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International Journal of Universal Pharmacy and Bio Sciences 3(3): May-June 2014

INTERNATIONAL JOURNAL OF UNIVERSAL

PHARMACY AND BIO SCIENCES IMPACT FACTOR 1.89***

ICV 5.13*** Pharmaceutical Sciences RESEARCH ARTICLE……!!!

FORMULATION AND IN-VITRO EVALUATION OF SERTRALINE HCl

FAST DISSOLVING TABLET

Divyang I Patel, Jaydeep M Rathod, DR. K.R Patel, DR. M.R Patel

B. M. Shah College of Pharmaceutical education and research Modasa.

KEYWORDS:

HPβ-CD, Disintegration

time, wetting time,

Indion-414, 32 factorial

design, In-Vitro drug

release.

For Correspondence:

Divyang I Patel *

Address:

B. M. Shah College of

Pharmaceutical

education and research

Modasa.

Email:

[email protected]

ABSTRACT

Sertraline HCl is poorly water soluble drug. It should be come into

the BCS Class II drug. It undergoes extensive hepatic metabolism.

Hence oral Bioavailability of Sertraline HCl is less (46%). To

develop novel dosage form fast dissolving tablet of Sertraline HCl

by solid dispersion techniques for enhancing solubility and prevent

hepatic metabolism. The fast dissolving tablet of Sertraline HCl

was prepared by solid dispersion using solvent evaporation

techniques. Solid dispersion prepared with carrier HPβ-CD. So

prepare solid dispersion was further used in tablet. Tablet prepared

by direct compression method using different superdisintegrants

(SSG, Crosprovidone, Indion-414) in a different concentration (1%

and 2%). The formulation was optimized by 32 full factorial

designs by selecting independent variable. Different Ratio of drug

to carriers (Sertraline: HPβ-CD) selected as factor X1 and different

concentration of super disintegrants (Indion-414) selected as X2.

The prepared formulations were evaluated for various evaluations.

Statistical analyses as well as kinetic studies are performed.



INTRODUCTION:

Potential bioavailability problem are prevalent with extremely hydrophobic drug (aqueous solubility

less than 0.1mg/ml at 37 ºC) due to erratic or incomplete absorption. The solid dispersion approach

has been widely and successfully applied to improve the solubility, dissolution rate and consequently

the bioavailability of Poorly water soluble drug. Number of drug has been shown to improve their

dissolution character when converted to solid dispersion. Because of Poorly solubility of Sertraline

HCl may pose dissolution related problem. In context of above principle a strong need is felt to

developed a solid unit dosage form that deliver Sertraline HCl in a form that dissolve very rapidly to

reduce its onset time to produce quick pharmacological effect. Thus an attempt is made in the

present investigation to improve the dissolution of Sertraline HCl through the formulation of solid

dispersion using water soluble carrier by melt solvent and solvent evaporation method and co

convert the optimized solid dispersion in fast dissolving tablet formulation.

Moreover, Sertraline HCL passes from first pass metabolism about 56% of a dose being metabolised

before reaching the systemic circulation. Also, Sertraline HCl has large value of Tmax about 6 hours.

So from all the discussion, the ideal delivery route for Sertraline HCL is one by which we can

modify its Tmax and Cmax to a better side. With this we can achieve two targets with one arrow.

First, we can increase bioavailability (more Cmax) as there is no first pass metabolism in fast

dissolving route. At salivary pH less drug ionized compare to stomach so rapid absorption is there

(less Tmax). Sertraline HCl is an antidepressant drug which exhibit 44%of oral bioavailability

because of extensive firstpass metabolism and low solubility. This one is the major problem.

Although oral administration is the most popular route many patient find in difficulties with solid

dosage swallow solid unit dosage form and do not take their medication as prescribed .it is estimated

that 50% of the population is affected by the problem of difficulties in swallowing which result in

high incidence of patient compliance and ineffective therapy.

MATERIAL AND METHOD:

Sertraline Hydrochloride was Supplied by cadila Ahemedabad, Hydroxy propyl beta cyclodextrin

supplied by Triveni intercom Pvt. Ltd. Indion-414 Supplied by Corel pharma Ahemedabad.

PREPARATION OF SOLID DISPERSION:

Selection of carrier carried out in preliminary work on the basis of data collect from literature

review. Following carrier has been selected.

