AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL … · Repaglinide requires frequent dosing before meals due to short ... Effect of different variables was checked by ... The harness of

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Sunil et al. / Pharma Science Monitor 8(3), Jul-Sep 2017, 355-374

Pharma Science Monitor 8(3), Jul-Sep 2017

FORMULATION AND DEVELOPMENT OF REPAGLINIDE GASTRO RETENTIVE

FLOATING TABLETS

Sunil Patel*, Sanjesh Rathi, Pragnesh patani, Hardeep Banwait

Department of Pharmaceutics, A-one pharmacy college, Anasan. Gujarat.

ABSTRACTGastroretentive dosage forms have potential for use as controlled release drug delivery systems.A Controlled release system designed to increase its residence time in stomach without contactwith mucosa was achieved through the preparation of repaglinide floating tablets by directcompression method. In the present study, repaglinide an anti-diabetic agent was formulated intofloating tablets by direct compression method using polymers such as different grades ofHydroxypropyl methylcellulose (HPMC) polymers such as HPMC K4M, K15M and K100M,sodium alginate and Carbopol 934P. Sodium bicarbonate was used as gas generating agent. Thefloating tablets were evaluated for their physico-chemical properties, in-vitro release and stabilitystudies. The order of Swelling index was found to be Carbopol 934P > sodium alginate > HPMCK100M > HPMC K15M > HPMC K4M. Sodium bicarbonate at the concentration of 14 %w/wwas found to be ideal in achieving the buoyancy. The buoyancy lag time was found to be lessthan 1 minute. In all the five formulations prepared, formulation F4 (sodium alginate) wasselected as best formulation as it released 80.12% of drug in a period of 12 hrs. Tablets followeddiffusion controlled first order kinetics.KEYWORDS: Repaglinide, HPMC, Carbopol 934P, Buoyancy, Swelling index, In-vitrorelease.

INTRODUCTION

Oral route of administration is most convenient & preferred route of administration among

various other delivery system. More than 70% of drugs are available in market in form of oral

drug delivery system due to pain avoidance & versatility. Dysphagia is commonly found among

all age groups. [1,2] Gastrointestinal tract targeting dosage forms are prepared to release drug at

gastrointestinal site. Several types of gastrointestinal target dosage forms including intragastric

floating system, high density system, mucoadhesive system that gets adhere to gastric mucosal

surface to extend GRT, magnetic system & unfordable extendible or swellable systems have

been developed. Floating drug delivery system is useful for several categories of drugs which act

locally in stomach, poorly soluble in alkaline pH, having narrow window of absorption, unstable

in intestine or colonic environment & primarily absorbed in stomach. Drugs having solubility in

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acidic medium & higher absorption in upper part of intestine can be used to deliver through

floating system.[3]

Repaglinide is oral hypoglycaemic agent & first member of meglitinide class, used to treat type-

2 diabetes mellitus. It blocks ATP dependent potassium channel to stimulate release of insulin by

binding to specific site on pancreatic b-cells. Repaglinide lowers blood glucose by stimulating

release of insulin from pancreas. It achieves this by closing ATP-dependent potassium channels

in membrane of beta cells. This depolarizes beta cells, opening cells calcium channels, &

resulting calcium influx induces insulin secretion. Its short half-life (1hr), dosing frequency (two

to four times day) & local action in stomach make repaglinide ideal candidate for floating drug

delivery system. Repaglinide requires frequent dosing before meals due to short half-life & there

by imposing side effects such as skeletal muscles pain, headache & git effects. Floating tablets

with anti-diabetic drug, increase effectiveness & release of drug in control manner from

polymeric membrane & thereby, maintain its concentration for longer duration. Due to short

lasting action, fast clearance, enzymatic stability & absorption throughout it make repaglinide

suitable target for developing gastroretentive dosage form.

MATERIALS & METHODOLOGY

Repaglinide was obtained from Indoco remedies Ltd. Carbopol and HPMC K100 M were

obtained from Sulab Laboratory, Vadodara. Other ingredients and excipients used were

laboratory analytical grade.

