Result and Discussion 6

8/19/2019 Result and Discussion 6

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Results

RESULT AND DISCUSSION

3.3 EVALUATION AND OPTIMIZATION OF FLOATING

TABLETS

3.3.1. Physical paa!"#"s

3.3.1.A Si$" a%& Shap": - The shape tablets were evaluated visually and the

size particularly thickness was measured with the help of screw gauge.

3.3.1.B '"i(h# Vaia#i)%: - The individual of 20 tabletss from each batch

were weighed accurately to determine the weight variations. As per the !" all the

tablets must within the the range of # $. The sample mean and standard deviation of

each batch of tablets were determined %table&.

3.3.1.C *a&%"ss: - The hardness individual '0 tablets from each batch were

determined with the help of "fizer hardness tester and the sample mean and standard

deviation were calculated for each batch %table&.

3.3.1.D Fia+ili#y, - (t was determined with )oche friabilator apparatus

%*icon+ (ndia&. ,ollowing formula was used to determination of friability:

,riability %(nitial wt - ,inal wt (nitial wt & / '00

Ta+l" 3., A/"a(" ha&%"ss a%& 0ia+ili#y

S.N). F)!la#i)% c)&" A/"a(" ha&%"ss 2(4c! 5 A/"a(" 0ia+ili#y 265

'. "' 2.$#0.$2 0.1# 0.0'$

2. "2 2.34#0.2' 0.14#0.002

5. "5 '.6#0.25 0.1#0.0'

3. "3 5.0'#0.3$ 0.10#0.025

$. "$ 5.5#0.'4 0.10#0.025

6. "6 5.'4#0.2$ 0.4$#0.0''

4. "4 2.15#0.52 0.1'#0.03

1. "* 5.#0.26 0.65#0.04

. * 3.2#0.3 0.$'#0.014'0. "' 2.'5#0.56 0.'#0.0'6

''. "2 2.26#0.'' 0.1#0.064

'2. "5 '.1#0.2 0.1#0.035

'5. "3 2.45#0.3 0.12#0.0'4

'3. "$ 5.0'#0.'' 0.12#0.0'

'$. "6 5.25#0.'$ 0.41#0.04$

'6. "4 2.45#0.32 0.15#0.0$'

'4. "* 3.'6#0.'$ 0.6$#0.063

'1. "7' 2.14#0.5' 0.41#0.0$5

'. "72 2.15#0.55 0.4'#0.01

20. "7' 5.25#0.2$ 0.15#0.05'

2'. "72 2.#0.2 0.4$#0.0'

Dept. of Pharmaceutical Sciences S.S.I.T.M.65


2/65

Results

8ean # !+ n 5

Ta+l" 3.3, A/"a(" 7"i(h# a%& #hic%"ss

S.N). F)!la#i)% C)&" A/"a(" '"i(h# 2!(5

A/"a(" #hic%"ss 2!!5

'. "' 32.55#'.$5 $.$3# 0.452. "2 6'0.55#'.$5 $.64#0.'

5. "5 452#2.6$ 6.62#0.''

3. "3 45'.5#2.52 6.$3#0.'

$. "$ 412.36#'.52 6.$#0.'

6. "6 405.44#'.' 6.35#0.26

4. "4 463.44#2.5$ 6.$#0.'5

1. "*

455.35#2.36

6.31#0.54

. * 45'.14#'.51

6.3'#0.34

'0. "' 33#'.45$.$6#0.45

''. "2 6''#'.5

0.$.42#0.5'

'2. "5 452.6#5.'5

6.65#0.'$

'5. "3 42.'4#2.3'

6.$4#0.'5

'3. "$ 41'.14#'.5$

6.$'#0.'4

'$. "6 405.'#'.54

6.63#0.53

'6. "4 465.5#2.0$

6.6'#0.2'

'4. "* 455.'5#'.$

6.$#0.'1

'1. "7' 462.1#2.36

6.4#0.45

'. "72 42.''#'.33

6.'#0.63

20. "7' 465.05#'.$5

6.13#0.3

2'. "72 42.'#'.'$6.4#0.'3

8ean # !+ n 5

3.3.1.D Fl)a#i%( la( Ti!" a%& &a#i)% )0 0l)a#i%(, - The buoyancy lag time and

uration of floating were determined in the !" issolution apparatus (( in an acidic

environment %0.'9 *7+ 00 ml+ $0 )"8&. The time interval between introduction of

the tablets in to the dissolution medium and its buoyancy to the top of the dissolution

medium was taken as buoyancy lag time and duration of buoyancy was observed



3/65

Results

visually. The sample mean and standard deviation of each batch of tablets were

determined %n 5&.

3.3.1.E D"%si#y, - The apparent densities of the tablets were calculated from their

volumes and masses in triplicate. ;oth parameters were determined in 0.' 9 *7

after floating the tablets. The volumes < of the spherical tablets were calculated from

their radii %determine with a micrometer gauge i.e. screw gauge& using the

mathematical e=uation for a circle %3 5 >r 5&. The sample mean and standard deviation

of each batch of tablets were determined %n 5&.

3.3.1.F Di!"%si)%al S#a+ili#y, - The dimensional stability of formulation was studiedusing !" issolution Apparatus ((. The dissolution medium was 0.'9 *7 and the

volume being 00 ml. The temperature was maintained at 54 # $ 07. The rotation

speed was $0 rpm. The dimensional stability of the theophylline floating tablets was

observed visually. The sample mean and standard deviation of each batch of tablets

were determined %Table 5.5&.

3.3. C)%#"%# U%i0)!i#y, - The drug content of at least 6 tablets from each batch

was determined. The tablets were weighed collectively+ pulverized. The weight e=ual

to single tablet was weighted and dissolved in '00 ml of 0.'9 *7 solutions. The

drug solution was filtered. Ali=uots of filtrate was diluted suitably and analyzed

spectrophotometrically %!himadzu '400+ ?apan&at 240 nm. The sample mean and

standard deviation of each batch of tablets were determined. %Table 5.3&.

Ta+l" 3.8, Fl)a#i%( capa+ili#i"s )0 &i00""%# +a#ch"s )0 #h")phylli%" 0l)a#i%(

!a#i9 #a+l"#s

S.N). F)!la#i)%

c)&"

D"%si#y

2!(4c!35

Fl)a#i%( capa+ili#i"s

Fl)a#i%(

la( 2s"c5

Fl)a#i%(

&a#i)%2h)s5

Di!"%si)%al

s#a+ili#y

'. "' 0.4#.025 534# 1.6 ''.5 #0.2$ 9ote retain

2. "2 '.03 # 0.024 21#4.$' '4.#0.51 9ote )etain

5. "5 '.034# 0.023 '02#2.$6 @ 23 )etain

3. "3 0.41# 0.01$ 41#'.5 @ 23 )etain well

$. "$ '.02#0.0'' 4'#5 @ 23 )etain well

6. "6 '.025#0.06 1#2.$' 22 # 0.6' )etain

4. "4 0.6#0.02' 60.4#2.$2 @ 23 )etain well

1. "* 0.42#0.01$ 34.5#2.01 @ 23 )etain well

Dept. of Pharmaceutical Sciences S.S.I.T.M.6$


4/65

Results

. * 0.$$#.023 '0.5#'.$5 @ 23 )etain well

'0. "' 0.51#0.0'$ 5$$#3.$1 '2.6 # 0.$6 9ote retain

''. "2 0.$#.0$ 23#3.$1 '#.16 9ote )etain+

'2. "5 '.006#.04$ '20#2.$2 @ 23 )etain

'5. "3 0.4$#0.0'1 1$.4#$.05 @ 23 )etain well

'3. "$ 0.31#0.015 4.5#'.$5 @ 23 )etain well

'$. "6 '.022#0.026 '0$#$.2 20.2# 0.1$ )etain

'6. "4 '.005#.024 6.4#2.01 @ 23 )etain well

'4. "* 0.33#0.033 $$#' @ 23 )etain well

'1. "7' 0.6#0.0'' $$.'#'.$5 @ 23 )etain well

'. "72 0.$#0.025 3$#2 @ 23 )etain well

20. "7' 0.64#0.56 6'.$#'.52 @ 23 )etain well

2'. "72 0.$#0.25 $0#'.65 @ 23 )etain well

8ean # !+ n 5

Ta+l" 3.:, D( c)%#"%# %i0)!i#y )0 &i00""%# +a#ch"s )0 #h")phylli%" 0l)a#i%(

!a#i9 #a+l"#s

S.N). F)!la#i)%

c)&"

La+"l"&

a!)%# )0

&( 2!(5 2;5

Ac#al a!)%#

)0 &(2!(5 25

'. "' 200 '1#0.56 .0

2. "2 200 '#'.$4 .$

5. "5 200 '1.5#0.1 .'2

3. "3 200 '.$#'.$4 .4$

$. "$ 200 '1.5#'.32 .'$

6. "6 200 '1.2#2.54 .'

4. "4 200 '6.2#'.0$ 1.'

1. "* 200 '4.3#2.$4 1.4

. * 200 '4.5#'.$$ 1.6$

'0. "' 200 '1.6#0.4$ .5

''. "2 200 '4.5#0.3$ 1.6$

'2. "5 200 '4.$#2.65 1.4$

'5. "3 200 '6.2#2.04 1.'



5/65

Results

'3. "$ 200 '4.3#'.4' 1.4

'$. "6 200 '4.'4#0.1$ 1.$1

'6. "4 200 '6.64#2.'$ 1.55

'4. "* 200 '.55#0.44 .66

'1. "7' 200 '.24#'.$4 .65

'. "72 200 '.02#'.5$ .$'

20. "7' 200 '.31#'.'1 .43

2'. "72 200 '1.5$#'.2' .'4

8ean # !+ n 5

3.3.3 In-Vitro R"l"as" S#&y: -The release of theophylline from the tablets was

studied using the !" dissolution apparatus (. The dissolution medium was 0.'9 *7

and the volume being 00 ml. The temperature was maintained at 54 #0. $ 07. The

rotation speed '00 rpm. ,ive ml of ali=uot was withdrawn at a predetermine intervals

of .'+2+5+3+$+6+4+1+'0+'2+hours. The medium was replenished with five ml of fresh

0.'9 *7 at each time. The drug solution was filtered. Ali=uots of filtrate was diluted

suitably and analyzed spectrophotometrically %!himadzu '400+ ?apan& at 240 nm. B

of drug released was calculated for each interval.