1. Hydroxyl propyl beta cyclodextrin (HPβCD)

Drug and carrier (Hydroxyl Propyl beta cyclodextrin, was prepared in Ratio of 1:1, 1:2, 1:3 by

solvent evaporation method.



In this method accurately weight barrier was carefully transferred in to 10 ml Ethanol. Than

accurately quantities of drug was added and allow dissolving. The resulting solvent was completely

evaporated on a water bath For 45 minutes. The resultant mass was than Crushed, pulverized and

sifted through sieve no #80.The entire collected solid dispersion store in well closed container.

EVALUATION OF SOLID DISPERSION:

A. Differential Scanning calorimetry13

Differential scanning calorimetric performed by differential scanning calorimeter to obtain Suitable

thermograms. The accurately weighed sample was placed in an aluminium crucible and empty pan

was used as references. The experiment was perform under a nitrogen flow at a scanning rate 30

ºC/min in a range of 50-350 ºC.

B. Drug Content10

Powder equivalent to 25 mg of Sertraline HCl was weighed and the weighed amount was dissolved

in 25 ml methanol in different volumetric flask to obtain a stock solution of 1000 µg/ml. 1 ml was

pipette out and diluted with methanol to 10 ml in each case, so as to get 100 µg/ml solutions. The

absorbance was noted down after filtering off the solution at 273 nm. The average weighs of drug

present in each solid dispersion was calculated and compared with claimed amount

C. In vitro dissolution study of prepared solid dispersion10

In vitro dissolution study of prepared complex was conducted using USP dissolution apparatus II at

50 rpm, using 900 ml phosphate buffer pH 6.8 as a dissolution media Maintaining at 37± 0.5 ºC

Accurately Quantity of prepared solid dispersion equivalent to 25 mg of drug was taken. 5 ml

sample were withdrawn at time interval of 2, 4, 6, 8, 10, 12 minutes and filtered through a 45µm

filter paper and assayed at 273 nm using UV Visible double beam spectrophotometer. The volume of

dissolution medium adjusted by the replacing each 5 ml aliquot withdrawn with 5 ml of 6.8 pH

phosphate Fresh buffer.

Preparation of Fast Dissolving Tablet containing Solid Dispersion of Sertraline:

The amount of complex equivalent to 25 mg of drug per tablet were taken and mixed with directly

compressible diluents and superdisintegrants in mortar with help of pestle. Then finally aspartame as

sweetener and magnesium stearate as a lubricant was added. The blend was than compressed using 8

mm punch using Rimek tablet machine. The total weight of tablet maintains 150 mg.

Evaluation of Powder bend

Pre Compression Parameter

Loose Bulk Density3

Weigh accurately 5 gm of powder blend, and transferred in 100 ml graduated cylinder.

Carefully level the powder blend without compacting, and read the unsettled apparent volume (V0).



Calculate the apparent bulk density in gm/ml by the following formula:

Bulk Density = Mass/ apparent volume

Tapped Bulk Density35

Weigh accurately 5 gm of powder blend, and transferred in 100 ml graduated cylinder. Then

mechanically tap the cylinder containing the sample by raising the cylinder and allowing it to drop

under its own weight using mechanically tapped density tester that provides a fixed drop of 14 ± 2

mm at a nominal rate of 300 drops per minute. Tap the cylinder for 500 times initially and measure

the tapped volume (V1) to the nearest graduated units, repeat the tapping an additional 750 times and

measure the tapped volume (V2) to the nearest graduated units. If the difference between the two

volumes is less than 2% then final the volume (V2). Calculate the tapped bulk density in gm/ml by

the following formula:

Tapped Density = Mass/ tapped volume

Carr’s Index3

The Compressibility Index of the powder blend was determined by Carr’s compressibility index. It is

a simple test to evaluate the Bulk Density and Tapped Density of a powder blend and the rate at

which it packed down. The formula for Carr’s Index is as below:

Carr’s Index = Tapped Density-Bulk Density×100/ Tapped Density

Hausner’s Ratio2

The Hausner’s ratio is a number that is correlated to the flow ability of a powder blend material.