Preformulation of Drug[4,5,6,7]

The Preformulation study is mostly generate data useful to develop stable dosage forms that can

be mass-produced for manufacturer. Physical examine was done to check Organoleptic

Characteristics of Repaglinide like color & odor. The melting point of Repaglinide was

determined by capillary method using melting point apparatus. It will be determined by

saturating 10 ml of n-octanol with 10ml 0.1 N HCL in separating funnel for 24 hrs. 10mg of drug

as added into separating funnel & intermediate shaking will be done for 4 hrs. Solvent layers was

separated through funnel & amount of drug dissolved in each phase was determined 248 nm

against blank. The solubility of Repaglinide was determined in methanol, ethanol, propanol,

butanol, propylene glycol & water. Excess quantity of Repaglinide was added to each vial

containing 1 ml of solvent. Mixture will be stirred & sonicated to facilitate proper mixing of

drug. Mixture was shaken for 72 hrs at 40±0.5°C in rotary orbital shaker (REMI, Mumbai).

Mixture will be then allow to stand for 24 h to attain equilibrium. Further mixture was

centrifuged at 3000 rpm for 15 min, followed by filtration through whattman filter paper.



Filtrates was diluted with 0.1 N HCL & quantified by UV Spectrophotometry at 231 nm.

Calibration curve for estimation of drug was constructed employing 0.1 N HCL as medium.

Stock solution of repaglinide (100μg/mL) prepared in methanol, was subsequently diluted with

distilled water to obtain series of dilutions containing 1, 2, 4, 6, 8, 10, 20 & 30 μg/mL of drug.

Absorbances of above dilutions were measured using UV-Visible spectrophotometer at λmax of

231 nm. These Calibration curves were used for estimation of repaglinide in present study.

Potassium bromide IR disc was prepared using Repaglinide, Ethyl cellulose, HPMC, Carbopol

934 & mixture on Hydraulic Pellet press will be scanned 4000-400 cm-1 region in FTIR &

obtained IR Spectrum was compared with reference spectrum of Repaglinide. Thermal analysis

of Drug Repaglinide & polymers will be studied employing differential scanning calorimetry

which was done to check compatibility for Floating Tablets formulations.

Formulation & Development of Repaglinide floating tablets by using DoE Approach

Repaglinide Floating Tablets was formulated using various Drug: Polymer ratio, polymer

concentration, type of floating agent, stirring time, concentration floating agent & evaluated for

floating time, buoyancy time & drug release profile for preliminary selection to develop DoE

approach. Risk assessments had been done to select formulation & process variable which may

affect product quality for CQAs by process characterization that defines satisfactory changes in

material & process parameters. Finally, this can result in quality assurance by Process Design

Space to understand & develop control strategy. Critical quality attributes was categorized into

high, medium & low risk parameters based on knowledge space. Usually high risk parameters

are considered important for Design of Experiments as they are having more effect than others &

need to be in accepting multivariate ranges. Effect of different variables was checked by floating

time, buoyancy time & % CDR characterization of floating agent formulated in Preliminary trial

batches. Based on that characterization, CQAs will be selected which affect highly on floating

agent Formulation.

Characterization of Repaglinide floating tablets

Precompression Parameters [8-11]

Angle of Repose:

Take required quantity of blend & poured into hollow cylinder which was placed on graph sheet.

Then cylinder was slowly lifted. Then height & diameter of heap formed was being note down.

Angle of repose (θ) was calculated by formula:

θ = tan-1 (h/r)

Where,



h = Height of pile

r = Radius of pile

Bulk Density:

Blend will be weighed & transfer to measuring cylinder. Then bulk volume is noted. Bulk

density is being calculated by using following formula:

Bulk density = W/V0 g/ml

W= Mass of blend

V0 =Untapped volume

Tapped Density:

Tapped density will be measured by transferring known quantity of blend into graduated cylinder

& was placed on tapped density apparatus. Initial volume will be noted. Apparatus was set for

500 taps. Tapped density will be determined as ratio of mass of blend to tapped volume.