6/65

Results

3.3.3, B In -Vitro R"l"as" &a#a )0 Th")phylli%" 0)! Di00""%# F)!la#i)%s

P"pa"& 7i#h D"hs Psylli! *s i% >.1N *CL

Ta+l" 3.?, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DP1 i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+. C)%c"%#a#i)% i% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"

!l : !l @>> !l

'. 0.$ 0.'$0 0.0246 0.'51 23.16 23.16 '2.35

2. ' 0.503 0.0$$ 0.210 $0.5 $0.$5 2$.26

5. 2 0.326 0.041$ 0.52 40.6' 4'.05 5$.$'

3. 5 0.$'2 0.035 0.34' 13.16 1$.64 32.13

$. 3 0.$2 0'00 0.$3$ 1.'2 .30 3.40

6. $ 0.632 0.'110 0.$' '06.3 '01.25 $3.'2

4. 6 0.63 0.'241 0.65 ''$.05 ''4.33 $1.421. 4 0.43' 0.'56$ 0.615 '22.1$ '2$.6 62.1

. 1 0.411 0.'3$' 0.4$6 '50.$ '53.55 64.'6

'0. '0 0.143 0.'6'0 0.10$ '33.16 '3.55 43.66

''. '2 0.62 0.'442 0.116 '$.3$ '63.33 12.22

Total amount of drug 200 mg+ dilution factor '0 slope 0.0$35

Fi( 3.1, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch DP1 i% >.1N *CL



7/65

Results

Ta+l" 3., In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DP i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+. C)%c"%#a#i)% i% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"

!l : !l @>> !l

'. 0.$ 0.'33 0.20 0.'0$ '1. '1.0 .3$

2. ' 0.223 0.03'5 0.206 54.'5 54.25 '1.62

5. 2 0.26 0.0$53 0.264 31.04 31.51 23.'

3. 5 0.513 0.0404 0.5$3 65.6$ 63.22 52.''

$. 3 0.332 0.01'3 0.3'0 45.26 43.' 54.0

6. $ 0.312 0.0114 0.351 4.1 10.16 30.35

4. 6 0.$'5 0.02' 0.360 12.14 13.2 32.'3

1. 4 0.$2' 0.06 0.313 14.'1 1.35 33.42

. 1 0.$36 0.03 0.34 1.$0 2.25 36.'2

'0. '0 0.662 0.'220 0.620 '0.42 ''2.$ $6.31

''. '2 0.446 0.'320 0.4'$ '21.62 '52.34 66.25


0

10

20

30

40

50

60

70

0 2 4 6 8 10 12 14

Time (hrs)

%

C u m . d r u g r e l e

a s e

Fi( 3., In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch DP i% >.1N *CL



8/65

Results

Ta+l" 3., In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DP3 i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+. C)%c"%#a#i)% i% 2!(5 C!. D(

"l"as"

6 C!.

&( "l"as"

!l : !l @>> !l

'. 0.$ 0.'02 0.0'11 0.03 '6.0 '6.0 1.32

2. ' 0.'46 0.0523 0.'62 2.'4 2.24 '3.65

5. 2 0.221 0.03$4 0.221 3'.'0 3'.$ 20.4

3. 5 0.563 0.0640 0.55$ 60.55 60.12 50.3'

$. 3 0.512 0.0405 0.5$2 65.5' 63.56 52.'1

6. $ 0.3'2 0.04$1 0.54 61.2 6.36 53.42

4. 6 0.353 0.04 0.5 4'.5 45.31 56.43

1. 4 0.36 0.0165 0.352 44.45 4.61 5.13

. 1 0.311 0.01 0.33 10.11 15.26 3'.6

'0. '0 0.$'' 0.03' 0.34' 13.'0 14.$' 35.41

''. '2 0.$$1 0.'021 0.$'3 2.3 $.4 34.1


0

10

20

30

40

50

60

0 5 10 15

Ti!" 2hs5

6

C 1 ! . & 1 ( "

l " a s "

Fi( 3.3, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch DP3 i% >.1N *CL



9/65

Results

Ta+l" 3.@, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DP8 i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% i% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.014 0.'60 0.010 '3.32 '3.32 4.2'

2. ' 0.'43 0.052 0.'60 21.15 21.2 '3.36

5. 2 0.232 0.03$ 0.225 30.'' 30.2 20.'3

3. 5 0.216 0.$26 0.265 34.3' 34.$4 25.5

$. 3 0.532 0.065 0.5'$ $0.6 $4.3' 21.4'

6. $ 0.541 0.66 0.513 62.6$ 65.6 5'.1$

4. 6 0.321 0.041 0.53 40.3 42.55 56.'6

1. 4 0.36' 0.01$ 0.323 46.3' 41.' 5.'

. 1 0.33 0.0' 0.3$$ 1'.11 13.0 32.03

'0. '0 0.$5' 0.01 0.31 11.0' 0.64 3$.53

''. '2 0.$41 0.''6 0.$52 $.10 1.$ 3.34


0

10

20

30

40

50

60

0 5 10 15

Time(hrs)

%

C u m .

d r u g r e l e a s e

Fi( 3.8: In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch DP8 i% >.1N *CL

Dept. of Pharmaceutical Sciences S.S.I.T.M.4'


10/65

Results

Ta+l" 3.1>, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DP: i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. D(

"l"as"

6 C!.

D(

"l"as"!l : !l @>> !l'. 0.$ 0.041 0.0'3 0.042 '2.5 '2.5 6.36

2. ' 0.'66 0.05' 0.'$5 24.$' 24.$1 '5.4

5. 2 0.223 0.03' 0.2'0 54.'5 54.32 '1.4'

3. 5 0.253 0.035 0.2'$ 51.4 5.22 '.6'

$. 3 0.24' 0.0$0 0.2$0 33.2 3$.$4 22.41

6. $ 0.523 0.0$ 0.21 $5.4 $3.60 24.50

4. 6 0.516 0.04' 0.5$$ 65.1 63.6 52.31

1. 4 0.322 0.044 0.51 6.3 4'.3 5$.4$

. 1 0.346 0.014 0.351 41.1 10.13 30.32

'0. '0 0.$51 0.0 0.3$ 1.'4 '..$$ 3$.41

''. '2 0.$11 0.'01 0.$3' 4.36 '00.55 $0.'4


0

10

20

30

40

50

60

0 5 10 15

Time(hrs)

%

C u m . d r u g r e l e a s

e

Fi( 3.:, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch DP: i% >.1N *CL



11/65

Results

Ta+l" 3.11, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DP? i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.04 0.0'1 0.01 '.01 '6.01 1.03

2. ' 0.'13 0.053 0.'6 50.$ 50.$ '$.2

5. 2 0.2$6 0.034 0.256 32.35 32.61 2'.53

3. 5 0.503 0.0$6 0.24 $0.5 $0.11 2$.33

$. 3 0.5$4 0.064 0.521 $.'4 $.$ 2.4

6. $ 0.546 0.06 0.531 62.64 65.44 5'.11

4. 6 0.322 0.041 0.51 6.3 4'.5 5$.6

1. 4 0.343 0.014 0.354 41.$6 10.30 30.2

. 1 0.31 0.02 0.3$ 12.$3 13.22 32.''

'0. '0 0.$54 0.0 0.33 1.0' '.3$ 3$.45

''. '2 0.605 0.''' 0.$$$ . '02.15 $'.32


0

10

20

30

40

50

60

0 0.2 0.4 0.6 0.8Time(hrs)

%

C u m .


Fi( 3.?, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch DP? i% >.1N *CL



12/65

Results

Ta+l" 3.1, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DP i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.016 0.0'4 0.015 '3.1$ '3.1$ 4.32

2. ' 0.'3 0.024 0.'54 23.66 23.43 '2.54

5. 2 0.2'6 0.05 0.' 5$.10 56.02 '1.0'

3. 5 0.266 0.031 0.23$ 33.01 33.$' 22.2$

$. 3 0.506 0.0$4 0.21$ $'.22 $'.11 2$.3

6. $ 0.554 0.62' 0.5'0 $$.1$ $6.1' 21.3'

4. 6 0.51 0.045 0.566 6$.4 64.25 55.62

1. 4 0.3'6 0.044 0.515 61.$ 40.$' 5$.2$

. 1 0.36 0.016 0.352 44.45 4.45 5.14

'0. '0 0.$02 0.02 0.362 1.40 1$.63 32.12

''. '2 0.$$ 0.'05 0.$'$ 2.6$ $.$3 34.44


0

10

20

30

40

50

60

0 0.2 0.4 0.6

Time(hrs)

%

C u m . d r u g r e l a s

e

Fi( 3., In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch DP i% >.1N *CL



13/65

Results

3.3.3.B In-Vitro R"l"as" Da#a )0 Th")phylli%" 0)! Di00""%# F)!la#i)%s

P"pa"& 7i#h *s Psylli! i% >.1N *CL

Ta+l" 3.13, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch P1 i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l

'. 0.$ 0.'45 0.052 0.'$ 21.4 21.4 '3.5

2. ' 0.55' 0.06' 0.50$ $3.16 $$.02 24.$'

5. 2 0.3$3 0.013 0.320 4$.54 4$.15 54.2

3. 5 0.$' 0.06 0.341 16.03 16.2 35.36

$. 3 0.$ 0.''0 0.$$2 .5$ '00.4' $0.5$

6. $ 0.631 0.'' 0.$4 '04.30 '0.52 $3.6$4. 6 0.615 0.'26 0.650 ''5.24 ''$.44 $4.11

1. 4 0.43' 0.'56 0.612 '22.45 '2$.44 62.11

. 1 0.442 0.'32 0.4'' '24.$ '5'.63 6$.12

'0. '0 0.1$ 0.'$1 0.4' '32.51 '36.' 45.3$

''. '2 0.32 0.'43 0.164 '$6.'5 '6'.3$ 10.42


0

10

20

30

40

50

60

70

8090

0 5 10 15Time(hrs)

%

c u m .


Fi( 3., In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch P1 i% >.1N *CL



14/65

Results

Ta+l" 3.18, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch P i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0'30 0.026 0.'5 25.2$ 25.2$ ''.65

2. ' 0.2$' 0.036 0.25 3'.46 3'.1 20.$

5. 2 0.5$2 0.06 0.55 $1.32 $1.41 2.5

3. 5 0.30 0.04$ 0.51 64.4 61.31 53.23

$. 3 0.366 0.016 0.35 44.5 41.54 5.'