Hausner’s Ratio = Tapped density / Bulk density

Effect of Carr’s Index and Hausner’s Ratio on flow properties

Carr’s Index Flow Character Hausner’s Ratio

≤ 10 Excellent 1.00-1.11

11-15 Good 1.12-1.18

16-20 Fair 1.19-1.25

21-25 Passable 1.26-1.34

26-31 Poor 1.35-1.45

32-37 Very Poor 1.46-1.59

>38 Very, very poor >1.60

Angle of Repose2

The angle of repose of powder blend powder was determined by the funnel method. The powder

blend was taken in the funnel. The height of the funnel was adjusted in such a way the tip of the

funnel just touched the apex of the powder blend. The powder blend was allowed to flow through the

funnel freely on to the surface. The diameter of the powder blend cone was measured and angle of

repose was calculated using the following Equation.

Angle of Repose (θ) = tan-1

(h/r)

Where, h = Height of the powder blend cone

r = Radius of the powder blend cone



Post compression parameter

Thickness2

Tablet thickness is an important characteristic in reproducing appearance and also in counting by

using filling equipment. Some filling equipment utilizes the uniform thickness of the tablets as a

counting mechanism. Ten tablets were taken and their thickness was recorded using micrometer.

Hardness4

Hardness of tablet is defined as the force applied across the diameter of the tablet in the order to

break the tablet. The resistance of the tablet to chipping, abrasion or breakage under condition of

storage transformation and handling before usage depends on its hardness. Hardness of the tablet of

each formulation was determined using Monsato Hardness tester.

Friability (F)5 :

Friability of the tablet determined using Roche friabilator. This device subjects the tablet to the

combined effect of abrasion and shock in a plastic chamber revolving at 25 rpm and dropping a

tablet at I height of 6 inches in each revolution. Pre weighted sample of tablets was placed in the

friabilator and were subjected to the 100 revolutions. Tablets were dusted using a soft muslin cloth

and reweighed. The friability (F) is given by the formula.

W initial – W final

F = -------------------------- X 100

W initial

Uniformity of weight27

As per I.P. procedure for uniformity of weight was followed, twenty tablets were taken and their

weight was determined individually and collectively on a digital

Weighing balance. The average weight of one tablet was determined from the collective weight. The

weight variation test would be a satisfactory method of determining the drug content uniformity.

Uniformity of weight

Average weight of

tablets (mg)

Maximum Percentage

different allowed

130 or less 10

130-324 7.5

More than 324 5

Wetting time1:

This method was applied to measure tablet wetting time. A piece of tissue paper twice was placed in

small Petridish ( i.d=6.5 cm) containing 6 ml of water, a tablet was put on the paper, and the time

for complete wetting was measured. Three trial for each batch were performed and standard

deviation was also determined.



In-vitro disintegration time4:

The process of breakdown of tablet into smaller particle is called as disintegration the in vitro

disintegration time of tablet was determined using disintegration apparatus as per I.P specification.

Place one tablet in each of the 6 tubes of the basket . Add a disc to each tube and run the apparatus

using pH 6.8 (simulated fluida0 maintain at 37º ± 2 ºC as the immersion liquid. The assembly should

be raised and lowered between 28 cycles per minute in the pH6.8 maintained at 37º ± 2 ºC. The time

in second taken for complete disintegration of tablet with no palpable mass remaining in the

apparatus was measured and recorded.

In vitro Dissolution Study of tablet: In vitro dissolution study of prepared complex containing

tablet was conducted using USP dissolution apparatus II at 50 rpm, using 900 ml phosphate buffer

pH 6.8 as a dissolution media Maintaining at 37± 0.5 ºC Accurately Quantity of prepared solid

dispersion equivalent to 25 mg of drug was taken. 5 ml sample were withdrawn at time interval of

2, 4, 6, 8, 10, 12 minutes and filtered through a 45µm filter paper and assayed at 273 nm using UV

Visible double beam spectrophotometer. The volume of dissolution medium adjusted by the

replacing each 5 ml aliquot withdrawn with 5 ml of 6.8 ph phosphate fresh buffer.

Statistical analysis

The statistical analysis of the factorial design batches was performed by multiple regression analysis

using Microsoft Excel. Data obtained from all formulations were analyzed using statistica software

and used to generate the study design and the response surface plots. Polynomial models were

generated for all the response variables using Microsoft Excel. In addition analysis of variance

(ANOVA) was used to identify significant effects of factors on response regression coefficients. The

F value and p values were also calculated using Microsoft Excel. The relationship between the

dependent and independent variables was further elucidated using response surface plots

The drug released data of all batches were fitted with desired kinetic model such as Zero order

kinetic, First order kinetic, Higuchi model and Korsemeyer peppas model to ascertain the drug

release. The Zero order and First order drug release. The Zero order and First order drug release

explain the drug release depend on drug concentration or not. The Korsemeyer peppas model

described the method of drug release and Higuchi model described the diffusional drug release.

