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SALIENT FEATURES: INTRODUCTIONAIMS AND OBJECTIVESLITERATURE REVIEW
PROFILE OF DRUGLIST OF MATERIALS ANDEQUIPMENTS
EXPERIMENTAL WORK RESULT AND DISCUSSIONSUMMARY AND CONCLUSION
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FUROSEMIDE
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LOOP DIURETICAGENT
USED ORALLY IN THETREATMENT OFEDEMATOUS STATES
ASSOCIATED WITHCARDIAC, RENAL, ANDHEPATIC FAILURE ANDTHE TREATMENT OFHYPERTENSION.
IT IS A BCSCLASS IVDRUG
ATTEMPTS HAVE BEENMADE TO DEVELOPSYSTEMS WHICHINCREASE BOTH THESOLUBILITY ANDPERMEABILITY OFFUROSEMIDE.
FUROSEMIDE HASLOW
PERMEABILITYAND SOLUBILITY
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HYPOTHESISIt ! "#$%t"&! '&( t")t ) *+ %)("&! -& /0 %
+1%!&0 (& 2 // "&/$ 3 0$1%- 34 * %)-) /)* / t#55 A-% ()3 & % 1!t $)!! 0&t)*%/ !05T"1%+4" 3 %1$%1)t %3 % "&0 )/ $&10&)t %3
&3")3 &15T"1%+4" 0$1%- 34 t"& ( !!%/+t %3 *#
%0$/&6)t %3 2 t" "#(1%6#$1%$#/787 # /%(&6t1 3
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AIMS
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OBJECTIVEST% $1&$)1& 3 /+! %3 %0$/&6 % +1%!&0 (&.T% (&-&/%$ ) *+ %)("&! -& /0 (%!)4& %10 %1
+1%!&0 (&.
T% &-)/+)t& t"& *+ %)("&! -& /0 %1 $&10&)t %3&3")3 &0&3t - ) t1)3!*+ )/ 1%+t&.T% !t+(# t"& & & t % "&0 )/ $&10&)t %3 &3")3 &1 %3t"& * %)-) /)* / t# &3")3 &0&3t % +1%!&0 (& - )
t1)3!*+ )/ 1%+t&.T% !t+(# t"& & & t % 3 /+! %3 %0$/&6 % +1%!&0 (&%3 t"& * %)-) /)* / t# &3")3 &0&3t % +1%!&0 (& - )t1)3!*+ )/ 1%+t&.
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LITERATURE REVIEW
18.5.11 correction\W CORR\3. Literature review.docx18.5.11 correction\W CORR\R ! R"C #.docx
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http://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/3.%20Literature%20review.docxhttp://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/3.%20Literature%20review.docxhttp://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/REFERNCES.docxhttp://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/REFERNCES.docxhttp://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/3.%20Literature%20review.docxhttp://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/3.%20Literature%20review.docxhttp://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/REFERNCES.docxhttp://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/3.%20Literature%20review.docxhttp://var/www/apps/conversion/tmp/scratch_4/18.5.11%20correction/W%20CORR/3.%20Literature%20review.docx
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PROFILE OF DRUGG&3&1 N)0& )3( A(( t %3)/ N)0&:F+1%!&0 (& 9 F1+!&0 (&E0$&1 )/ %10+/): C ; H C/N ; O
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BIOPHARMACEUTICSDATA
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PHARMACOKINETIC DATA
HALF LIFE 2 %our& '30(120 )in *
PROTEIN BINDING $5 + ',L- "*
ABSORPTION WINDOW R
METABOLISM R ! R# ,## !! C
BIOAVAILABILITY 60 70+ ' RR, C*
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LIST OF MATERIALS
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S1. N% M)t&1 )/ S+$$/ &1! 9 M)3+ ) t+1&1!F+1%!&0 (& @4 t !)0$/& S)3% )-&3t !, A3 /&!"2)1
; C" t%!)3 H 0&( ) L)*%1)t%1 &! P-t. Lt(., M+0*) @I3( )
= Et"#/ &//+/%!& L%*) "&0 &, M+0*) , I3( )
PVP K => @$%/# - 3#/ $#1%// (%3& H 0&( ) L)*%1)t%1 &! P-t. Lt(., M+0*) @I3( )
< S%( +0 4/# % "%/)t& H 0&( ) L)*%1)t%1 &! P-t. Lt(., M+0*) @I3( )
A &t%3& S+/)* R&)4&3t!, S+- (" 3)t" L)*%1)t%1 &!, B)1%()
@I3( )
? A &t A ( M&1 , I3( )
A*!%/+t& )/ %"%/ S"1&& C")/t")3 V *")4 K")3( U(#%4 S)") )1
M)3(/ Lt(., S+1)t @I3( )
P%t)!! +0 ( "#(1%4&3 $"%!$")t& L%*) "&0 &, M+0*) , I3( )
> S%( +0 "#(1%6 (& L%*) "&0 &, M+0*) , I3( )
S%( +0 "/%1 (& L%*) "&0 &, M+0*) , I3( )
; C)/ +0 "/%1 (& L%*) "&0 &, M+0*) , I3( )
5A// %t"&1 1&)4&3t! )3( "&0 )/! +!&( 2&1& % /)*%1)t%1# 41)(&.