Tapped density=W/Vf g/ml

Where,

W= Mass of blend

Vf = Tapped volume

Carr’s Index:

It is measured by tapped density apparatus for 500 taps for which difference should be not more

than 2%. Based on apparent bulk density & tapped density Carr’s index will be calculated by

using following formula:

Carr’s index = [(V0 – Vf) / V0] X 100

Hausner’s ratio:

It indicates flow properties of powder. Ratio of tapped density to bulk density of powders is

called Hausner’s ratio.

Hausner’s ratio= Tapped density / Bulk density

Post compression evaluation [12-14]

Hardness Test:

The harness of tablet will be determined using Monsanto hardness tester. Three tablets will be

randomly selected & hardness of tablet will be measured.

Diameter & Thickness:

The diameter & thickness of tablet will be measured by using Vernier calliper.

Disintegration Time:



The DT of tablet will be determined as per IP. Tablets will placed in DT tubes & time required

for complete disintegration, that is without leaving any residues on screen is recorded as

disintegration time.

Weight Variation Test:

Weight variation test will be conducted as per IP.20 Tablets were selected form batch.

Friability:

Twenty tablets will be weighed accurately & placed in tumbling apparatus that revolves at 25

rpm. After 4 min., tablets will be weighed & percentage loss in tablet weight was determined.

Drug content:

Twenty tablets are powdered, & equivalent weight powder was accurately weighed & transfer

into 100 ml volumetric flask. Initially, 5 ml methanol is added & shaken for 10 min. Then,

volume is made up to100 ml with 0.1N Hydrochloric acid. Solution in volumetric flask is filter,

dilute suitably & analyze spectrophotometrically.

In –Vitro Floating Lag time & Buoyancy Time:

The randomly selected tablets will kept in 100 ml beaker containing simulated gastric fluid pH

1.2 as per USP. Time taken for tablet rise to surface & float will be taken as floating time.

Duration of time dosage form constantly remained on surface of medium will be determined as

total floating time.

In –Vitro Dissolution Studies:

The release rate of tablet will be determined by using USP type-1 apparatus (Basket type). test

will performed by using 900 ml of 0.1 N HCL as dissolution medium at 37 +0.5 oc. 10 ml will be

withdrawn after each interval & replace with fresh medium. Amt. of drug release will be

measured by using standard calibration curve of PCM.

The kinetic release study will performed to find drug release mechanism from dissolution

parameter by using different various kinetic model equations. The conventional marketed

formulation will be compare with optimized Tablets. The drug or dosage form quality may affect

under impact of by varying temperature, humidity & light with time which can be found out by

stability testing. It can be carried out at 25°C ± 2°C/ 60% RH ± 5% RH & 40°C ± 2°C/ 75% RH

± 5% RH for selected formulation for three months. Samples were withdrawn on 0th, 30th, 60th

& 90th day & were analyzed for physical appearance & drug content.

RESULTS AND DISCUSSION

The pure drug Repaglinide & various other excipients were subjected to various preformulation

parameters such as organoleptic characteristic study, Melting Point Determination, solubility



study Wavelengthmax (λmax) Determination, Calibration curve, Identification of Drug by

Repaglinide, DSC study & FT-IR study. The colour of Repaglinide was visualized white with

odourless or with faint characteristic odor having white crystalline powder appearance. The IR

spectrum of standard drug Repaglinide & other ingredients shows same peak, functional group at

difference frequency shown in figure 2-5. Results revealed no changes seen in IR peaks of

Repaglinide, when mixed with polymers. These observations indicate compatibility of polymers

with Repaglinide. The DSC of standard drug Repaglinide & other ingredients shows same peak,

functional group at difference frequency shown in figure 7. Results revealed no changes seen in

DSC peaks of Repaglinide, when mixed with polymers. These observations indicate

compatibility of polymers with Repaglinide.