Zero order = Q1 = Q0 + K0t

First order = Qt = Q0e-K1t

Higuchi model = m= (100-q) ×t1/2

Hixon Crowell Model = W01/3

– Wt1/3

= kt

Korsemeyer peppas model = Mt/Mα = K × t n



Where Q1 is the amount of drug dissolved in time t, Q0 is the initial amount of drug in the solution,

Qt is the amount of drug dissolved in time t, W0 is initial amount of drug in dosage form, Wt is

remaining amount of drug in dosage form at time t, Mt/Mα is the fraction of drug release at time t

and n is diffusion exponent. K0, K1, and k refer to the rate constant.

Accelerated stability study

The purpose of stability testing is to provide evidence on how the quality of drug substance or drug

product varies with time under the influence of a variety of environmental factors such as

temperature, humidity, and light, and to establish a re-test for the drug substance or a shelf life for

the drug product and recommended storage condition. The storage condition used for stability

studies were accelerated condition (400C ± 2

0C / 75 % ± 5% RH). Stability study was carried out for

the optimized formulations. Tablets of optimized formulation were striped packed and

kept in humidity chamber on above mention temperature.

Result and discussion:

Fast dissolving tablet of Sertraline HCl were prepared by solid dispersion using solvent evaporation

technique. Solid dispersion was prepared with HPβ-CD and PVP K30 in different ratios. Solid

dispersion with HPβ-CD giving promising results. It shows highest solubility in a ratio (1:3)

compare to other carrier (PVP K30) and characterized by FTIR which indicate the HPβ-CD

compatible with Sertraline HCl. So prepared solid dispersion with HPβ-CD in (1:3) ratio was further

use in preparation of fast dissolving tablet. From the DSC study of pure drug Sharp endothermic

peak at 242.05º c it correspond to its melting point and it’s indicate its purity and crystallinity. DSC

of Solid dispersion shows that decreased thermal features of the Sertraline also indicate that it

penetrate into HPβ-CD cavity replacing the water molecule. Also length of peak decreased and

width was increase it indicates amorphous precipitation of drug. Which indicate solubility is increase

by solid dispersion. Tablet prepared by direct compression method using three super disintegrants

like (Indion-414, crosprovidone, sodium starch glycolate) in different concentration 1% and 2% in

preliminary screening of tablet. Among the all formulation, Formulation containing Indion-414 as

superdisintegrants in 2% is fulfilling all the parameter satisfactory. It shown excellent In-vitro

disintegration time and drug release compared to all other super disintegrants. The relative efficiency

of these superdisintegrants to improve the disintegration and dissolution rate of tablet was in order to

Indion-414 > Crosprovidone > Sodium starch glycolate.

For Further study Indion -414 was used in different concentration like (2, 3 or 4%) with different

drug to HPβ-CD ratios of solid dispersion (1:2.5, 1:3, 1;3.5) . The concentration of Indion-414

increase 2 to 3% that increase drug release & decrease the disintegration time but further



concentration of Indion-414 is increase from 3 to 4% it shows slightly decrease in drug release with

increase disintegration time. This could be due to remarkable swelling of Indion 414.

Table 1: Composition of Preliminary batches of tablet

INGREDIENTS

FORMULATION BATCH CODE

F1 F2 F3 F4 F5 F6

Soliddispersion(1:3)

Equivalent to 25 mg of

Sertraline HCl

100

100 100 100 100 100

MCC 21.50 20 21.50 20 21.50 20

Mannitol 20 20 20 20 20 20

Indion- 414 1% 2% - - - -

Crosprovidone - - 1% 2% - -

Sodium starch glycolate - - - - 1% 2%

Aspartame 4 4 4 4 4 4

Mg.stearate 1.5 1.5 1.5 1.5 1.5 1.5

Talc 1.5 1.5 1.5 1.5 1.5 1.5

Total weight (mg) 150 150 150 150 150 150

Table2: Drug content Studies of Fast dissolving tablet of HPβ-CD Solid Dispersion

Different Ratio Of Drug:

Carrier (Sertraline: HPβ-CD)

Result

(%)

1:1 95.58

1:2 97.38

1:3 99.34

Table 3: Result of pre compression parameter of tablet (F1-F6)