6. $ 0.311 0.01 0.$3 10.12 12.52 3'.'6

4. 6 0.$02 0.02 0.36 15.20 1$.'$ 32.$4

1. 4 0.$' 0.6 0.31 16.02 11.33 33.25

. 1 0.$2$ 0.04 0.3 14.02 1.' 33.6

'0. '0 0.$4 0.'04 0.$5 $.4 .53 31.64

''. '2 0.64' 0.'23 0.62 '''.22 ''$.'' $4.$6


Fi( 3.@, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch P i% >.1N *CL



15/65

Results

Ta+l" 3.1:, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch P3 i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"

!l : !l @>> !l

'. 0.$ 0.''$ 0.02'2 0.'06 '.06 '.06 .$5

2. ' 0.'1 0.0560 0.'10 52.12 52.2 '6.36

5. 2 0.50$ 0.0$62 0.210 $0.$$ $0.13 2$.32

3. 5 0.53' 0.0621 0.5'3 $6.$2 $6.12 21.3'

$. 3 0.514 0.04'5 0.5$6 63.'3 6$.05 52.$'

6. $ 0.301 0.04$ 0.546 64.62 61.16 53.35

4. 6 0.350 0.04 0.56 4'.24 42.1 56.33

1. 4 0.3$$ 0.013 0.3' 4$.3' 44.35 51.4'

. 1 0.361 0.016 0.350 44.$4 4.6$ 5.12

'0. '0 0.3 0.02 0.360 12.'' 1$.30 32.6

''. '2 0.$50 0.01 311 14.1$ '.'4 3$.$1Total amount of drug 200 mg+ dilution factor '0 slope 0.0$35

0

10

20

30

40

50

0 5 10 15

Time(hrs)

% C u m . d r u g r e l e a s e

Fi( 3.1>, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch P3 i% >.1N *CL



16/65

Results

Ta+l" 3.1?, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch P8 i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.05 0.0'4' 0.016 '$.3' '3.3' 4.4'

2. ' 0.'15 0.0554 0.'6 50.55 50.32 '$.2'

5. 2 0.245 0.0$05 0.2$' 3$.24 3$.$2 22.46

3. 5 0.2' 0.0$30 0.261 31.25 31.43 23.54

$. 3 0.53 0.0630 0.52' $4.1$ $1.62 2.5'

6. $ 0.54' 0.0615 0.530 6'.3 62.$ 5'.2

4. 6 0.322 0.0444 0.51 6.3 4'.51 5$.6

1. 4 0.35 0.042 0.56 4'.24 45.0 56.$$

. 1 0.3$ 0.0121 0.3'3 43.$ 46.4 51.5

'0. '0 0.31' 0.010 0.335 4.42 12.43 3'.54

''. '2 0.$$' 0.'0'0 0.$0$ '.55 5.4 36.1


0

10

20

30

40

50

0 5 10 15Time(hrs)

% C u m . d r u g r e l e a s

e

Fi( 3.11, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch P8 i% >.1N *CL



17/65

Results

Ta+l" 3.1, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch P: i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.04 0.0'$6 0.045 '5.0 '5.0 6.$$

2. ' 0.'45 0.05' 0.'$ 21.64 21.4$ '3.54

5. 2 0.252 0.0324 0.2'3 51.3$ 51.61 '.53

3. 5 0.262 0.0315 0.230 35.20 35.6$ 2'.12

$. 3 0.503 0.0$$ 0.210 $0.30 $'.04 2$.$3

6. $ 0.514 0.04'5 0.5$6 63.'3 6$.'' 52.$$

4. 6 0.53 0.0426 0.560 6$.50 66.65 55.5'

1. 4 0.3'1 0.0461 0.51$ 6.21 40.6 5$.31

. 1 0.3$3 0.0136 0.3'1 4$.2$ 44.52 51.66

'0. '0 0.$03 0.052 0.340 15.34 16.5$ 35.'1

''. '2 0.$41 0.'06$ 0.$52 $.10 1.$2 3.26


0

10

20

30

40

50

60

0 5 10 15

Time(hrs)

%

C u m .


Fi(3.1, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch P: i% >.1N *CL



18/65

Results

Ta+l" 3.1, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch P? i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.'' 0.02' 0.'' '.42 '.42 .16

2. ' 0'1 0.0531 0.'4 5'.55 5'.33 '$.42

5. 2 0.216 0.0$26 0.20 34.3 33.61 25.13

3. 5 0.5'6 0.0$12 0.2 $2.51 $2.2 26.36

$. 3 0.530 0.0626 0.5' $6.5$ $4.'1 21.$

6. $ 0.541 0.066 05$ 62.63 65.41 5'.1

4. 6 0.5' 0.0420 0.56 63.1' 66.2 55.'$

1. 4 0.35$ 0.010' 03 42.' 45.$ 56.4

. 1 0.362 0.01$' 0.35 46.$4 41.12 5.3'

'0. '0 0.3$ 0.0'2 0.36 12.03 13.42 32.56

''. '2 0.$6$ 0.'03' 0.$2 5.6$ 6.4 31.5


0

10

20

30

40

50

60

0 5 10 15

Time(hrs)

%

C u m .


Fi( 3.13, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch P? i% >.1N *CL



19/65

Results

Ta+l" 3.1@, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch P i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.01 0.0'6 0.01 '3.4$ '3.4$ 4.54

2. ' 0.'$' 0.021 0.'3 2$.05 2$.'' '2.$$

5. 2 0234 0.036 0.25 30.3 3'.'6 20.$1

3. 5 0.246 0.0$' 02$ 3$.4$ 36.' 25.'0

$. 3 0.502 0.0$6 0.21 $0.06 $0.46 2$.51

6. $ 0.551 0.062 0.5' $6.02 $4.00 21.$0

4. 6 0.56 0.061 053 6'.2 62.3$ 5'.22

1. 4 0.3'$ 0.46 051 61.41 40.3' 5$.2'

. 1 0.354 0.010 030 42.35 43.35 54.22

'0. '0 0.313 0.1 0.3$ 10.22 12.65 3'.5'

''. '2 0.$53 0.01 0.3 11.$' '.0 3$.$$


0

10

20

30

40

50

0 5 10 15

Time(hrs)

% C u m . d r u g r e l e a s e

Fi( 3.18, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch P i% >.1N *CL

5.5.5.7. In-Vitro )elease ata of Theophylline from ifferent ,ormulations "repared

with *"87 C '00 8 alone and in combination with ehusk+ *usk "syllium in 0.'9

*7

Dept. of Pharmaceutical Sciences S.S.I.T.M.1'


20/65

Results

Ta+l" 3.>, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch * i% >.1N *CL

S.N). Ti!"2hs5 A+s)+. C)%c"%#a#i)% 2!(5 C!. &("l"as" 6 C!.&(

"l"as"!l : !l @>> !l

'. 0.$ 0.01 0.'1 0.0 '6.23 '6.23 1.'2

2. ' 0.'46 0.52 0'6 2.'4 2.26 '3.6

5. 2 0.253 0.035 0.24 51.4 5.03 '.$2

3. 5 0.50' 0.0$3 0.21 $0.3 $0.14 2$.33

$. 3 0.5$1 0.66 0.55 $.53 60.'0 50.0$

6. $ 0.32' 0.41 0.511 6.41 40.16 5$.35

4. 6 0.36' 0.01$ 0.323 46.3' 44.11 51.3

1. 4 0.31 0.2 0.36 12.$3 13.33 32.22

. 1 0.$ 0.'' 0.$$ .00 '0'.5$ $0.61

'0. '0 0.641 0.'2$ 0.65 ''2.54 ''$.21 $4.65

''. '2 0.61 0.'2 0.63 ''$.6 ''1.3 $.34


0

10

20

30

40

50

60

70

0 5 10 15

Time(hrs)

%

C u m .


Fi( 3.1:, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch * i% >.1N *CL



21/65

Results

Ta+l" 3.1, In-Vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DP* i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.'20 0.0'13 0.0 '6.6 '6.6 1.5

2. ' 0.20' 0.0540 0.' 55.5' 55.3' '6.4

5. 2 0.2$' 0.036' 0.25 3'.6 3'.11 20.5

3. 5 0.5'' 0.0$45 0.2 $'.$$ $2.0$ 26.05

$. 3 0.56 0.061 0.53 6'.'6 6'.$ 50.1

6. $ 0.355 0.04 0.5 4'.45 42.14 56.35

4. 6 034' 0.014 0.35 41.04 4.6 5.10

1. 4 0.$54 0.01 0.3 1.0' 0.3 3$.34

. 1 0.$6$ 0.'03 0.$2 5.6$ 6.'' 31.0$

'0. '0 0.$14 0.'01 0.$3 4.2 '00.21 $0.'3

''. '2 0.642 0.'53 0.62 '''.51 ''3.' $4.3$


0

10

20

30

40

50

60

70

0 5 10 15

Time(hrs)

%

C u m .


Fi( 3.1?, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch DP * i% >.1N

*CL



22/65

Results

Ta+l" 3., In-Vitro "l"as" Da#a )0 #h")phylli%" 0)! +a#ch P* i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.'04 0.0'4 0.0 '4.45 '4.45 1.16

2. ' 0.2'5 0.05 0.'6 5$.5 5$.3 '4.4

5. 2 0.212 0.0$2 0.26 36.43 34.03 25.$'

3. 5 0.5'' 0.0$4 0.2 $'.$$ $2.' 26.0$

$. 3 0.564 0.061 0.53 60.15 6'.64 50.15

6. $ 0.321 0.04 0.5 40.3 42.05 56.02

4. 6 033 0115 0.3' 43.35 4$. 51.

1. 4 0.$2$ 0.064 0.31 14.02 11.1 33.3$

. 1 0.$35 0.'00 0.$0 0.0 2.56 36.'1

'0. '0 0.$64 0.'03 0.$2 5.1 6.13 31.32

''. '2 0.6'1 0''3 0.$4 '02.35 '0$.1' $2.'


0

10

20

30

40

50

60

0 5 10 15

Tme(hrs)

%

C u m .

d r u g r e l e a

s e

Fi( 3.1, In-Vitro "l"as" )0 #h")phylli%" 0)! +a#ch P * i% >.1N *CL

5.5.5. In-Vitro )elease ata of Theophylline from ifferent ,ormulations "repared

with Ac-i-!ol in combination with ehusk+ and *usk "syllium in 0.'9 *7



23/65

Results

Ta+l" 3.3, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DPC1 i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.6 0.0'44 0.011 '$.' '$.' 4.$

2. ' 0.'13 0.055 0.'4 50.$0 50.$ '$.2

5. 2 0.2$$ 0.34'0 0.25$ 32.24 32.$2 2'.26

3. 5 0.5'4 0.0$13 0.22 $2.$3 $5.05 26.$2

$. 3 0.531 0.063 0.52 $4.61 $1.36 2.25

6. $ 0.53 0.045 0.565 6$.61 66.3' 55.2'

4. 6 0.32 0.04 0.5$ 4'.'0 42.$4 56.2

1. 4 0.3$2 0.015 0.3'6 43.3 46.6' 51.5'

. 1 0.$26 0.06 0.310 14.'1 1.25 33.6'

'0. '0 0.$4 0.'066 0.$55 $.4 1.45 3.56

''. '2 0.634 0.'' 0.$6 '04.23 ''0.$5 $$.24


0

10

20

30

40

50

60

0 5 10 15

Time(hrs)

%

C u m .


Fi( 3.1, In-vitro "l"as" )0 #h")phylli%" 0)! +a#ch DPC1 i% >.1N *CL



24/65

Results

Ta+l" 3.8, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch DPC i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.'0' 0.0'16 0.5 '6.43 '6.43 1.54

2. ' 0.'11 0.5$ 0.'45 5'.'6 5'.2$ '$.65

5. 2 0.24$ 0.0$' 0.2$5 3$.$1 3$.1$ 22.2

3. 5 0.526 0.06 0.5 $3.05 $3.$$ 24.21

$. 3 0.566 0.064 0.53 60.66 6'.31 50.43

6. $ 0.3'2 0.046 0.54 61.2 6.3$ 53.42

4. 6 0.363 0.01$ 0.324 46.' 41.33 5.22

1. 4 0.$'2 0.03 0.34 13.16 16.15 35.3'

. 1 0.$$2 0.'02 0.$01 '.3 5.5 36.6

'0. '0 0.631 0.'' 0.$4 '04.3 ''0.5$ $$.'4

''. '2 0.4'' 0.'5' 0.66 ''4.1$ '20.02 60.0'


0

10

20

30

40

50

60

70

0 5 10 15Time(hrs)

%

C u m . d r u g r e l e a s e

Fi(3.1@, In-vitro "l"as" )0 #h")phylli%" 0)! +a#ch DPC i% >.1N *CL



25/65

Results

Ta+l" .:, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch PC1 i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.0' 0.0'4 0.01 '$.01 '$.01 4.$3

2. ' 0.'16 0.053 0.'4 50.14 50.$ '$.31

5. 2 0.24 0.0$' 0.26 36.23 36.3 25.2$

3. 5 0.52$ 0.060 0.50 $2.14 $3.51 24.'