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LIST OF EQUIPMENTS
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S1. N% E + $0&3t! M%(&/9 M)3+ ) t+1&1!M)43&t !t 11&1 MS7> R&0 3!t1+0&3t! Lt(. @I3( )
; D 4 t)/ *)/)3 & ELB=>> S" 0)('+, J)$)3
= T1)# (1#&1 DTC =>= R ((" T1)( 34 C%0$)3#, A"0&()*)(,
I3( )P1%$&//&1 !t 11&1 RQ ;; R&0 I3!t1+0&3t! Lt(. @I3( )
< UV !$& t1%$"%t%0&t&1 UV7 ?>> S" 0)('+, J)$)3
FTIR @ %+1 &1 t1)3! %10&( 3 1)1&(
!$& t1%0&t&1
NICHOLET ?>>, T"&10% S &3t @G&10)3#
? X 1)# ( 1) t%0&t&1 D; P")!&1, B1+ &1 AXS I3 . @G&10)3#
D 1&3t )/ ! )33 34 )/%1 0&t1# P#1 ! DSC, P&1 3E/0&1, USA
T&6t+1& )3)/#!&1 B1%% & &/( QTS7;
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QUIC
KOVERVIE
W11/20/15 13
EXPERIMENTAL WORK
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PRELIMINARYEXPERIMENTS
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D1+4C")1) t&1 ')t %3
FTIR
MAX 3 W)t&1,Et")3%/
>. N N)OH
MELTINGPOINT
; 7;;; > C
;; 30,;? 30,==> 30
100
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4 3 2
. 0 1
4 9 5
. 0 5
5 3 6
. 7 9
5 8 1
. 6 6
6 1 9
. 3 6 6
5 1
. 3 9
6
8 6
. 7 4
7 0 8
. 3 5
7 4 3
. 6 5
7 8 9
. 7 7
8 4 6
. 8 3
9 1 9
. 3 0
9 4 4
. 2 5
9 7 9
. 3 3
1 0 1 5
. 2 9
1 0 5 3
. 5 0
1 0 7 2
. 6 0
1 1 4 3
. 2 1
1 2 4 1
. 1 7
1 2 6 5
. 5 2
1 3 2 3
. 7 0
1 3 5 3
. 7 6 1
4 0 9
. 7 2
1 4 4 5
. 7 5
1 4 9 1
. 2 0
1 5 6 4
. 4 8
1 5 9 2
. 8 8
1 6 7 2
. 7 8
2 5 5 6
. 4 9
2 9 6 0
. 5 0
3 1 1 8
. 9 8
3 2 8 4
. 0 3
3 3 5 1
. 4 6
3 3 9 8
. 8 8
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
40
50
60
70
80
90
100
% T
5001000150020002500300035004000
cm-1
F+3 t %3)/ G1%+$ R&$%1t&( F1& +&3 &! @ 07 O*!&1-&( F1& +&3 &! @ 07
NH !t1&t " % C7NH 41%+$ ==7= >> ==< .
C O !t1&t " % COOH 41%+$ ? ?;.?
NH !t1&t " % NH ; 41%+$ < < ;.
7S O !t1&t " % SO; 41%+$ =;; =;=.?>
C/ !t1&t " % C7C/ 41%+$ < ; < .
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• C)/ *1)t %3 +1-&)t $H .; )3( ?.