Selection of Formulation & Process Variables of Preliminary Trial Batches of Repaglinide

Floating tablets

Table 1: Formulation Design of Trial batches for Repaglinide Floating tablets

Batch No. Polymer Type

Polymer

concentration

(%)

Repaglinide

(mg)

EFFECT OF TYPE OF POLYMER

RPFT1 HPMC K4M 10 10

RPFT 2 HPMC K100M 10 10

RPFT 3 CARBOPOL 10 10

RPFT 4 XANTHUM GUM 10 10

EFFECT OF CONCENTRATION OF CARBOPOL





EFFECT OF CONCENTRATION OF HPMC L100M






Characterization of batches RPFT1- RPFT4.

Figure 1: Effect of type of polymer

From result of trail batches we can conclude that HPMC shows fast floating lag time than

carbopol & Xanthan gum. Swelling index of HPMC is also high than carbopol. Thus, HPMC

K100M & Carbopol was selected for further study.

Figure 2: Effect of conc. of carbopol

From result of trail batches we can conclude that as Carbopol concentration increases, buoyancy

lag time, total floating time & swelling index also increases. Thus, 10-20 % Carbopol was

selected for further study.

0

50

100

150

200

250

300

350

RPFT1 RPFT 2 RPFT 3 RPFT 4

EFFECT OF TYPE OF POLYMER

Buoyancy lag time (s) Total floating time (h) Swelling index (%)

0

50

100

150

200

250

RPFT5 RPFT 6 RPFT7 RPFT 8

Effect of conc. of carbopol




Figure 3: Effect of type of HPMC K100M

From result of trail batches we can conclude that as HPMC K100M concentration increases,

buoyancy lag time, total floating time & swelling index also increases. Thus, 15-25 % HPMC

K100M was selected for further study.

% Cumulative Drug Release Study of Batches LMLC1-LMLC9

Figure 4: % Cumulative Drug Release Study of Batches RPFT1-RPFT11

Risk Assessment of Critical Quality Attributes from Preliminary trial Batches to Develop

DoE Approach:

Critical quality attributes are categorized in high, medium & low risk parameters based on

knowledge space to check influence of formulation & process parameters. Usually high risk

parameters are considered important for Design of Experiments as they are having more effect

050

100150200250300350400


Effect of conc. of HPMC K100M

RPFT9 RPFT 10 RPFT 11

-20

0

20

40

60

80

100

120

0 2 4 6 8 10 12 14

Cummulative drug release (%)( 12 Hr.)

RPFT1 RPFT2 RPFT3 RPFT4 RPFT5 RPFT6

RPFT7 RPFT8 RPFT9 RPFT10 RPFT11



than others & need to be in accepted multivariate ranges. Critical parameters & critical quality

attributes (CQAs) for selection of optimum formulation are shown.

Formulation & Development of Repaglinide floating tablets by using 32 Factorial Design

Approach

Table 2: 32Factorial Batches

Independent Variables of Formulations

Independent Variables Low(-1) Medium (0) High(+1)

Carbopol Concentration

(%) (X1)10 15 20

HPMC K100M Concentration (%)

(X2)10 20 30

Dependent Variables

Y1- Buoyancy lag time (s)

Y2- Total floating time (h)

Y3- Release after 12 hours (%CDR)

Characterization of Batches RPGFT1- RPGFT 9

Figure 5: Characterization Batches RPGFT1 – RPGFT9

0

20

40

60

80

100

120

RPGFT 1 RPGFT 2 RPGFT 3 RPGFT 4 RPGFT 5 RPGFT 6 RPGFT 7 RPGFT 8 RPGFT 9

Characteristics of RPGFT1-RPGFT9

Buoyancy -% (Y1) Total Floating Time (Y2) Drug release after 12 hr (Y3)



% Cumulative Drug Release profile

Figure 6: % Cumulative Drug Release profile of Batches RPGFT1 – RPGFT9

Release Kinetic

The mechanism was analyzed with support of PCP V2.08 dissolution software using as shown

Table 31. By plotting values of Higuchi model, near straight lines with parallel positive slopes

were obtained representing that, best fit model for formulations was Higuchi model.