$. 3 0.563 0.064 053 60.5' 6'.'2 50.$6

6. $ 0.30$ 0.04$ 0.54 64.'5 61.2 53.'3

4. 6 0.324 0.04 0.5 40.44 42.2 56.'3

1. 4 0.3$' 0.015 0.32 43.4$ 46.66 51.55

. 1 0.$'2 0.03 0.34 13.16 14.'1 35.$

'0. '0 0.$$2 0.'02 0.$2 '.12 3.62 34.5'

''. '2 0.601 0''2 0.$6 '00.44 '03.01 $2.03


0

10

20

30

40

50

60

0 5 10 15

Time(hrs)

%


Fi( 3.>, In-vitro "l"as" )0 #h")phylli%" 0)! +a#ch PC1 i% >.1N *CL



26/65

Results

Ta+l" 3.?, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! +a#ch PC i% >.1N *CL

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l'. 0.$ 0.''2 0.02' 0.'5 '1.$6 '1.$6 .21

2. ' 0.'3 0.026 0.'1 52.'6 5'.26 '6.'5

5. 2 0.212 0.$20 0.24 36.43 34.02 25.$'

3. 5 0.552 0.6'0 0.5' $$.05 $$.$1 24.4

$. 3 0.562 0.064 0.55 60.00 60.16 50.35

6. $ 0.323 0.041 0.0.5 40.21 4'.34 5$.45

4. 6 00.54 0.01' 0.3 42.35 43.03 54.0'

1. 4 0.34 0.110 033 4.5 1'.56 30.6

. 1 0$55 0.01 0.3 11.53 0.46 3$.51

'0. '0 0.6'0 0.''2 0$6 '0'.'' '05.4$ $'.14

''. '2 0.616 0.'26 0.65 ''5.30 ''6.5 $1.'$


0

10

20

30

40

50

60

70

0 5 10 15

Time(hrs)

%


Fi( 3.1, In-vitro "l"as" )0 #h")phylli%" 0)! +a#ch PCi% >.1N *CL

3.3.8, D"#"!i%a#i)% )0 S7"lli%( I%&"9: - The swelling indeD of the tablets was

studied using the !" dissolution apparatus (. The dissolution medium was 0.'9 *7

and the volume being 00 ml. The temperature was maintained at 54 #0. $

0

7. The



27/65

Results

rotation speed '00 rpm. The tablets were withdrawn at predetermine intervals of '+ 2+

5+ 3+ $+ 6 E.'2 hrs. The tablets were blotted with tissue paper to remove the eDcess

0.'9 *7 and reweighed. The swelling indeD was calculated by the following

e=uation: '05+'03+'0$

!welling indeD % Ft - Fo Fo & / '00

Fhere: Ft is the weight of swelling matriD tablet after t times

Fo is the initial weight of matriD tablet

Ta+l" 3., S7"lli%( i%&"9 )0 #h")phylli%" 0l)a#i%( !a#i9 #a+l"#s 0)! &i00""%#

0)!la#i)%s i% >.1N *CL

S.N)

F)!la#i)

% c)&"

I%i#ial

7"i(h

#

2!(5

P"c"%#a(" )0 s7"lli%( i%&"9

Ti!" 2hs5

1 3 8 ?

1

'. "5 452 $4.' '5'.$$ 2''.3 240.3 506.2 553.

543.'4

2. "3 452 40. '5.2' 223.0 26.31 21.31 523.1

501.'

5. "5 452 36.05 ''4.43 '12.23 2$$.$ 5'1.'6 531.'$

5'4.25

3. "3 452 $1.3 '26.66 '1.31 231.1 24.1 55.5

506.'2

$. * 452 1$.2 '56.66 '40.34 22$.41 221.15 224.4

2'$.'5

6. "72 42 41.'3 '3$.'' 22$.0 24'.'' 501.0 53.''

5'2.$

4. "72 42 6$.'2 '50.6' 2'0.0 2$.' 5'.1 5$$.'

5'4.'1

% 1



28/65

Results

Fi( 3., S7"lli%( i%&"9 )0 #h")phylli%" 0l)a#i%( !a#i9 #a+l"#s 0)!

&i00""%# 0)!la#i)%s i% >.1N *CL

3.3.:. E)si)% S#&i"s, - Grosion studies of floating matriD tablets were performed as

reported by "aradkar et al. The preweighed tablets were placed in !" dissolution

Type ( dissolution test apparatus and were subHected to dissolution in 00 ml of 0.'9

*7 maintained at 54-7 # 0.$-7+ the speed of basket rotation was '00 rpm. The

matriD system were removed after '2 hrs from the dissolution vessels and dried to

constant weight in hot air oven %*icon+ (ndia& at $007 - 60 07. The percentage matriD

erosion at time '2 hrs was calculated by using following G=uation: '05+'03+'0$

"ercentage 8atriD Groded %wt of polymers eroded wt of initial matriD& /'00

Feight of polymers eroded total weight loss I amount of drug released



29/65

Results

Ta+l" 3., P"c"%#a(" !a#i9 ")&"& a0#" 1 hs 0)! &i00""%# 0)!la#i)% i%

>.1N *CL

S.N). F)!la#i)%

c)&"

Ta+l"# 7"i(h# 2!(5 T)#al7"i(h#

l)ss

2!(5

D("l"as"&

2!(5

Ma#i9")&"&

2!(5

P"c"%#a(")0 !a#i9

")&"&i%i#ial "!ai%i%(

&yi%( 7"i(h#

'. "5 45$ $16 '3 5.2 $$.01 4.3

2. "3 45' $' '30 6.1 35.02 $.14

5. * 455 $1$ '31 '5'.26 '6.43 2.21

3. "5 456 $41 '$1 1.11 61.'2 .2$

$. "3 452 $11 '33 2.2 $'.06 6.4

6. "72 40 654 '$4 '2'.5 5$.4 3.3

4. "72 43 6'6 '43 '53.3 5.6 $.0'

n '

Fi( 3.3, P"c"%#a(" !a#i9 ")&"& a0#" 1 hs 0)! &i00""%# 0)!la#i)%s

i% >.1 N *CL

Dept. of Pharmaceutical Sciences S.S.I.T.M.'


30/65

Results

Ta+l" 3.@, Chaac#"i$a#i)% )0 &i00""%# +a#ch"s

S.N) F)!la#i)%

c)&"

Fl)a#a#i)% +"ha/i)

'. "' Tablets floated with significant floating lag time good swelling but

not intact+ not release the drug up to 23 hrs.

2. "2 Tablets floated with significant floating lag time+ good swelling but


5. "5 Tablets floated with significant floating lag time+ good swelling+

remained intact throughout the study+ higher erosion+ release the drug

up to 23 hrs.

3. "3 Tablets showed good buoyancy with good swelling+ remained intactthroughout the study+ reduced erosion+ floating lag time

comparatively reduced+ release the drug up to 23 hrs.

$. "$ Tablets showed good buoyancy with good swelling+ remained intact

throughout the study+ reduced erosion+ floating lag time


6. "6 Tablets floated with good swelling+ not remained intact throughout

the study and significant floating lag time.

4. "4 Tablets showed good buoyancy with good swelling+ remained intactthroughout the study+ floating lag time reduced.

1. "* Tablets showed good buoyancy with good swelling+ remained intact

throughout the study+ floating lag time comparatively reduced.

. * Tablets showed good buoyancy with good swelling+ remained intact

throughout the study+ floating lag time was lowest+ lowest erosion+

release the drug up to 23 hrs.

'0. "' Tablets floated with significant floating lag time+ good swelling but


''. "2 Tablets floated with significant floating lag time+ good swelling but


'2. "5 Tablets floated with significant floating lag time+ good swelling

remained intact+ highest erosionJ release the drug up to 23 hrs.

'5. "3 Tablets showed good buoyancy with good swelling+ remained intact

throughout the study+ reduced erosion+ floating lag time


'3. "$ Tablets showed good buoyancy with good swelling+ remained intact



31/65

Results

throughout the study reduced erosion+ floating lag time comparatively

reduced+ release the drug up to 23 hrs.

'$. "6 Tablets floated with good swelling+ not remained intact through the

study and and significant floating lag time.

'6. "4 Tablets showed good buoyancy with good swelling+ remained intact

throughout the study+ floating lag time reduced+ release the drug up to

23 hrs.

'4. "* Tablets showed good buoyancy with good swelling+ remained intact

throughout the study+ reduced erosion+ floating lag time reduced+

release the drug up to 23 hrs.

'1. "7' Tablets showed good buoyancy with good swelling+ remained intact

throughout the study+ floating lag time reduced+ release the drug up to23 hrs.

'. "72 Tablets showed good buoyancy with good swelling+ remained intact

through the study+ floating lag time reduced+ showed the release up to

the 23 hrs.

20. "7' Tablets showed good buoyancy with good swelling+ remained intact

throughout the study+ floating lag time reduced+ release the drug up to

23 hrs.

2'. "72 Tablets showed good buoyancy with good swelling+ remained intactthroughout the study+ floating lag time reduced+ showed the release up

to the re=uired period of time.

3.3.8. STUD< ON OPTIMIZED FORMULATIONS

3.3.8.A E00"c# )0 *a&%"ss )% B)ya%cy

Ta+l"3.3>, E00"c# )0 ha&%"ss )% +)ya%cy 0)! &i00""%# 0)!la#i)%s

S.N). Ba#ch c)&" *a&%"ss

2(4c!5

Fl)a#i%( capa+ili#i"s

Fl)a#i%( la(

Ti!" 2s"c.5

0l)a#i%(

&a#i)%2hs5

'. "72 2 3$#2 23

3 '0±5 23

6 9, -

2.

"72

2 $0 ±1.63 23



32/65

Results

3 200±8 23

6 9, -

5. * 2 0 23

3 '0.5±1.53 23

6 0.4$ 23

9, note float+ 8ean ± SD, n = 3

3.3.8 B E00"c# )0 RPM )% In-vitro D( R"l"as"

Ta+l" 3.31, In-vitro "l"as" &a#a )0 &( "l"as" 0)! +a#ch DPC a# :> RPM

S.N). Ti!"