$H .;
$H ?.C
S 0+/)t&( !)/ -)1# /+ (@ . =; 40 KH ; PO , ;.=40 % N)C/ )3( >. ;
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PREPARATION OFINCLUSION COMPLEX
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QUICKOVERVIEW
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PHASE SOLUBILITY STUDY
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>.>= >.>
>.>> >.>;
>.><
INCUBATOR SHAKER
RPM TEMP: =? ; > C
D &1&3t 0M %3 &3t1)t %3 % HP787CD !%/+t %3 < 0/ 2 t" &6 &!! % (1+4
04
F /t1)t&
>.;;/t&1
UV)3)/#! !)t ;;
30
C)/ +/)t& K S @!t)* / t#
%3!t)3t )3( CE@ %0$/&6)t %3
& &3 #
T 0&:; "%+1!
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PREPARATION OFINCLUSION COMPLEX
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. F)1 )!, A. J)11%+6, N. F)1 )!, A.7M. H)1)*)4 +., V. G+&4)3, P., S#3t"&! ! )3( ")1) t&1 ')t %3 %+1%!&0 (& %0$/&6 3 87C# /%(&6t1 3. D 4&!t J%+13)/ % N)3%0)t&1 )/! )3( B %!t1+ t+1&! ;>> , @; ,
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D1+4 !%/+t %3A &t%3&
?> >C
P1& $ t)t&!
COOLING
CYCLODEXTRINSOLUTION
D !t //&( 2)t&1
EVALUATIONOF INCLUSION
COMPLEX
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RESULTS AND DISCUSSION
RATIONALE FOR SELECTION OFEXCIPIENTS
HP787CD @"#(1%6#$1%$#/7*&t)7 # /%(&6t1 3 "on toxic at ow to )oderate ora andintravenou& do&e& a& indicated 9-rew&ter et a 1
ore water &o u e t%an t%e natura :c9c odextrin
PHASE SOLUBILITY STUDY :K S =>.> M 7: )3( CE >.
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DSC THERMOGRAPH OFFUROSEMIDE
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FIGURE7DSC THERMOGRAPH OF FUROSEMIDE
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DSC OVERLAY THERMOGRAPH
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F 4+1&7 O-&1/)# DSC t"&10%41)$"! % ) F+1%!&0 (& * HP787CD $"#! )/ 0 6t+1& % +1%!&0 (&: HP787CD @ : .< ( +1%!&0 (&: HP787CD
%0$/&6 @ : .<
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FTIR OVERLAY SPECTRA
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F 4+1&: FTIR !$& t1) %1 @) +1%!&0 (& @* HP787CD @ $"#! )/ 0 6t+1&% +1%!&0 (&: HP787CD @ : .< @( 3 /+! %3 %0$/&6 +1%!&0 (&: HP787CD@ : .<
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XRD DIFFRACTOMETRY
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F 4+1&: X 1)# ( 1) t%41)0! % @) +1%!&0 (& @* HP787CD @ t"&$"#! )/ 0 6t+1& @ : .< (1+4: HP787CD )3( @( 3 /+! %3 %0$/&6 @ : .<(1+4: HP787CD
S 0 /)1 1&!+/t! 2&1& %+3( *# S$)0&1 &t )/ %1 %0$/&6)t %3 % +1%!&0 (& 2 t" HP787CD.. S$)0&1, E. M //&1, D. G. W&!!&/!, P. L. V&3t&1, J. P., C")1) t&1 ')t %3 % t"& %0$/&6&! % +1%!&0 (& 2 t" ;7"#(1%6#$1%$#/7*&t) 7 # /%(&6t1 3 )3( !+/ %*+t#/ &t"&17?7 *&t) 7 # /%(&6t1 3. E+1%$&)3 J%+13)/ O P")10) &+t )/ S &3 &! ;>>;, @ 7< , ; ?7;
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IN VITRO DISSOLUTION PROFILE
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MEDIUM: $H ?. *+ &1 M&t"%(: USP A$$)1)t+! II @$)((/& V%/+0&% D !!%/+t %3 : >> 0L T&0$&1)t+1&: =? ; >C RPM:
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SUMMARYH#(1%6#$1%$#/787 # /%(&6t1 3 ")! *&tt&1 !%/+* / ' 34$1%$&1t#.P")!& !%/+* / t# !t+(# 2)! $&1 %10&( t% 3%2 t"&!t% " %0&t1 $1%$%1t %3! % +1%!&0 (& )3( HP787
CD )3( t% 3%2 !t)* / t# %3!t)3t % t"&%0$/&6)t %3 $1% &!!.
