4 Glimepiride+Microcrystalline

cellulose(PH102) 1:1 Nochange Nochange Nochange Compatible

5 Glimepiride+MethocelK100M 1:10 Nochange Nochange Nochange Compatible

6 Glimepiride+Xanthangum 1:10 Nochange Nochange Nochange Compatible

7 Glimepiride+polymerNF1 1:10 Nochange Nochange Nochange Compatible

8 Glimepiride+polymerNF2 1:10 Nochange Nochange Nochange Compatible

9 Glimepiride+Colloidal silicon

Dioxide 1:0.25 Nochange Nochange Nochange Compatible

10 Glimepiride+StearicAcid 1:0.25 Nochange Nochange Nochange Compatible

Fig.4: FTIR Spectrum of Glimepiride Fig.5: Combined Spectrum of Glimepiride

& Excipients




Fig.6: FTIR Spectrum of Amlodipine Fig. 7: Combined spectrum of Amlodipine &

Excipients

Compressibility index:

The percentage compressibility of powder was determined using Carr‟s index. Compressibility

index lies within the acceptable range of 8.84 to 10.17. Indirectly it is showing that all the blends

having good flow properties.

Angle of repose:

The values found to be in the range of 27.91 to 28.64. All the formulations showed angle of

repose below 30° which indicated good flow properties of the blends.

Table 6: Pre compression parameters of immediate release layer

Formulation batch

Code

Angle of repose

±SD

Bulk density

(g/ml)

Tapped

density

(g/ml)

Carr's

Index (%)

Hausner's

Ratio

F1 27.95±0.72 0.454 0.498 8.84 1.1

F2 27.91±0.63 0.468 0.521 10.17 1.11

F3 28.64±0.81 0.491 0.545 9.91 1.11


The percentage compressibility of powder was determined using Carr‟s index. Compressibility index lies

within the acceptable range of 8.84 to 10.17. Indirectly it is showing that all the blends having good flow

properties.

Angle of repose:

The values found to be in the range of 27.91 to 28.64. All the formulations showed angle of repose below

30° which indicated good flow properties of the blends.




Table 7: Precompression parameters of Extended release layer

Formulation

batch Code

Angle of

repose ±SD

Bulk density

(g/ml)

Tapped density

(g/ml)

Carr's Index

(%)

Hausner's

Ratio

A1 28.13±0.43 0.465 0.518 10.23 1.11

A2 28.33±0.95 0.545 0.597 8.71 1.1

A3 29.18±0.64 0.606 0.665 8.87 1.1

A4 27.97±0.53 0.594 0.673 11.74 1.13

A5 28.53±0.77 0.486 0.541 10.17 1.11

Bulk density and tapped density:

The blends of different formulations were evaluated for bulk density and tapped density. The

results were shown in above table. The bulk density and tapped density for all the formulations of

immediate release layer varied from 0.465 to 0.606 and 0.518 to 0.673 respectively.

The values obtained were within the acceptable range and there was no large difference noticed.

With this result we can calculate the % compressibility of the powder and Hausner ratio.


The percentage compressibility of powder was determined using Carr‟s index. Compressibility

index lies within the acceptable range of 8.71 to 11.74. Indirectly it is showing that all the blends

having good flow properties.

Angle of repose:

The values found to be in the range of 27.97 to 29.18. All the formulations showed angle of

repose below 30° which indicated good flow properties of the blends.

Physical evaluation of tablets:

Uniformity of weight:

Twenty tablets were randomly selected from each formulation andevaluated. The average weight

of each formulation was shown in the above table. The values are almost uniform and were within

the USP specifications. The weights of the tablets ranged from 101±0.75mg to 101.9±0.64mg.

Thus all the formulations passed the test for weight variation.

Thickness test:

The thickness of the tablets was determined using a calibrated dial caliper and results were shown

in the above table. Tablet mean thickness is almost uniform in all the formulations and the values

obtained are from 2.49±0.01 to 2.84±0.02 mm. the standard deviation values indicated that all the

formulations werewithin the range with uniform thickness.