Batch

code

Bulk

density

Tapped

density

Hausner’s

Ratio

Carr’s

Index

Angle

of repose

F1 0.384 0.438 1.14 12.32 27.82

F2 0.39 0.450 1.15 13.33 27.75

F3 0.37 0.413 1.11 10.41 29.42

F4 0.37 0.416 1.12 11.05 29.57

F5 0.36 0.413 1.14 12.34 28.73

F6 0.35 0.396 1.13 11.61 29.93



Table 4: Result of post compression parameter of tablet (F1-F6)

Batch

code

Hardness*

Kg/cm2

Weight

Variation

n=10

Friability

(%)

n=10

Drug*

content

( %)

Disintegration

*

Time (sec)

F1 3.3±0.14 140.4±0.028 0.86±0.53 97.20±0.71 56±1.141

F2 3.3±0.14 145.6±0.042 0.89±0.60 99.36±0.36 42±1.20

F3 3.2±0.060 142.4±0.038 0.91±0.66 98.12±0.42 90±1.29

F4 3.5±0.61 147.3±0.070 0.84±0.24 99.15±0.24 72±2.12

F5 3.4±0.141 139.1±0.014 0.82±0.14 97.20±0.29 110±2.12

F6 3.5±0.141 138.2±0.021 0.80±0.32 98.41±0.41 82±1.14

*n=3, ±S.D

Table 5: 32 full factorial design

32 full factorial design

Independent variable Dependent veriable

X1 Drug : carrier ratio

(Drug: HPβ-CD)

X2 Conc. of Super

disintegrants

Response Y

Levels

-1 1:2.5

Levels

-1 2% Drug release at 4

minutes

Wetting time

Disintegration time

0 1:3 0 3%

+1 1:3.5 +1 4%

Table 5: Formulation of Factorial Batches

FORMU.

INGREDIENTS

FORMULATION BATCH CODE

D1 D2 D3 D4 D5 D6 D7 D8 D9

Solid dispersion eq. to

25mg Sertraline HCl

87.5 100 112.5 87.5 100 112.5 87.5 100 112.5

Indion 414 3 3 3 4.5 4.5 4.5 6.0 6.0 6.0

MCC 32.5 20.0 7.5 31.0 18.5 6.0 29.5 17.0 4.5

Mannitol 20 20 20 20 20 20 20 20 20

Aspartame 4 4 4 4 4 4 4 4 4

Mag. Stearate 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5

Talc 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5

Total weight (mg) 150 150 150 150 150 150 150 150 150



Table 6: Pre compression parameter of factorial Batches (D1-D9)

Batch

Code.

Bulk

density

Tapped

density

Hausner’s

Ratio

Carr’s

Index

Angle

of repose

D1 0.384 0.440 1.14 12.72 26.82

D2 0.392 0.450 1.14 12.88 28.10

D3 0.383 0.445 1.16 13.93 27.36

D4 0.378 0.429 1.13 11.88 29.81

D5 0.398 0.465 1.16 14.40 26.90

D6 0.380 0.431 1.13 11.83 28.43

D7 0.378 0.444 1.17 14.86 27.11

D8 0.392 0.452 1.15 13.27 28.99

D9 0.397 0.449 1.13 11.58 27.13

Table 7: Result of post compression parameter of Factorial Batches

Form.

Code

Hardness

Kg/cm2

Weight

variation

Thickness

(mm)

Friability

(% )

D1 3.3±0.14 140.4±0.038 2.92±0.05 0.87±0.53

D2 3.4±0.21 142.6±0.028 2.85±0.06 0.84±0.36

D3 3.5±0.141 146.4±0.21 2.85±0.01 0.86±0.14

D4 3.2±0.070 147.3±0.19 2.95±0.01 0.92±0.24

D5 3.4±0.141 139.1±0.042 2.84±0.09 0.82±0.23

D6 3.3±0.142 147.2±0.070 2.93±0.07 0.85±0.52

D7 3.5±0.141 145.6±0.021 2.81±0.01 0.80±0.68

D8 3.4±0.14 137.1±0.44 2.85±0.01 0.85±0.32

D9 3.3±0.21 143.1±0.047 2.93±0.04 0.84.±0.36

n=3, ±S.D

Form.