C%0$/&6)t %3 & &3 # 2)! )/!% &-)/+)t&(.I3 /+! %3 %0$/&6 3 0%/)1 1)t % % : .< 2)!
$1&$)1&( +! 34 %7$1& $ t)t %3 0&t"%(.I3 /+! %3 %0$/&6 2)! &-)/+)t&( +! 34 DSC, FTIR,XRD )3( 3 - t1% ( !!%/+t %3 !t+(#.
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CONCLUSIONI3 %3 /+! %3, t"& %10)t %3 % 3 /+! %3 %0$/&6 ! )4%%( )$$1%) " %1 &3")3 &0&3t % !%/+* / t# %
+1%!&0 (&.T"& %10)t %3 % 3 /+! %3 %0$/&6 )3 *& &-)/+)t&(
+1t"&1 +! 34 SEM @! )33 34 3 /+! %3 0 1%! %$# ,H7 NMR @3+ /&)1 0)43&t 1&!%3)3 & t% 4&t
%0$/&t& 3 %10)t %3 )*%+t t"& %0$/&6 %10&(.A/!%, ( &1&3t 0&t"%(! %1 %10)t %3 % 3 /+! %3
%0$/&6 )3 *& &6$/%1&(.T"%+4" 1&&'& (1# 34 % t"& 3)/ $1%(+ t ! )3&6$&3! -& 0&t"%( t )3 *& ) 4%%( )/t&13)t -& t% 4&t*&tt&1 3 /+! %3 %0$/&6 $1%(+ t.
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DEVELOPMENT OFBUCCOADHESIVE FILMS
OF FUROSEMIDE
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QUICKOVERVIEW
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11/20/15 33
PREPARATION OFMUCOADHESIVE
LAYER
PVP K=>
CHITOSAN
GLYCEROL
SGC
R O OR#
DRUGSOLUTION
<
=
;
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11/20/15 34
MIXTURE
PETRY DISH
TRAYDRYER
DRIED FILMS
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PREPARATIONOF BACKING
LAYER ETHYLCELLULOSE =>>04>.< 0L GLYCERINE
ACETONE
PETRI DISH
AIR DRYING
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EXPERIMENTAL DESIGN
A ; ; ) t%1 )/ (&! 43 2)! &0$/%#&( t% !t+(#t"& & & t % ; 3(&$&3(&3t -)1 )*/&! )t ;/&-&/!. I3(&$&3(&3t -)1 )*/&!: %3 &3t1)t %3
% $&10&)t %3 &3")3 &1 @SGC )3(%3 &3t1)t %3 % " t%!)3 )3( (&$&3(&3t
-)1 )*/&: !t&)(# !t)t& /+6 J SS .
T)*/& 3( )t&( t"& ) t+)/ -)/+&! )3( %(&(9t1)3! %10&( -)/+&! % 3(&$&3(&3t -)1 )*/&!.
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I3(&$&3(&3t V)1 )*/&! L&-&/!
C%(&( V)/+&! A t+)/ V)/+&!
@
C%3 &3t1)t %3 % " t%!)3 @ 5 6 7
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11/20/15 38
B)t " %(&
L&-&/!
C%(&( -)/+&! A t+)/ -)/+&!
C" t%!)3
6
SGC
6 ;
C" t%!)3
6
SGC
6 ;P 7 <
P ; < <P = 7 7 > 04W& 4"t % " t%!)3 %1 )3( 7 /&-&/, < > 04 )3( ; ==> 04W& 4"t % !%( +0 4/# % "%/)t& %1 7 )3( /&-&/, ( < 04 )3( ( ; => 04W& 4"t % PVP K=>, * )7 )3( * ; )7 ;
2& 4"t % " t%!)3 >> 9 ) )3( ; >> 9 ) 2& 4"t % !%( +0 4/# % "%/)t& ( >> 9 ) )3( ( ; >> 9 )
555R&!t )// $)1)0&t&1! % %10+/)t %3 2&1& &$t %3!t)3t - '. -%/+0& % >.< ) &t ) ( ;< 0/ -%/+0& %4/# &1 3& >.< 0/ -%/+0& % &t")3%/ < 0/ !t 11 34 !$&&( % $1%$&//&1 !t 11&1 ? 1$0 ( )0&t&1 % P&t1 ( !" ?>7
?; 00.