Hardness:

The values of hardness for tablets are ranged from 3.78±0.18 to 5.17±0.17. The lower values of

standard deviation indicates that the hardness of all the formulations were almost uniform and

possess good mechanical strength with sufficient hardness.

Friability test:

The friability of tablets were mentioned in above table. The values ranged from 0.40 to 0.69. All

the values are below 1% indicates that the tablets of all the formulations are having good

withstanding property.

Disintegration time:

The disintegration test was performed for immediate releaselayer of all formulations. The DT

recorded for F1, F2, F3 formulations was 36, 30 and 75 sec respectively.

Drug content analysis:

The content uniformity test was performed for all formulations and results were shown in above

table. Three replicates from each test were recorded. The mean and SD of all the formulations are

calculated. The drug content of amlodipine of tablets in HCl buffer ph. 2.0 was to be between

91.16±0.96 to 95.89±0.71. The drug content of glimepiride of tablets in HCl buffer ph. 2.0 was

found between 92.13±0.98 to 96.48±0.86. The drug content of glimepiride layer of tablets in

phosphate buffer ph. 6.8 was to be between 92.18±0.53 to 96.60±0.84. The cumulative % drug

released by each formulation in vitro release studies was calculated on mean content of the drug

present in the respective tablet in the respective dissolution medium.

Table 8: Physico chemical characteristics of bilayer matrix tablets

Formulation

batch Code

Average

Weight

(mg)±SD

Hardness(Kg

/cm2)±SD

Thickness(

mm)±SD

Friability

(%)

Disintegration time for

Amlodipine layer(sec)

F1A1 101.4±0.86 3.78±0.18 2.75±0.01 0.58 36±1.53

F1A2 101.4±1.07 4.28±0.17 2.84±0.02 0.69 36±1.53

F1A3 101.7±0.98 4.23±0.18 2.49±0.01 0.62 36±1

F1A4 101.9±0.64 5.17±0.17 2.72±0.01 0.54 36±1.53

F1A5 101.5±0.8 3.82±0.12 2.61±0.01 0.4 36±1

F2A2 101±0.75 5.13±0.15 2.52±0.01 0.58 30±1

F3A2 101.7±1.47 5.17±0.17 2.5±0.01 0.47 75±1.53




Table 9: Drug content analysis of Bilayer Matrix Tablet

Formulation batch

Code

Drug content in pH2.0 HCl buffer ± SD Drug content in Ph6.8

phosphate buffer ± SD

AmlodipineBesilate Glimepiride Glimepiride

F1A1 93.20±0.78 92.13±0.98 93.10±0.79

F1A2 95.38±1.28 96.48±0.86 96.6±0.84

F1A3 91.16±0.96 95.22±0.88 94.93±0.73

F1A4 93.68±0.76 92.65±0.64 95.54±0.81

F1A5 92.98±0.94 93.11±1.42 92.18±0.53

F2A2 95.89±0.71 95.86±0.76 96.29±0.68

F3A2 93.31±0.87 94.85±0.75 94.40±0.81

In vitro drug release study:

The in vitro study was carried out using USP dissolution apparatus II (paddle type) and results

were shown in below table.

From the dissolution profile of all the extended release formulations (A1-A5), it was found that

the formulations A2, A3, A5 showed drug release up to 12hrs. In these three formulations A2

showed best release profile when compared to the other two formulations. The formulation A1

and A4 showed their release profile up to 11hrs only. It is because of the presence of more

amount of hydrophilic matrix in A1 formulation. Faster release of drug from the hydrophilic

matrix was probably due to gel effect, erosion effect. A4 formulation released drug up to 11h

higher release rate because of higher fraction of ethyl cellulose is in comparison to HPMC. Due to

the insufficient amount of HPMC, the gaps formed in the matrix system were not filled properly

and diffuse out through the pores. Formulation A2 contain ethyl cellulose (2%) and HPMC (4%)

Showed Maximum Delayed Release. Possibly swelled gel of HPMC might have packed

sufficiently the aforementioned cracks. The drug release of A2 formulation in 2 and 12 hrs was

19.36% and 84.26% respectively.