Statistical Analysis

Statistical analysis had done by Design expert software version 9.0.2.0. & generated first order

polynomial equations. From preliminary results, 32 full factorial design was utilized in which

four factors were evaluated, separately at three levels & possible nine combinations were

formulated. Three level factorial study was carried out using four different variable. In first

factorial design, Carbopol Concentration (X1) & HPMC concentration (X2) were taken as

independent variables while % buoyancy (Y1), total floating time (Y2), and Drug release after 12

hr. (Y3) were selected as dependent variables for both factorial designs. Full model was found

insignificant so reduced model was applied for all four independent variables & detailed

ANOVA, Response Surface Counter Plot & 3 D plot are as follows:

Effect on % buoyancy (Y1) - Surface Response Study

The positive value of coefficient of X1 in equation indicates decrease in buoyancy with Polymer

Concentration.

Final Equation in Terms of Actual Factors:

Buoyancy lag time = +116.25500 - 1.74100 * Carbopol Concentration - 0.22567 * HPMC

K100M Concentration

0

20

40

60

80

100

120

0 2 4 6 8 10 12 14

%CD

R

time (hrs.)

% Cumulative Drug Release profile of BatchesRPGFT1 – RPGFT9



Table 3: ANOVA Table for Response Y1

ANOVA for Response Surface Linear model

Analysis of variance table [Partial sum of squares - Type III]

Sum of Mean F p-value

Source Squares df Square Value Prob >

F

Model 485.22 2 242.61 1292.09 <

0.0001

significant

A-Carbopol Concentration 454.66 1 454.66 2421.46 <

0.0001

B-HPMC K100M

Concentration

30.56 1 30.56 162.73 <

0.0001

Residual 1.13 6 0.19

Cor Total 486.34 8

(a) (b)

Figure 7: Response Surface Plot

Effect on Total Floating Time (Y2) - Surface Response Study

The positive value of coefficient of X1 in equation indicates increase in floating time with X1.


Design-Expert® SoftwareFactor Coding: ActualBuoyancy lag time (Sec.)

Design points above predicted valueDesign points below predicted value96.79

75.39

X1 = A: Carbopol ConcentrationX2 = B: HPMC K100M Concentration

10

15

20

25

30

10

12

14

16

18

20

70

75

80

85

90

95

100

Bu

oy

an

cy

la

g t

ime

(S

ec

.)

A: Carbopol Concentration (%)

B: HPMC K100M Concentration (%)

Design-Expert® SoftwareFactor Coding: ActualBuoyancy lag time (Sec.)


75.39

X1 = B: HPMC K100M ConcentrationX2 = A: Carbopol Concentration

10

12

14

16

18

20

10

15

20

25

30

70

75

80

85

90

95

100

Bu

oy

an

cy

la

g t

ime

(S

ec

.)





Total floating time = +0.95556 +1.06667 * Carbopol Concentration +0.076667* HPMC

K100M Concentration





Source Squares df Square Value Prob > F

Model 174.19 2 87.10 14.82 0.0048 significant

A-Carbopol Concentration 170.67 1 170.67 29.05 0.0017

B-HPMC K100M Concentration 3.53 1 3.53 0.60 0.4679

Residual 35.26 6 5.88

Cor Total 209.45 8

(a)

(b)

Figure 8: 3D Surface Plot

Design-Expert® SoftwareFactor Coding: ActualTotal floating time (h)


10.7


10

15

20

25

30

10

12

14

16

18

20

10

15

20

25

30

To

tal

flo

ati

ng

tim

e (

h)

A: Carbopol Concentration (%)B: HPMC K100M Concentration (%)

Design-Expert® SoftwareFactor Coding: ActualTotal floating time (h)


10.7


10

12

14

16

18

20

10

15

20

25

30

10

15

20

25

30

To

tal

flo

ati

ng

tim

e (

h)

B: HPMC K100M Concentration (%)A: Carbopol Concentration (%)



Effect on Release after 12 Hr. (Y3) - Surface Response Study

The Negative value of coefficient of X1 in equation indicates decrease drug release with Polymer

Concentration. Negative value of coefficient of X2 indicates decrease in Release after 12 Hr...