Code

Wetting

time(sec)

Drug content

(%)

Disintegration

Time (sec)

D1 38±0.38 96.20±0.36 42±2.82

D2 36±0.26 99.36±0.42 40±2.82

D3 35±0.18 97.12±0.24 39±1.41

D4 33±0.28 98.15±0.24 35±0.816

D5 31±0.92 98.20±0.41 33±2.12

D6 27±0.09 98.41±0.76 30±0.70

D7 26±0.44 97.05±0.22 37±2.12

D8 25±0.15 96.97±0.45 34±2.8

D9 23±0.72 99.36±0.28 32±2.12

n=3, ±S.D



Figure 1: DSC Spectra of Sertaline HCl

Figure 2;DSC Spectra of solid dispersion of Sertraline +HPβ-CD

Figure 3: FTIR Spectra of Sertraline hydrochloride

Figure 4: FTIR Spectra solid dispersion of drug and HPβ-CD



Figure 5: FTIR Spectra of Sertraline HCl formulation

Figure 6: In- Vitro Drug release study of solid dispersion with HPβ-CD

Figure7: Comparative In-vitro drug release Study of F1-F6 preliminary batches of tablet

0

20

40

60

80

100

120

0 5 10 15 20

pure drug

1:1(HPβ-CD:drug)

1:2(HPβ-CD:drug)

1:3(HPβ-CD:drug)

C

P

R

Time (min)

0

20

40

60

80

100

120

0 5 10 15 20Time (min)

f1

f2

f3

f4

f5

f6

CP



Figure 8: Cumulative percentage drug release of batches(D1-D3)



0

20

40

60

80

100

120

0 2 4 6 8 10

C

P

R

Time (min)

D1

D2

D3

0

20

40

60

80

100

120

0 2 4 6 8 10

C

P

R

Time (min)

D4

D5

D6

0

20

40

60

80

100

120

0 2 4 6 8 10

C

P

R

Time (min)

D7

D8

D9



Results of Statistical analysis

Table 8 :Statistical analysis of dependent variable

Batch

code

Variable level Disintegration

time(sec)

Drug

release at

4 minutes

Wetting

time

(sec) X1 X2

D1 -1 -1 42 59.07 38

D2 0 -1 40 70.148 36

D3 +1 -1 39 75.188 35

D4 -1 0 35 64.12 33

D5 0 0 33 75.98 31

D6 +1 0 30 83.64 27

D7 -1 +1 37 61.76 26

D8 0 +1 34 72.44 25

D9 +1 +1 32 77.89 23

Full and reduced model for drug release at 4 minutes

FM Y=77.5316676+8.769562607(X1)+1.15(X2)-0.195(X12)-

3.23(X1)2 – 5.826 (X2)

2

RM Y = 77.53166 +8.76990566 (X1) -3.23(X1) 2-5.826 (x2)

2

Table 9: Summary of regression analysis

Drug release at 4 minutes

Response bo b1 b2 b12 b11 b22

FM 77.53 8.76 1.15 -0.195 -3.23 -5.826

P value 3.65E07 0.00491 0.106 0.772 0.033 0.0068

RM 77.53 8.76 - - -3.23 -5.826

.

Figure 11:Surface plot for drug release at 4 min



The coefficient of x1 that is , b1 bear a positive sign & coefficient of x2 that is b2 bear a positive

sign, and thus increasing ratio of drug : carrier increases the release rate of drug and x2 is a

concentration of Indion -414 thus increasing concentration of Indion increase the drug release at

certain extend.

Full and reduced model for disintegration time

FM Y = 32.5533-2.16(X1)-3(X2)-0.5(X12)+0.16(X1)2+4.66(X2)

2

RM Y = 32.55 -2.16(X1) -3 (X2) +4.66(x2)2



FM 32.55 -2.16 -3 -0.5 0.166 4.666

P value 3.49E-06 0.001773 0.000721 0.144 0.674 0.000991

RM 32.66 -2.16 -3 - - 4.66

Figure 12: surface plot for disintegration time

The coefficient of x1 that is , b1 bear a positive sign & coefficient of x2 that is b2 bear a positive

sign, and thus increasing ratio of drug : carrier increases the release rate of drug and x2 is a

concentration of Indion -414 thus increasing concentration of Indion increase the drug release at

certain extend.