2hs5

A+s)+. C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"

!l : !l @>> !l

'. 0.$ 0.01 0.0'34 0.0454 '5.26 '5.26 6.65

2. ' 0.'66 0.050$ 0.'$2 24.$' 24.$1 '5.4

5. 2 0.253 0.035' 0.2'$$ 51.41 51.$ '.31

3. 5 0.524 0.0602 0.50'0 $3.2 $3.63 24.52

$. 3 0.555 0.06'5 0.5064 $$.'4 $$.66 21.$1

6. $ 0.3'' 0.04$4 0.5410 61.'2 61.4$ 53.54

4. 6 0.33' 0.01'2 0.306' 45.0 43.2$ 54.'5

1. 4 0.361 0.0162 0.35'0 44.$1 4.'3 5.$4

. 1 0.$'0 0.05 0.366 13.$5 16.$2 35.26

'0. '0 0.605 0.'''' 0.$$$$ . '02.'2 $'.06

''. '2 0.64' 0.'253 0564 '''.25 ''3.$2 $4.26




33/65

Results

Fi( 3.8, In-vitro "l"as" )0 #h")phylli%" 0)! +a#ch DPC a# :> RPM

Ta+l" 3.3, In-vitro "l"as" &a#a )0 &( "l"as" 0)! +a#ch PC a# :> RPM

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as" !l : !l @>> !l

'. 0.$ 0.0 0.0'66 0.12 '3.2 '3.2 4.36

2. ' 0.'15 0.0533 0.'42 50.6 5'.03 '$.$2

5. 2 0.2$' 0.362 0.25' 3'.6 3'.16 20.5

3. 5 0.210 0.0$'6 0.2$1 36.3' 36.1 25.3$$. 3 0.535 0.0652 0.5'$1 $6.1$ $4.$ 21.4

6. $ 0.305 0.0432 0.54'' 66.4 64.16 55.5

4. 6 0.3'2 0.04$ 0.543 61.21 6.42 53.16

1. 4 0.342 0.016 0.35$ 41.2' 10.02 30.0'

. 1 0.$'0 0.05 0.366 13.$5 16.41 35.5

'0. '0 0.60' 0.''' 0.$$$$ .6' '0'.1 $0.$

''. '2 0.61. 0.'226 0.6'55 ''0.3' ''5.34 $6.4'


Fig3.25: In-vitro "l"as" )0 #h")phylli%" 0)! +a#ch PC a# :> RPM

Dept. of Pharmaceutical Sciences S.S.I.T.M.$


34/65

Results

Ta+l" 3.33, In-vitro "l"as" &a#a )0 &( "l"as" 0)! +a#ch * a# :> RPM

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&(

"l"as"!l : !l @>> !l

'. 0.$ 0.0 0.0'66 0.015 '3.2 '3.2 4.36

2. ' 0.'1$ 0.053' 0.'40 50.66 50.43 '$.5

5. 2 0.23' 0.0333 0.222 5.3 30.' 20.'

3. 5 0.26 0.0$3$ 0.245 3.06 3.$3 23.44

$. 3 0.562 0.6664 0.555 60.0 60.4$ 50.546. $ 0.3' 0.4420 0.51$ 6.3$ 40.$5 5$.26

4. 6 0.335 0.0120 0.301 45.35 43.1 54.3$

1. 4 0.312 0.1110 0.333 4.2 1'.4 30.1

. 1 0.$3' 0.06 0.31 1.64 2.54 31.'1

'0. '0 0.6'3 0.''5' 0.$6$ '0'.4 '03.6 $2.5

''. '2 0.612 0.'2$6 0.621 ''5.03 ''6.32 $1.2'


Fi(3.?, In-vitro "l"as" )0 #h")phylli%" 0)! +a#ch * a# :> RPM

3.3.8.C. I%#"ac#i)% S#&y 3.3.8.C.I Thi% lay" Ch)!a#)(aphy: - (t was concluded that there was no

significant changed in ) f value of theophylline alone and with polymer. The ) f was

found to be 0.66$+0.64 and 0.61$ for *+ "72 and "72 respectively.



35/65

Results

3.3.8.C.II F)i" Ta%s0)! I%0a"& Sp"c#)sc)py: - () !pectroscopy is of

immense value in establishing drug polymer interaction in solid state. The origin of

any new sharp () peak or disappearance of any peak associated with a functional

group of the pure drug indicates the drug and polymer in solid state %Techibana and

9eekamura. '6$&.

() spectra of the pure drug and optimized formulations eDhibit the following

absorption band.

Ta+l"3.38, 'a/"l"%(#h /al"s )0 &( i% #h" IR sp"c#a

S.N).'a/"l"%(#h 2c!

-1

5Assi(%!"%#R"0""%c"

a%("

O+s"/"& /al/"

P" &( F)!la#i)%

'. 5500-5$00 5325 53$0 9-*%stretch&

2. '6$0-'4$0 '4'2 '4'2 7K%stretch&

5. '6$0-'64$ '666 '664 77%stretch&

3. '$$0-'$4$ '$65 '$63 79%stretch&

$. '300-'$00 '335 '335 7-*%bending&

6. '2$0-'500 '212 '216 7-9%vibration&

4. '200-'2$0 '230 '23' 7-K%vibration

1. 400-00 135 13' 7-* out plan bending

%A&



36/65

Results

%;&

Fi( 3., I.R. Sp"c#a )0 2A5 Psylli! hs 2B5 Op#i!i$"& 0)!la#i)%



37/65

Results

3.3.8. D R"l"as" i%"#ics

Ta+l" 3.3:, R"l"as" i%"#ics 0) 0)!la#i)% DPC

S.

N).

Ti!"

2hs5

Sa"

))#

#i!"

2hs5

L)(

#i!"

2hs 5

C!la#i/

"

6 &(

"l"as"

L)(

c!la#i/

" 6 &(

"l"as"

L)(

c!la#i/"

6 &(

"!ai%i%(

C+" ))#

c!la#i/"

6 &(

"!ai%i%(

' 0.$ 0.4' -0.50' 1.54 0.2 '.6 3.$'

2 '.0 ' 0 '$.65 '.' '.5 3.5

5 2.0 '.3' 0.50' 22.2 '.56 '.1 3.26

3 5.0 '.45 0.344 24.21 '.33 '.16 3.'4

$ 3.0 2 0.60 50.43 '.3 '.13 3.''

6 $.0 2.23 0.4 53.42 '.$3 '.12 3.05

4 6.0 2.3$ 0.41 5.22 '.$ '.41 5.5

1 4.0 2.6$ 0.1$ 35.3' '.63 '.4$ 5.13

1.0 2.15 0. 36.6 '.64 '.42 5.46

'0 '0 5.'6 ' $$.'4 '.43 '.6$ 5.$$

'' '2 5.36 '.' 60.0' '.41 '.6 5.3'

Ta+l" 3.3?, R"l"as" paa!"#"s )0 )p#i!i$"& 0)!la#i)% DPC

Z") )&" Fis# )&" *i(chi )s!"y"-

P"ppas

*i9s)%-

C)7"ll

>

2h-15

1

2h-15

*

2h-145

%

/al"

*C

2h-1435

0.3$ 3.24$' 0.$3 0.0402 0.4 '1.25 0.2' 0.$322 0.' 0.02

Dept. of Pharmaceutical Sciences S.S.I.T.M.


38/65

Results

2A5 Z") )&" !)&"l

2B5Fis# )&" !)&"l

2C5 *i(chi !)&"l

Dept. of Pharmaceutical Sciences S.S.I.T.M.'00


39/65

Results

2D5 *i9s)% C)7"ll !)&"l

2E5 )s!"y"-P"ppas !)&"l

Fi(3., R"l"as" i%"#ics 0) 0)!la#i)% DPC

Ta+l"3.3, R"l"as" i%"#ics )0 0)!la#i)% PC

S.

N).

Ti!"

2hs5

Sa"

))#

#i!"

2hs5

L)(

#i!"

2hs 5

C!la#i/

"

6 &(

"l"as"

L)(

c!la#i/

" 6 &(

"l"as"

L)(

c!la#i/"

6 &(

"!ai%i%(

C+" ))#

c!la#i/"

6 &(

"!ai%i%(

' 0.$ 0.4' -0.50' .21 0.4 '.6 3.32 '.0 ' 0 '6.'5 '.2' '.2 3.51

5 2.0 '.3' 0.50' 25.$' '.54 '.11 3.23

3 5.0 '.45 0.344 24.4 '.$1 '.16 3.'1

$ 3.0 2 0.60 50.35 '.31 '.13 3.''

6 $.0 2.23 0.4 5$.45 '.$$ '.1' 3.02

4 6.0 2.3$ 0.41 54.0' '.$4 '.1 5.1

1 4.0 2.6$ 0.1$ 30.6 '.6' '.44 5.

1.0 2.15 0. 3$.52 '.66 '.45 5.4

'0 '0 5.'6 ' $'.14 '.42 '.61 5.65

'' '2 5.36 '.' $1.'$ '.44 '.62 5.36

Dept. of Pharmaceutical Sciences S.S.I.T.M.'0'


40/65

Results

Ta+l" 3.3, R"l"as" paa!"#"s )0 )p#i!i$"& 0)!la#i)% PC

Z") O&" Fis# O&" *i(chi )s!"y"-

P"ppas

*i9s)%-

C)7"ll

>

2h-15

1

2h-15

*

2h-145

%

/al"

*C

2h-1435

0.406 5.601 0.116 0.065 0.0' '6.

'5

0.13 0.$'36 0.1 0.015$

2A5 Z") )&" !)&"l

2B5 Fis# )&" !)&"l



41/65

Results

2C5 *i(chi !)&"l

2D5 *i9)% C)7"ll !)&"l

2E5 )s!"y"-P"ppas

Fi( 3.@, R"l"as" i%"#ics 0) 0)!la#i)% PC



42/65

Results

Ta+l" 3.3@, R"l"as" i%"#ics )0 0)!la#i)% *

S.

N).

Ti!"

2hs5

Sa"

))#

#i!"

2hs5

L)(

#i!"

2hs 5

C!la#i/

"

6 &(

"l"as"

L)(

c!la#i/

" 6 &(

"l"as"

L)(

c!la#i/"

6 &(

"!ai%i%(

C+" ))#

c!la#i/"

6 &(

"!ai%i%(

' 0.$ 0.4' -0.50' 1.'2 0.' '.6 3.$'

2 '.0 ' 0 '3.65 '.'4 '.5 3.3

5 2.0 '.3' 0.50' '.$2 '.2 '.' 3.52

3 5.0 '.45 0.344 2$.33 '.30 '.14 3.2'

$ 3.0 2 0.60 50.0$ '.31 '.13 3.'2

6 $.0 2.23 0.4 5$.35 '.$$ '.1' 3.0'

4 6.0 2.3$ 0.41 51.3 '.$ '.41 5.3

1 4.0 2.6$ 0.1$ 32.22 '.62 '.46 5.16

1.0 2.15 0. $0.61 '.4 '.4 5.61

'0 '0 5.'6 ' $4.54 '.46 '.65 5.3

'' '2 5.36 '.' $.61 '.34 '.6' 5.35

Ta+l" 3.8>, R"l"as" paa!"#"s )0 )p#i!i$"& 0)!la#i)% *

Z") O&" Fis# O&" *i(chi )s!"y"-

P"ppas

*i9s)%-C)7"ll

>2h-15

12h-15

*2h-145

%

/al"

*C2h-1435

0.456 3.$$6 0.15 0.0424 0.' '.$61 0.21 0.6331 0.1$4 0.04$

2A5 Z") )&" !)&"l



43/65

Results

2B5 Fis# )&" !)&"l

2C5 *i(chi !)&"l

2D5 *i9)% C)7"ll !)&"l

Dept. of Pharmaceutical Sciences S.S.I.T.M.'0$


44/65

Results

2E5 )s!"y"-P"ppas

Fi( 3.3>, R"l"as" i%"#ics 0) 0)!la#i)% *

3.3.8.E C)!paa#i/" in-Vitro D( "l"as" S#&y )0 Th")phylli%" a0#" 1 hs

0)! Op#i!i$"& F)!la#i)%s 7i#h #h" *"lp )0 S#a#is#ical A%alysis 2O%" 'ay

ANOVA5

Ta+l" 3.81, ANOVA

S)c" )0

i%0)!a#i)%

S! )0

sa"s

D"("" )0

0""&)!