From the dissolution profile of all immediate release formulations (F1-F3), it was found that F2

formulation showed faster release. It has 1%croscarmellose sodium and 4% sodium starch

glycolate used in the allowable range. The drug released was 89.52% within 60min. F1

formulation showed 85.31% drug release within 60min because of presence of less % of

croscarmellose sodium. F3 formulation showed 81.91% drug release with in 60min because of

excess Superdisintegrants. Comparative in vitro drug release pattern of immediate release layers

of amlodipine was shown in below figure. The extended release formulations A3 and immediate




release formulation F2 showed best release. Hence we chooses F2A2 as the optimized

formulation for further studies.

Table 10: In vitro drug Release profile of Immediate Release Layer (%CDR)

In vitro drug Release profile of Immediate Release Layer (%CDR)

Time (Min) F1 F2 F3

5 35.08 40.84 30.38

10 46.7 52.81 42.8

15 57.53 62.57 53.19

20 63.47 67.18 60.78

30 72.48 75.58 67.16

45 80.14 84.16 76.61

60 85.31 89.52 81.91

Table 11: In vitro drug Release profile of Extended Release Layer (%CDR)

In vitro drug Release profile of Extended Release Layer (%CDR)

Time (Hrs) A1 A2 A3 A4 A5

0 0 0 0 0 0

1 20.16 12.86 15.91 20.65 17.32

2 29.08 19.36 24.53 31.16 27.56

3 37.73 26.03 31.08 41.08 36.18

4 45.48 33.38 39.38 49.98 44.63

5 53.23 40.19 46.23 60.08 52.38

6 61.18 47.51 53.16 69.21 59.87

7 68.36 54.23 59.7 77.73 67.08

8 76.56 61.11 66.83 83.83 74.44

9 82.28 68.18 74.11 90.51 80.36

10 89.03 74.31 78.39 94.98 86.53

11 94.16 79.05 84.86 99.48 91.45

12

84.26 89.63

96.89

Release kinetics:

The release profile of extended release layer of glimepiride of all formulations were compared

with zero order, first order, higuchi model and korsemeyer –Peppas model in the below table. The

data were processed for regression analysis.

The data was evaluated for zero order, first order, higuchi model and korsemeyer –Peppas model,

the R2 values obtained were shown below table. The data suggested that release kinetics of

glimepiride from A1 to A5 follow zero order drug release, because the values of regression

coefficient obtained for zero order release profiles are higher as compared to first order and

higuchi plot. The mechanism involved in the release of drug from polymer matrix traced by




comparing the n values of formulations which obtained from kosermeyer-peppas model. The n

values were in between the range of 0.5 to 1.0.

The release profiles of immediate release layer of amlodipine Besilate of all formulations were

compared to zero order and first order.

The data was evaluated for first order and zero order. The R2 values obtained were as shown in

below figure. The data suggested that release kinetics of amlodipine from F1 to F3 seem to follow

first order drug release because the values of regression coefficient obtained for first order release

profiles are higher as compared to zero order.