Full and reduced model for wetting time

FM Y = 32.5533-2.16(X1)-3(X2)-0.5(X12)+0.16(X1)2+4.66(X2)

2

RM Y = 32.55 -2.16(X1) -3 (X2) +4.66(x2)2


Wetting time (sec)


FM 30.55 -2 -5.83 -5.6E-17 0.333 0.166

P value 4.51E-06 0.0222 0.00104 1 0.702 0.884

RM 30.34 -2 -5.83 - - -



Figure 13; surface plot for wetting time

The coefficient of x1 that is , b1 bear a negative sign & coefficient of x2 that is b2 also bear a

negative sign, and thus increasing ratio of drug: carrier decrease the wetting time of tablet and x2 is

a concentration of Indion -414 thus increasing concentration of Indion decreases the wetting time.

Table 12: KINETIC TREATMENT OF DISSOLUTION DATA

Batch Code D1 D2 D3 D4 D5 D6 D7 D8 D9

Zero order

R2 0.982 0.971 0.989 0.994 0.976 0.980 0.993 0.960 0.997

B 6.913 7.668 8.549 8.664 8.822 10.04 7.930 7.531 8.477

A 30.95 39.55 41.05 29.46 40.69 43.24 30.04 42.31 43.99

First order

R2 0.955 0.938 0.972 0.980 0.954 0.963 0.973 0.928 0.956

B 0.048 0.049 0.052 0.050 0.054 0.059 0.053 0.047 0.050

A 1.552 1.630 1.653 1.548 1.647 1.674 1.55 1.653 1.676

Higuchi

R2 0.995 0.993 0.997 0.993 0.994 0.993 0.995 0.988 0.995

B 29.70 30.58 31.84 33.73 33.19 35.42 32.51 30.20 31.84

A 2.588 11.72 13.91 -0.29 12.07 14.44 -0.04 4.638 16.57

Hixon Crowell

R2 -0.983 -0.971 -0.981 -0.994 -0.976 -0.980 -0.993 0.960 -0.997

B -2.29 -2.55 -2.84 -2.88 -2.94 -3.34 -2.59 -2.48 -2.82

A 22.95 20.14 19.65 23.51 19.76 18.91 23.31 19.22 18.66

Korsmeyer and Peppas

R2 0.996 0.996 0.995 0.992 0.996 0.994 0.993 0.994 0.996

N 0.477 0.422 0.390 0.479 0.417 0.398 0.484 0.405 0.384

A -0.49 -0.38 -0.34 -0.461 -0.35 -0.30 -0.47 -0.36 -0.323

B = slope, A= intercept n= Release Exponential

R2= Square of correlation coefficient,



Table 13: Evaluation Result of stability study

Parameter Weight

variation

(mg)

Disintegration

Time(sec)

Drug

content

(%)

Wetting

time

(sec)

Initial 147.24 30 98.41 27

After 1 month 143.92 33 97.20 30

Figure 14: Comparative dissolution profile of D6 batch before and after stability

Conclusion:

The concentration of Indion-414 increase 2 to 3% that increase drug release & decrease the

disintegration time but further concentration of Indion-414 is increase from 3 to 4% it shows slightly

decrease in drug release with increase disintegration time. This could be due to remarkable swelling

of Indion 414. So finally it concludes that optimized concentration for Indion 414 is 3%. All the

batches were evaluated for pre compression and post compression parameter shown within the limit.

Among the all formulation tablet prepared with Indion-414 as superdisintegrants gives excellent

drug release with less disintegration and wetting time compared to other superdisintegrants. So from

the release study of factorial batches D6 batch containing 3% indion-414 with drug to HPβ-CD ratio

(1:3.5) of solid dispersion shows faster drug release with less disintegration time compared to other

batches. So D6 batch is optimized batch. Optimized batch D6 shown that 98.83 % drug release at the

end of 6th minutes with 30 sec disintegration time and 27 sec wetting time. It also had desired

release kinetics. It also found to be stable for the period of 1 month. Overall drug release followed

zero order with Fickkian diffusion. The stability was conducted for formulation F6 at 40º C / 75%

RH for 30 days various parameter like drug content, weight variation, wetting time, disintegration

time, In vitro release. Not much variation changed was observed in any parameter study period. Best

selected formulation (D6) found to be Stable on the basis of Similarity and Dissimilarity (f1=1.14,

f2=97.69) factor. So prepared fast dissolving tablet of Sertraline HCl enhance the absorption and

increase the bioavailability of Sertraline hydrochloride.

0

20

40

60

80

100

120

0 2 4 6 8

% cpr D6 batch (initial)

% cpr of D6 batch after stability study

CpR

Time (min)



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