M"a% s!

)0 sa"s

Calcla#"&

F /al"

Ta+l" /al"

)0 F

;etween the

formulation 5.2 2 '.6 '.'6

F ? $.'3

at $ B level

of

significance

Fith in the

formulation 4.01 6 '.'1

Total '' 1



45/65

Results

I%#"p"#a#i)%, - The calculated , value %1.1?& is less than that of table value %:.185

a# : 6 level of significance %H >.>:5. !o 9ull hypothesis was accepted. There was

no significance difference between the B drug released from different optimized

formulations.

3.3.8.F. S#a+ili#y S#&y: - !tability study was conducted on only optimized

formulations. The formulation were packed in the aluminium foil and subHected to

stability studies at different temperature and humidity conditions as per the (7*

guidelines viz room temperature %2$0 760B )*& and 3007 4$B)*. The sample

was withdrawn at time intervals of 0+ '$+ 50 days. The sample was evaluated for

possible weight variation+ drug contents+ floating lag time and in vitro release profile.

Ta+l" 3.8, Physical chaac#"is#ics )0 #h")phylli%" 0l)a#i%( !a#i9 #a+l"# )0

+a#ch DPC "p# a# ))! #"!p"a#" 0) 3> &ays

Physical

paa!"#"s

Ba#ch c)&" DPC

> &ays 1: &ays 3> &ays

Feight gain %mg& 4'.25 # '.33 4'.22#'.'5 4'.23#'.3

"ercentage drug

content

1.3#0.$' .5#0.62 .1'#0.$2

Ta+l" 3.83, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! 0l)a#i%( !a#i9 #a+l"#s )0

+a#ch DPC i% >.1N *CL "p# a# R))! #"!p"a#" 3> &ays

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"

!l : !l @>> !l

'. 0.$ 0.'04 0.0' 0.0 '4.' '4.' 1.$$

2. ' 0.'2 0.05$ 0.'4 5'.$ 5'.$ '$.10

5. 2 0.24' 0.03 0.23 33.' 33.54 22.'3. 5 0.5'2 0.0$4 0.21 $'.5 $'.12 2$.'

$. 3 0.564 0.061 0.53 6'.2 62.0 5'.0

6. $ 0.3'2 0.046 0.51 61.3 6.$3 53.46

4. 6 0.36' 0.013 0.32 4$.6 44.'2 51.$6

1. 4 0.$'3 0.0$ 0.3$ 1$.$ 14.33 35.42

. 1 0.$$ 0.'05 0.$' 2.4 $.'4 34.$6

'0. '0 0.635 0.''1 0.$ '06.2 '01.1 $3.3$

''. '2 0.4'5 0.'5' 0.6$ ''4. '2'.5 60.4




46/65

Results


+a#ch PC "p# a# ))! #"!p"a#" 0) 3> &ays

Physical

paa!"#"s

Ba#ch c)&" PC


Feight gain %mg& 42.5#2.'3 42.3'#2.' 42#2.36

"ercentage drug

content

.$'#'.62 .3'#'.6' .2#'.2'

Ta+l" 3.8:, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! 0l)a#i%( !a#i9 #a+l"#s )0

+a#ch PC i% >.1N *CL "p# a# ))! #"!p"a#" 3> &ays

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"

!l : !l @>> !l

'. 0.$ 0.''3 0.02' 0.'0$ '1. '1. .3$

2. ' 0.'6 0.056 0.'10 52.3 52.$' '6.26

5. 2 0.251 0.0$2 0.262 36.1 34.0 25.$$

3. 5 0.55' 0.06' 0.50$ $3. $$.3$ 24.45

$. 3 0.563 0.064 0.55$ 60.$ 6'.'$ 50.$4

6. $ 0.35$ 0.010 0.300 42.2 45.24 56.63

4. 6 0.3$ 0.01$ 0.32$ 46.$ 41.01 5.03

1. 4 0.34' 0.0 0.35 44.33 4.3' 5.4

. 1 0.$51 0.016 0.3$ 1.' '.$3 3$.44

'0. '0 0.6'5 0.0''5 0.$6$ '0'.4 '0$.2 $2.60''. '2 0.61' 0.'2$ 0.62$ ''2.$ ''6.0 $1.0


Ta+l" 3.8?, Physical chaac#"is#ics )0 #h")phylli%" 0l)a#i%( !a#i9 #a+l"# )0

+a#ch * "p# a# ))! #"!p"a#" 0) 3> &ays

Physical

paa!"#"s

Ba#ch c)&" *


Feight gain %mg& 42.'#2.'1 452.'5#2.2$ 452.''#2.''

"ercentage drug

content

.53#'.' .'4#'.2 .'5#'.54

Ta+l" 3.8, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! 0l)a#i%( !a#i9 #a+l"#s )0

+a#ch * i% >.1N *CL "p# a# ))! #"!p"a#" 3> Days

S.N). Ti!"

2hs5

A+s)+. C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"

!l : !l @>> !l

'. 0.$ 0.05 0.0'4 0.01 '$.5 '$.1 4.6$

2. ' 0.'4' 0.05$ 0.'4 5'.$ 5'.$1 '$.6

5. 2 0.253 0.035 0.2' 51.4 51.6 '.31

3. 5 0.50$ 0.0$6 0.21 $0.3 $0.14 2$.35

$. 3 0.5$5 0.06$ 0.52 $1.$ $.2$ 2.65



47/65

Results

6. $ 0.32$ 0.041 0.5 40.2 4'.21 5$.62

4. 6 0.36' 0.01$ 0.32 46.$ 44.4 51.1

1. 4 0.31 0.0' 0.3$ 1'. 15.4 3'.1

. 1 0.$ 0.''0 0.$$ .0 '0'.5$ $0.64

'0. '0 0.641 0.'2$ 0.65 ''2.$ ''$.3 $4.4

''. '2 0.403 0.'2 0.63 ''6.' ''.65 $.14



+a#ch DPC "p# a# 8>>C 4 : 6 R* 0) 3> &ays

Physical

paa!"#"s

Ba#ch c)&" DPC


Feight gain %mg& 45.'6#'.4 43.'5#'.12 43.'#'.'5

"ercentage drug

content

1.2#0.2' 1.63#0.5 1.5'#0.61



48/65

Results

Ta+l" 3.8@, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! 0l)a#i%( !a#i9 #a+l"#s )0

+a#ch DPC i% >.1N *CL "p# a# 8>> C4 : 6R* 0) 3> Days

S.N). Ti!"

2hs5

A+s)+

.

C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"

!l : !l @>> !l

'. 0.$ 0.'0 0.02 0.' '1.0 '1

2. ' 0.'' 0.05$ 0.'4 5'.$ 5'.6 '$.1

5. 2 0.26 0.03 0.23 33.' 33.54 22.'1

3. 5 0.501 0.0$6 0.21 $0.3 $0.2 2$.36

$. 3 0.56' 0.066 0.55 $.3 60.' 50.0

6. $ 0.3'$ 0.046 0.51 61.1$ 6.1 53.

4. 6 0.364 0.016 0.35 44.3 4.1' 5.'

1. 4 0.$'3 0.0$ 0.34 1$.$ 14.33 35.42

. 1 0.$65 0.'03 0.$2 5.6 6.02 31.0'

'0. '0 0.63' 0.''1 0.$ '06.2 '0.'3 $3.$4

''. '2 0.4'$ 0.'52 0.66 ''1.1 '22.5 6'.'6Total amount of drug 200 mg+ dilution factor '0 slope 0.0$35

Ta+l" 3.:>, Physical chaac#"is#ics )0 #h")phylli%" 0l)a#i%( !a#i9 #a+l"# )0

+a#ch PC "p# a# 8>>C 4: 6 R* 0) 3> &ays

Physical

paa!"#"

Ba#ch c)&" PC


Feight gain %mg& 42.36#'.25 45.''#'.'3 45.$1#'.3'

"ercentage drug

content

.63#0.'2 .$#0.5' .2#0.3

Ta+l" 3.:1, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! 0l)a#i%( !a#i9 #a+l"#s )0

+a#ch PC i% >.1N *CL "p# a# 8>> C4 : 6 R* 0) 3> Days

S.N). Ti!"

2hs5

A+s)+. C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"!l : !l @>> !l

'. 0.$ 0.''2 0.02' 0.'' '1. '1. .3$

2. ' 0.'' 0.5$ 0.'4 5'.$ 5'.6' '$.1'

5. 2 0.21' 0.0$2 0.26 36. 34.01 25.$33. 5 0.524 0.060 0.50 $3.0 $3.$3 24.24

$. 3 0.56' 0.66 0.55 $.3 60.23 50.'2

6. $ 0.35' 0.04 0.5 4'.' 42.24 56.'3

4. 6 0.3$ 0.01$ 0.32 46.$ 41.04 5.05

1. 4 0.36$ 0.016 0.35 44.3 4.5 5.6

. 1 0.$5' 0.04 0.3 11.2 0.62 3$.5'

'0. '0 0.60' 0.''' 0.$$ . '02.1' $'.3

''. '2 0.61' 0.'26 0.65 ''5.3 ''6.16 $1.35


Dept. of Pharmaceutical Sciences S.S.I.T.M.''0


49/65

Results

Ta+l" 3.:, Physical chaac#"is#ics )0 #h")phylli%" 0l)a#i%( !a#i9 #a+l"# )0

+a#ch * "p# a# 8>>C : 6 R* 0) 3> &ays

Physical

paa!"#"

Ba#ch c)&" *


Feight gain %mg& 453.'3#'.13 453.'3#'.1 45$#'.23

"ercentage drug

content

.'2#0.$ 1.'#0.$6 1.'2#0.$'

Ta+l" 3.:3, In-vitro "l"as" &a#a )0 #h")phylli%" 0)! 0l)a#i%( !a#i9 #a+l"#s )0

+a#ch * i% >.1N *CL "p# a# 8>> C4 : 6R* 0) 3> Days

S.N). Ti!"