Table 12: Release kinetics of immediate release layer

Release kinetics of Immediate release layer

Formulation Zero order Plot First order Plot Best fit Model

R2 R2

F1 0.745 0.953 First order



Table 13: Release kinetics of extended release layer

Release kinetics of Extended release layer

Formulation Zero order

Plot

First order

Plot

Higuchi

Matrix

Korsmeyer

Peppas

Best fit

Model

R2 R

2 R

2 n R

2

A1 0.9808 0.924 0.9773 0.6917 0.9957 Zero Order

A2 0.9946 0.9666 0.9528 0.7891 0.9946 Zero Order

A3 0.9871 0.9555 0.9701 0.7128 0.997 Zero Order

A4 0.9797 0.8023 0.9785 0.6889 0.9974 Zero Order

A5 0.9802 0.8958 0.9756 0.7023 0.9996 Zero Order

Stability studies:

The accelerated stability studies were carried out according to ICH guidelines. Optimized

formulation F2A2 was packed in strips of aluminum foil laminated with PVC by strip packing

and this packed formulation was stored in ICH certified stability chambers maintained at 40°C

and 75% rh ?(zone III) for 3months. The tablets were evaluated before and after one month of

stabilization for the drug content, friability, hardness, DT and in-vitro release. After a period of 3

months, the samples were observed for any change in appearance of tablet and no change in the

appearance of tablet was noted. The drug content of amlodipine andglimepiride in the formulation

was found to be 94.18±0.93, 95.32±0.64 and 94.76±0.75 which showed slight decrease in drug




content but statistically insignificant. The results were tabulated below. The formulation F2A2

was found to be stable in terms of drug content and slight decrease in hardness and increase in

friability were observed, while the in vitro release profile is shown in below tables. The invitro

release profile of F2A2 formulation initially and after 3 months was almost comparable and there

was no much difference observed. Thus the developed formulation was found to be stable at

given storage conditions.

Table 14: Physico chemical characteristics of optimised formulation stored at 40°C/75%RH

Physico chemical characteristics of optimised formulation stored at 40°C/75%RH

F2A2 0 Days 90 Days

Friability 0.58 0.81

Hardness 4.33±0.854 4.15±0.683

Disintegration time 30±1 33±1.52

Table 15: Drug content analysis stored at 40°C/75%RH%RH

Drug content analysis stored at 40°C/75%RH

Drug

content

Pioglitazone in HCL

Buffer

Glimepiride in HCl

Buffer

Glimepiride in Phosphate

Buffer

0 Days 95.89±0.596 96.86±0.854 96.29±0.712

90 Days 94.18±0.926 95.32±0.641 94.76±0.753

Table 16: In-vitro drug release profile of Formulation of F2 Layer stored at 40°C/75%RH

In-vitro drug release profile of Formulation of F2 Layer stored at 40°C/75%RH

Time (Min) 0 Days 30 Days 60 Days 90 Days

0 0 0 0 0

5 40.84 39.56 38.67 37.76

10 52.81 51.72 50.68 49.51

15 62.57 61.65 60.42 59.62

20 67.18 66.28 65.26 64.12

30 75.58 74.64 73.72 72.55

45 84.16 83.28 82.12 81.27

60 89.52 88.42 87.55 86.65

Fig. 8: Comparative invitro drug release profiles of formulation of F2 layer stored at

40°C/75%RH




Table 17: In-vitro drug release profile of Formulation of A2 Layer stored at 40°C/75%RH

In-vitro drug release profile of Formulation of A2 Layer stored at 40°C/75%RH

Time (Hrs ) 0 Days 30 Days 60 Days 90 Days

0 0 0 0 0

1 12.86 13.68 14.46 15.23

2 19.36 20.23 21.38 22.18

3 26.03 27.18 28.25 29.07

4 33.38 34.25 35.13 36.19

5 40.19 41.32 42.56 43.41

6 47.51 48.38 49.25 50.12

7 54.23 55.36 56.15 57.01

8 61.11 62.26 63.42 64.31

9 68.18 69.31 70.15 71.11

10 74.31 75.23 76.37 77.24

11 79.05 80.23 81.31 82.15

12 84.26 85.38 86.15 87.21

Fig 9: Comparative invitro drug release profiles of formulation of A2 layer stored at

40°C/75%RH

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International Journal of Innovative Pharmaceutical ... (1).pdf · bi-layer tablet it consist of monolithic partially coated or multilayered matrices. In the case of bi-layered tablets