Release after 12 Hr. = +108.60000 -2.24667 * Carbopol Concentration -0.07200 *

HPMC K100M Concentration





Source Squares df Square Value Prob > F

Model 760.24 2 380.12 10.76 0.0104 significant

A-Carbopol Concentration 757.13 1 757.13 21.44 0.0036

B-HPMC K100M Concentration 3.11 1 3.11 0.088 0.7767

Residual 211.92 6 35.32

Cor Total 972.16 8

(a) (b)

Figure 9: 3D Surface Plot

Design-Expert® SoftwareFactor Coding: ActualRelease after 12 Hr. (%)


57.1


10

15

20

25

30

10

12

14

16

18

20

50

60

70

80

90

100

Re

lea

se

aft

er

12

Hr.

(%

)



Design-Expert® SoftwareFactor Coding: ActualRelease after 12 Hr. (%)


57.1


10

12

14

16

18

20

10

15

20

25

30

50

60

70

80

90

100

Re

lea

se

aft

er

12

Hr.

(%

)





Establishing Design Space & Control Strategy

Figure 10: FDS Graph

Fraction of Design Space Graph shows relationship between design space volume & prediction

error quantity indicating fraction (percentage) prediction error or lower. Good design will have

flatter & lower curve than poor design as shown in figure 29. Flatter means overall prediction

error will be constant. Lower means overall prediction error will be smaller. FDS should be at

least 0.8 or 80% of exploration, & 100% for robustness testing. In extraction of mucilage FDS

was 0.93 or 93%, which indicating robust Standard error of prediction relates to prediction

interval around predicted response at given pair of factor levels.

Validation:

From polynomial equations generated in response using intensive grid & integrated search was

done over experimental field & one formulation was selected. Predicted & experimental values

of selected batch responses & percentage error indicate high prognostic ability using RSM

optimization. Percentage error varied between 0.6 & 1.9 from contrast of experimental responses

with those of anticipated responses indicating validity of applied model.

Check point analysis of Validation Batches

Two extra designs, check point formulation batches RPGFT10 & RPGFT11 were developed &

predicted & experimental values of dependent variables were compared using pooled t - test at

95% confidence interval, 4- degree of freedom & p < 0.05 of two batches RPGFT10 &

RPGFT11 thus starting validity of created model.

Design-Expert® Software

Min Std Error Mean: 0.333Avg Std Error Mean: 0.471Max Std Error Mean: 0.667Cuboidalradius = 1Points = 50000t(0.05/2,6) = 2.44691d = 1.4207, s = 1FDS = 0.93Std Error Mean = 0.581

0.00 0.20 0.40 0.60 0.80 1.00

0.000

0.200

0.400

0.600

0.800

1.000

FDS Graph

Fraction of Design Space

Std Er

ror M

ean



Table 6: Validation Batches (RPGFT1 & RPGFT2): Predicted Response

Batch

No

Carbop

ol (X1)

HPMC

(X2)

Buoyan

cy -%

(Y1)

Total

floatin

g time

(Y2)

Release

after 12

Hr.%

(Y3)

RPGFT

1015.696 11.117 86.422 18.54 72.53

RPGFT

1115.50 13.90 86.126 18.55 72.76

Table 7: Validation Batches (RPGFT10 & RPGFT11): Actual Response

Batch NoCarbop

ol (X1)

HPMC

(X2)

Buoyan

cy -%

(Y1)

Total

floating

time

(Y2)

Release

after 12

Hr.%

(Y3)

RPGFT1

015.696 11.117 85.412 17.84 73.54

RPGFT1

115.50 13.90 84.361 17.18 71.47

% Cumulative Drug Release Profile:

Figure 11: % Cumulative Drug Release Profile of AT Microsponge (RPGFT10-RPGFT11)

-10

0

10

20

30

40

50

60

70

80

0 2 4 6 8 10 12 14

CUMULATIVE DRUG RELEASE

RPGFT10 RPGFT11



Selection of Optimized Formulation

RPGFT10 was found & selected validated optimized Batch with having as per its evaluation

report.