2hs5

A+s)+. C)%c"%#a#i)% 2!(5 C!. &(

"l"as"

6 C!.

&( "l"as"!l : !l @>> !l

'. 0.$ 0.0' 0.0'4 0.01$ '$.5 '$.5 4.6$2. ' 0.'45 0.52 0.'6 21.1 21.11 '3.33

5. 2 0.253 0.035 0.22 51.4 51.$ '.34

3. 5 0.50$ 0.0$6 0.21 $0.3 $0.16 2$.35

$. 3 0.5$' 0.06$ 0.52 $1.$ $.23 2.62

6. $ 0.324 0.04 0.5 4'.' 42.'6 56.01

4. 6 0.3$4 0.013 0.32 4$.6 44.0$ 51.$5

1. 4 0.36 0.0' 0.3$ 1'.$ 12.44 3'.11

. 1 0.$6 0.'03 0.$2 5.$ $.3 34.43

'0. '0 0.64 0.'2$ 0.62 ''2.$ ''$.5$ $4.64

''. '2 0.404 0.'5 0.6$ ''4.0 '20.3' 60.23


8.1. PREFORMULATION PARAMETRS

8.1.1. S#&y )% D(

Ta+l" 8.1, R"sl#s a%& &iscssi)% )0 p"0)!la#i)% paa!"#"s )0 &(

S.N). Paa!"#"s R"sl#s C)%clsi)%

'. "hysical characters 7rystalline powder+ white+

Kdorless+ ;itter2. (dentification

"hysical method

%a& Lanthine test

%b& 8elting "oint

%c& oss on drying

%d& *ygroscopicity

Analytical method

%a& MmaD

"ositive

24007

0.5 B

0.04 B%room temp&

0.'6 B%30074$B)* &

240 nm %0.' 9 *7&

265 nm %0.'9 8ethanolic *7&

243 nm %0.' 9 9aK*5

Kn the bases of

these tests it

could be confirm

that the drug

sample was pure

and authentic.

Dept. of Pharmaceutical Sciences S.S.I.T.M.'''


50/65

Results

%b& ( ) spectra

%c& ) f%d& Assay

!howed all characteristics peaks

0.64

.'1$ B

5 !olubility Analysis

(n different solvents

%a& Fater

%b& 0.' 9 *7

%c& 0.' 9aK*

%d& Gthanol

(n different p*

%a& '.2 %0.'9 *7

%b& 5.$

%c& $

%d& 4

%e& 1

'20.1

54.5

20.

26.45

26.43 %mg ml5

25.4' %mg ml&

'4.0 2mg ml&

1.24 %mg ml&

'2.13 %mg ml&

!lightly soluble

!paringly soluble

!oluble

!lightly soluble

(ndicates

solubility slightly

increase as p*

increase+

otherwise it is

independent of

p*

3. 8icromeritics

%a& 7arrNs indeD

%b& Angle of repose

%c& *ausner )atio

24 B

5'0

'.56

"assable flow

$. "articles !ize )ange '0- '$0 micrometer ,ine and very

fine

6. "artition 7oefficient -0.666 %log p& (ndicates more

hydrophilicty

than lipohhilicity4. (onization 7onstant 1.4 and ''.34 (ndicates weak

acidic O weak

basic drug

1. rug "olymer (nteraction

!tudy

9o change in )f valve (ndicates no

interaction

8.1.. S#&y )% Psylli! *s

Ta+l" 8., R"sl#s a%& &iscssi)% )0 psylli! hs paa!"#"s

S.N). Paa!"#"s R"sl#s

*s psylli! D"hs psylli!

'. "hysical 7haracters "owder of psyllium

seed+ "ale buff color+

odorless+ Test less

"owder of psyllium

seed+ "ale buff color+

odorless+ Test less

2. Test for 8ucilaginous 8atter "ositive "ositive

5. p* %'B a=ueous !ol.& 6.1$ 6.1$

3. Ash


51/65

Results

$. GDtractive


52/65

Results

related to change in the porosity of the tablet. *owever as the porosity of the hydrated

matriD independent of initial porosity. Nih)&chi "# al.+ %'6& concluded the

compression force seem to have a little effect on the drug release.

All formulation was prepared with the help of "


53/65

Results

8..? Fl)a#i%( Capa+ili#i"s, - The floating capabilities mainly concern here with

floating lag time and floating duration.

The floating duration should be at least 23 hrs and the floating lag time should be as

low as possible because compleD anatomy and physiology of P(T. The fasted state is

associated with various cyclic movement commonly referred as !i(a#i%( !)#)

c)!pl"9 %887&.The third phase of 887 %burst phase& is characterize by the large+

intense and regular contraction termed as house keeper waves that swept out the

particulate matter %undigested food particles& from the stomach and lasts to '0to 20

minutes. To prevent the formulation from the effect of this phase+ tablet should be

float as fast as possible after reaching in the stomach.

(n similar way the floating duration and dimensional stability are important in case of

once daily formulation obtain the continuous and constant drug release up to the 23

hrs.

(f physical integrity of the formulation is note maintain+ the tablet could break down

in to the small fragments and escape from the upper part of P(T.

8..?.A E00"c# )0 Psylli! *s )% Fl)a#i%( Capa+ili#i"s, - The floating lag time

of formulation "' containing 200 mg of dehusk psyllium was 534#1.6 seconds.This formulation was not able to maintain the dimensional stability upto the re=uire

time %23 hrs& and duration of floating was ''.5#0.2$ hrs. As the concentration of the

dehusk psyllium increased from 200 to 300%': 2 drug: polymer ratio& the floating lag

time reduced to '02. # 2.$6 %batch "5& and floating duration and dimensional

stability both were maintained more than 23 hrs.

!imilar effect were observed with husk psyllium in similar ratio of the drug and

polymer but the floating log time was more than that of dehusk psyllium formulation.The floating lag time of formulation "5 containing 300 mg %':2 drug: polymer& of

husk psyllium was '20 # 2.$2 seconds as compared to dehusk psyllium formulation

"5 %'02. #2.$6 seconds&.

This was due to grater particle size of husk psyllium as compared to dehusk psyllium

which hydrate at the slow rate and take more time to swell. This result in increasing

the floating lags time.

Dept. of Pharmaceutical Sciences S.S.I.T.M.''$


54/65

Results

8..?.B E00"c# )0 S)& CMC )% Fl)a#i%( Capa+ili#i"s: -The !odium 787 was

added to reduce the floating lag time. ,ormulation containing $0 mg sodium 787

had the floating lag time 41 # '.5 and the formulation containing '00 mg of sodium

787 had 4'# 5. The reduction of the floating lag time is due to sodium 787 is a

synthetics agent which hydrated at a faster rate than that of psyllium husk.

!imilar effect was observed with husk psyllium powder. The floating lag time

containing husk psyllium along with $0 mg %batch "3& and '00 mg %batch "$& was

found to be 1$.4#$.05+ 4.5#'.$5 respectively.

There was no measurable effect of concentration !od 787 on floating duration and

dimensional stability.

8..?.C E00"c# )0 S)&i! Bica+)%a#" )% Fl)a#i%( Capa+ili#i"s, - The floating lag

time reduced as the concentration of sodium ;icarbonate increased in both cases i.e.

dehusk and husk formulations.

Ta+l" 8.3, E00"c# )0 s)& +ica+)%a#" )% 0l)a#i%( la( #i!"

S.N) C)%c. )0 s)&i!

+ica+)%a#"

265

D"hs 0)!la#i)% *s 0)!la#i)%F C F L T F C F L T

'. '0 "6 1#2.$' "6 '0$#$.2

2. '$ "3 41#'.5 "3 1$.4#$.05

5. 20 "4 60.4#2.$2 "4 6.4#2.01

,7 ,ormulation code+ ,T ,loating lag time

The concentrations of sodium ;icarbonate effect the duration of floating in both cases

i.e. dehusk and husk formulation. The duration of floating was 22#0.6'hrs %batch

"6& with '0 B sodium ;icarbonate and 23 hrs %batch "3+ "4& when the

concentration of sodium ;icarbonate 7as '$ B %batch "3& and 20 B.% batch "4&.

(n case of husk the duration of floating was 20.2#0.1$hrs %batch "6& with '0 B

sodium ;icarbonat" and 23 hrs when the concentration of sodium ;icarbonate was '$

B %batch "3& and 20 B.% batch " 4&.This might de due to the gas generated by '0 B

sodium ;icarbonate might not be sufficient to keep the formulation in floating state

for prolonged period of time %23 hrs& where as the in case of '$ B+ 20 B sodium



55/65

Results

;icarbonate sufficient gas produced to keep the formulation in floating state for 23

hrs.

The concentration of sodium ;icarbonate oppositely effect the dimensional stability

but this effect was not significant.

8..?.D E00"c# )0 Ac- Di S)l )% Fl)a#i%( Capa+ili#i"s, - Ac- i I!ol is a super

disintegrate when it come in contact with the medium swell rapidly at least two times

of its original volume. The psyllium husk and sodium ;icarbonate simultaneously

form the gel network due to which the swell mass of Ac-i-!ol is retaining in the gel

and tablet does note disintegrate.

The additional advantage of it+ the maDimum water uptake is achieved in short period

of time as the water reach in the deep in to the core of the tablet.

;eing a disintegrate Ac-i-!ol creates the pores and the 7K2 generated with the

reaction of !odium ;icarbonate and acidic medium was entrapped in the pores

resulting the floatation of the tablets i.e. the log time further reduced.

$ B and '0 B of Ac-i-!ol were used. The formulation containing '0 B Ac-i-!ol

%batch "72+ 3$# 2 seconds& take less time to float as compared to the formulation

containing $ B Ac-i-!ol %batch "7'+ $$.'# '.$5 seconds& in the case dehusk psyllium. !imilar effect was observed with formulation containing husk psyllium.

,ormulation containing *"87 C '00 8 showed very short lag time %batch *+ '0.5

#'.$5 seconds& without sod 787 and Ac-i-!ol.

8..?.E E00"c# )0 *a&%"ss )% Fl)a#i%( Capa+ili#i"s, - As the hardness increased

the floating lag time also increased. Kn immersion of tablets %batch "72+ "72+ * &

of hardness around 2 kg cm

2

in 0.' *7 solution floated immediately 3$.'#'.$5seconds for "72+ $0#'.65 seconds for "72+ zero for * & as compared to the

formulation 3 kg cm2 took more time % '0 # $ seconds for "72+ 200#1 seconds for

"72+'0.5 # '.$5 seconds *& to come up to the surface. The tablets hardness 6 kgcm2

showed the no floating in case of dehusk formulation and husk formulations while the

formulation containing *"87 ,loat in 0 # 4.$ seconds.

(n fact+ buoyancy of the tablet is governed by both the swelling the outer surface of

the tablets when it comes in the contact with the gastric fluids+ and the presence of the



56/65

Results

internal void %"orosity& in the dry centre of the tablet. These two factors are essential

for the tablet to ac=uire bulk density less than that of the gastric fluid i.e. '.03 gmcm 5

which helps them to remain buoyant on gastric fluids %sheth and tossoumnian+ '4&

7ompression force of these tablets to high degree hardness may result in reduction of

porosity of the tablets and moreover+ the compressed hydrocolloids particle on the

surface of the tablets fail to hydrate rapidly when the tablets come in to contact with

the gastric fluid+ and as a result of this+ the capability of the tablets to float is

significantly reduced.

8.. D"%si#y, - The density of the formulation should be less than that of '.03

kgcm5

%7hues et. al. '0&.

The density of all the formulation was in the range of 0.42 # 0.01$ to '.034 # 0.023

for all formulation.

8.. S7"lli%( I%&"9, - ;aumgartner et al. 2'1& 7oncluded that tablets composed

of polymeric matrices build a gel layer around the tablet core when they come in

contact with water This gel govern the drug release. Cinetics of swelling is important

because the gel barrier is formed with water penetration. !welling is a vital factor toensure floating. To obtain floating+ the balance between the swelling and water must

be reported.

As shown in table the formulation containing psyllium husk %both grades dehusk and

husk psylluim& took about 6 to 1 hrs to complete swell as compared to the formulation

prepared with *"87 k'00 8 that took 3-$ hrs to complete swell.

(n the first hr of study+ the swelling indeD of formulation "5 was $4.' B %dehusk

psyllium&+ "5 was 36.05 B %husk psyllium&+ and * was 1$.2 B %*"87 C '00 8&The difference in the swelling indeD was because of the psyllium husk is a natural

agent took more time to hydrate as compared to synthetic agent *"87 C '00 8.

The difference in the swelling indeD between the formulation prepared with husk and

dehusk psyllium was due to the difference in the particle size. The particle size of

husk psyllium powder was grater than that of the dehusk psyllium resulting the

delayed the hydration.



57/65

Results

After complete swelling the formulation prepared with husk psyllium %"5 531.'$ B&

showed the grater-swelling indeD than that of dehusk psyllium %;atch "5+ 553. B&+

this was due to presence of husk in husk psyllium+ which enhance the swelling indeD.

Addition of !od .787 enhanced the swelling indeD at initial stage %batch "3 40.

B+ batch "3 $1.B& due to faster rate of hydration as compared to psyllium powder.

The formulation prepared with sod .787 and Ac- i I!ol showed the swelling indeD

after first hr of study was 41.'3 B %batch "72&+ 6$.'2 B %batch "72& due to he

grater efficiency Ac- i I!ol for water and faster hydration.

8..@ E)si)% S#&y, -The tablets containing the husk psyllium showed the higher

erosion after '2 hrs %.2$B batch "5& than that of formulation prepared with dehusk psyllium %4.3B batch "5&. Addition of !od 787 reduced the erosion in both

formulation prepared with husk %6.4 B batch "3& and dehusk psylluim %$.14 B batch

"3&.

,ormulation containing Ac-i-!ol further reduced the percent erosion %3.$ B "72+

$.0' B batch "72& than that of formulation prepared with psyllium alone %4.3B

batch "5 .2$B batch "5& or in combination with sod 787 %$.14 B batch "3+

6.4 B batch "3&

The formulation containing pure *"87 C '00 8 showed the lowest erosion among

all the preparation.

8..1> In-Vitro R"l"as" S#&y

8..1>.A E00"c# )0 Psylli! *s )% In-Vitro R"l"as": - The formulation "'

%dehusk psylluim& and "'%husk psyllium& %200 mg psyllium husk+ ':' drug :polymer&

the burst release after 2 hrs was 55$.$'and 54.2 and final release after '2 hrs was

12.22 and 10.42 respectively. ;ut these formulations were not able to maintain the

dimensional stability and the drug release was note up to 23 hrs. !o the amount of

psyllium was increased to 500mg %':'.$ drug: polymer& and 300 mg %':2+ drug:

polymer&. The burst release after 2 hrs was 23.' %"2&+ 2.5 %"2& for the

formulation containing 500 mg of psyllium husk and 20.4 %"5&+ 2$.32 %"5& for the

formulation containing 300 mg of psyllium husk. ,inal B cumulative drug release

after '2 hrs 66.25 %"2&+ $4.$6 %"2& for the formulation containing 500 mg of

psyllium husk. and 34.1 %"5& and 3.$1 %"5& for the formulation containing 300 mg

Dept. of Pharmaceutical Sciences S.S.I.T.M.''


58/65

Results

of psyllium husk. This might be due to gelling property of psyllium husk. As the

concentration of psyllium husk incased resulting in increased the gel concentration+

which lead to increased the diffusion pathway and thus decreased the diffusion rate+

which decreased the release of the drug+ and complete release was obtained in 23 hrs.The burst release of formulation prepared with hush psyllium was slightly more than

that of dehusk .(t was due to larger particle size of husk psyllium than that of dehusk

psyllium which took more time to hydrate than that of dehusk.

The total B cumulative drug release after '2 hrs from dehusk psyllium formulation

was slightly more than that of husk psyllium formulation. (t was due to the presence

of husk in hush psyllium+ which provides an additive effect in swelling resulting

slightly reduction in drug release.

2A5 *s psylli!



59/65

Results

2B5 D"hs psylli!

Fi( 8.1, E00"c# )0 psylli! hs )% In- vitro &( "l"as"

8..1>.B E00"c# )0 S)&i! CMC )% In-Vitro R"l"as", - Two =uantity of the

sodium 787 %$0 O'00 mg& were used in both grades of psyllum husk.

There was no significant effect on the drug release but the burst release after 2 hrs was

reduced. The reason behind it faster rate of hydration of sodium 787 than psyllium

husk..

The B burst release of after 2 hrs for formulation containing sodium 787 was 20.'3

%batch "3+ dehusk psylluim&+ 22.40 %batch "3+ husk psyllium& than that of the

formulation with out sodium 787 22.4 %batch "5& and 2$.32 %batch "5&.

Dept. of Pharmaceutical Sciences S.S.I.T.M.'2'


60/65

Results

0

10

20

30

40

50

60

0 5 10 15Time (hrs)

% C u m . D r u

g r e l e a s e P3

P4

P5

2A5 *s psylli!

0

10

20

30

40

50

60

0 5 10 15

Time(hrs)

%

C u m .

D r u g r e l e a s e

DP3

DP4

DP5

2B5 D"hs psylli!

Fi( 8., E00"c# )0 S)&. CMC )% in- vitro &( "l"as"

8..1>.C R"l"as" 0)! #h" F)!la#i)% C)%#ai%i%( *PMC 1>> M, - Tocompare the release pattern of the psylluim %both grades&+ separate formulation

containing *"87 C '00 8 was prepared in ': 2 ratio of drug and polymer.

The initial B burst release after 2 hrs with *"87 C'00 8 was '.$2 %batch *& which

was less than that of preparation prepared with psyllium powder %batch "3 -20.'3

batch "3- 22.4&. The B cumulative drug release after '2 hrs was $.34 # %batch *&+

3.34 %batch "3& and 36.1 %batch "3&.



61/65

Results

(nitial burst release in case of *"87 C'00 8 was low than that of psyllium due to

faster rate of swelling of *"87 C'00 8. After '2 hrs release of drug from *"87

was more than that of formulation prepared with psyllium because the swelling indeD

of psyllium was more than that of *"87 C'00 8.

Fi( 8.3, Gffect of *"87 C '00 8 on in- vitro drug release

8..1>.D E00"c# )0 C)ss P)/i&)%" )% In-Vitro R"l"as", - In order to improve the

release profile of formulation prepared with psyllum husk as parallel to *"87 C'00

8 the cross povidone was used.

,ormulation containing 0 B of Ac-i-!ol showed the cumulative B drug release

3.34 %batch "3&+ 36.1 %batch "3& and formulation containing $B Ac-i-!ol

showed the cumulative B drug release was $$.24 %batch 7"'&+ $2.03 %batch "7'&.

,ormulation containing '0B Ac-i-!ol showed the cumulative B drug release was

60.0' %batch 7"2&+ $1. '$ %batch "72& which was comparable to formulation

prepared with *"87 C '00 8 %batch *+ $.34&.

The reason behind it Ac-i-!ol is a super disintegrate and creates pores in the net

work form by psyllium and sod.787.due to which the release of the drug increased

in the latter hrs.



62/65

Results

0

10

20

3040

50

60

70

0 5 10 15Time(hrs)

%

C u m .

D r u g

r e l e a s e

P4PC1PC2

2A5*s psylli!

0

10

20

30

40

50

60

70

0 5 10 15Time(hrs)

% C u m D r u g r e l e a s e

DP4DPC1DPC2

2B5 D"hs psylli!

Fi( 8.8: E00"c# )0 Ac-Di-S)l )% in- vitro &( "l"as"

8..1>.E E00"c# )0 S)& Bica+)%a#" )% In-Vitro R"l"as", - !odium bicarbonateshowed the opposite effect on percentage cumulative drug release. This might be due

to the alkaline nature of the sodium bicarbonate+ which create an alkaline environment

around the tablet. Theophylline was less soluble in the alkaline environment that

decreased the release of drug from the formulation. ,ormulation containing '0 B

9a*7K5 shown the drug release after '2 hrs was $'.32 %batch "6&+ 31.5 %batch

"6& as compared to formulation 20 B 9a*7K5 the drug release after '2 hrs was

34.44 %batch "4&+ 3$.$$ %batch "4&



63/65

Results

2A5 *s psylli!

2B5 D"hs psylli!

Fi( 8.:, E00"c# )0 s)&. +ica+)%a#" )% in- vitro &( "l"as"

8..1>.F E00"c# )0 A(i#a#i)% )% I%-/i#) D( R"l"as", -This study was conducted

only on optimized formulation like "72 %dehusk&+ "72 %husk&+ * %*"87 C '008&.

At $0 rpm cumulative percentage drug release after '2 hrs was formed to be $4.26

%"72&+ $6.4' %"72&+ $1.2' %*&.

At '00 rpm cumulative percentage drug release after '2 hrs was 60.0' # 0. %"72&+

$1.'$ %"72&+ $.34 %*&.

The release of drug was slightly higher at '00 rpm+ since the delivery by diffusion

mechanism occurred through the gel layer+ the system is mainly based on this release

mechanism get effected by stirring.%,(P. 3.6&

Dept. of Pharmaceutical Sciences S.S.I.T.M.'2$


64/65

Results

2A5 DPC

2B5 PC

2C5 *

Fi( 8.?, E00"c# )0 RPM )% in- vitro &( "l"as"

8..11. R"l"as" i%"#ics, - The In-vitro release data of optimized formulations were

treated with different kinetics models to eDplain the release kinetics of theophylline

from floating matriD tablets. These models were zero order+ first order+ higuchi model+

hiDon-crowel model and korsemayer peppas model. *iguchi model was considered as

the best fitted model with the highest value of correlation coefficient %r2&. The value



65/65

Results

r2 of different optimized formulation "72+ "72+ * were found to be 0.4+ 0.0'+

and 0.' respectively.

The release data were further treated by )itger-"eppas or power law to calculate the

value of n %release eDponent&. The values of n %release eDponent& for different

optimized formulations were found to be 0.$322 for "72 %dehusk psyllium&+ 0.$'36

for "72 %husk psyllium&+ and 0.6331 for *%*"87 C '00 8&. The value of n indicate

that the release mechanism from different formulation was the non-fickian diffusion

%anomalous type&+ controlled by the diffusion through swollen matriD.

8..1. D( P)ly!" I%#"ac#i)% S#&y )% Op#i!i$"& F)!la#i)%: - rug and

polymer interaction in the optimized formulation was checked with the help of T7

and ,T-() study.

T7 data showed that there was not a significance difference in the ) f value. ,T-()

data also showed that the characteristics peaks of drug of were observed in the ,T-()

!pectra of formulation prepared with "syllium husk %"72 O "72& and *"87 C

'00 8.

8..13. S#a#is#ical A%alysis, - Analysis of variance %A9K

Documents

Result and Discussion 6