Preparation & Characterization of Repaglinide Floating Tablets

Table 8: Formulation Design of Tablet

Ingredient (mg) TMBT1 TMBT2

Repaglinide 5 5

HPMC 14 16

Carbopol 18 18

Sodium bicarbonate 50 50

Citric Acid 10 10

MCC 60 60

Mg. Stearate 3 3

Talc 5 5

Lactose 35 33

Total 200 200

Table 9: Pre-compression Evaluation of powder blend

Batch

Code

Pre-compression Evaluation of powder blend

Bulk density

(gm/cm3)

(n=3)

Tapped Density

(gm/cm3)

(n=3)

Carr’s

Index (%)

Hausner’s

Ratio

Angle of

Repose (θ)

TMBT1 0.526±0.010 0.563±0.005 6.57 1.07 21º

TMBT2 0.539±0.005 0.617±0.012 12.64 1.14 20º

The bulk density & tapped density of lubricated blends was found to be range of 0.526±0.010 to

0.539±0.005 gm/cm3 & 0.563±0.005 to 0.617±0.012 gm/cm3. Carr’s index was found to be range

of 6.57 to 12.64% showed good compressibility. Hausner’s Ratio was found to be range of 1.07

to 1.14 & angle of repose was found to be range of 20º to 21º showing good flow property.

Post-compression evaluation parameter of tablets:



Hardness: The hardness of tablets of all batches was found to be in range of 4.67 ± 0.2 to 4.78 ±

0.1 kg/cm2. The thickness of tablets of all batches was found to be in range of 3.44±0.15 to

3.49±0.15 mm. Friability of tablets measured by using Roche friability apparatus. The friability

of all tablets of all batches was come within official limit of not more than 1%. Weight variation

study was performed using analytical weight balance. All batches pass weight variation test as %

deviations are within range of ± 7.5 %.

Table 10: In-vitro Floating Duration & Floating Lag Time

Formulation

Floating Lag Time

(Sec)

(mean ± SD) (n=3)

Floating Duration

(hr)

(mean ± SD) (n=3)

TMBT1 28±3 >12

TMBT2 33±2 >12

After 15 sec After 20 sec

Figure 12: Initial stage

Figure 13: Swelling Index of tablet

0100200300400500

0 5 10 15 20 25 30

% S

wel

ling

Inde

x

Time (hrs.)

% Swelling Index of Floating tablet

TMBT1 TMBT2



Figure 14: Swelling Index of tablet

Evaluation data for % drug release of formulated tablets & comparison with marketed

conventional Formulation

Figure 15: Drug Release Profile

Release Kinetic

The results indicate that there was no evident of change in physical appearance & % drug content

of formulations after subjecting them to stability studies. Optimized Repaglinide (RPGFT10)

loaded tablet formulation was chosen for stability studies from each concentration & each

polymer based on their release characteristics & no significant changes when compared to initial

formulations.

-100

102030405060708090

1 2 3 4 5 6 7 8 9

% C

DR

time (hrs.)

% Drug Release comparission with marketed Formulation

Time (hrs.)

TMBT1

TMBT2

Marketed ConventionalFormulation



CONCLUSION

The floating tablets were evaluated for their physico-chemical properties, in-vitro release and

stability studies. The order of Swelling index was found to be Carbopol 934P > sodium alginate

> HPMC K100M > HPMC K15M > HPMC K4M. Sodium bicarbonate at the concentration of

14 %w/w was found to be ideal in achieving the buoyancy. The buoyancy lag time was found to

be less than 1 minute. In all formulations prepared, to be released 80.12% of drug in a period of

12 hrs. Tablets followed diffusion controlled first order kinetics.

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AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL … · Repaglinide requires frequent dosing before meals due to short ... Effect of different variables was checked by ... The harness of