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IN VITRO PERMEATIONSTUDY
D%3& +! 34 %- 3& *+ )/ 0+ %!) @!"&&$,ovis aeries .A 0+ %!) 0&0*1)3& t")t )3 %-&1 )3 )1&) )*%-& ;.< 0 ; 2)! +t)3( !+$$%1t&( %3 ( )/#! ! 0&0*1)3&!, 2" " 2)! )$$/ &( %3 t"&1& &$t%1 ")0*&1 % ) F1)3' ( +! %3 &//.B+ %)("&! -& * /)#&1 /0 2)! )$$/ &( %3 t"& 0+ %!), 3 !+ " ) 2)#t")t t"& 0+ %)("&! -& /)#&1 ) 34 t"& 0+ %!)/ !+1 ) &.
0/ % ! 0+/)t&( !)/ -)1# /+ (, $H .; 2)! //&( 3 t"& (%3%1")0*&1 )3( !%t%3 $"%!$")t& *+ &1 $H ?. 2)! +!&( 3 t"&
1& &$t%1 ")0*&1.
At 1&4+/)1 t 0& 3t&1-)/ % , , > )3( ;> 0 3+t&! )3( t"&3&-&1# "%+1 +$ t% "%+1! ;>> L !)0$/& 2)! 2 t"(1)23 1%0 t"&1& &$t%1 ")0*&1 )3( 1&$/) &( *# !%t%3 $"%!$")t& *+ &1 $H ?. .T"& !)0$/&! 2&1& )!!)#&( *# t"& UV !$& t1%$"%t%0&t&1 )t ;; 30.
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CALCULATION OF STEADY STATE FLUX@JSS AND ENHANCEMENT RATIO
T"& )0%+3t % (1+4 $1&!&3t 3 t"& 1& &$t%1 %0$)1t0&3t2)! (&t&10 3&( )3( $/%tt&( )! ) +3 t %3 % t 0&. T"&$&10&)* / t# %& &3t! @P 2&1& )/ +/)t&( 1%0 t"&/ 3&)1 $)1t % t"& +1-&! )! %//%2! @M)!"1+ &t )/ ; :
P @(Q 9 (T 9A5 C( – W"&1&, A t"& !+1 ) & )1&) % ( +! %3 0; , (Q9(t
J!! !t&)(# !t)t& /+6 )0%+3t % (1+4 $&10&)t&($&1 +3 t t 0& )t !t&)(# !t)t&, )3( C( (1+4
%3 &3t1)t %3 3 t"& (%3%1 !%/+t %3.H&1&, )! +1%!&0 (& ! )3 ) ( (1+4, ")- 34 $K) -)/+& %=. t 1&0) 3! 3 %3 '&( %10 3 t"& $H ?. .S%, t1)3!$%1t % +1%!&0 (& ! )!!+0&( t% *& - ) $)1)7
&//+/)1 $)t" )3( !% t"& !t&)(# !t)t& /+6 %1 $)1) &//)1$)t" ! %3! (&1&(. J !! P 5 C( @M)!"1+ &t )/ ; .
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ENHANCEMENT RATIOT"& $&10&)* / t# % +1%!&0 (& 3 $1&!&3 & % !%( +0 4/# % "%/)t&2)! &-)/+)t&( *# &3")3 &0&3t 1)t %. It 2)! )/ +/)t&( )! @S"% )& &t)/ = :E3 ")3 &0&3t R)t % P !4 9 P +1
–
W"&1&, PSGC P&10&)* / t# %& &3t 3 $1&!&3 & % SGC )3(P FUR P&10&)* / t# %& &3t 3 )*!&3 & % )3# $&10&)t %3&3")3 &1 .
11/20/15 41
. P)t&/, V. P1) )$)t , B. P)t&/, M., D&! 43 )3( ")1) t&1 ')t %3 % " t%!)37 %3t) 3 340+ %)("&! -& *+ )/ $)t "&! % $1%$1)3%/%/ "#(1% "/%1 (&. A t) P")10) &+t ) ;>>?,
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EVALUATION OF FILM. P"#! )/ ")1) t&1 ')t %3 t" 3&!! )3( %/( 34 &3(+1)3 &
;. S2&// 34 3(&6 )3( S+1 ) & $H
=. M& ")3 )/ $1%$&1t &!7 T&3! /& !t1&34t" )3( &/%34)t %3 )t *1&) ;
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11/20/15 45B1%% & &/( T&6t+1& A3)/#!&1 %1 t&3! /& !t1&34t" !t+(#
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11/20/15 46
A!!&0*/# %1 0+ %)("&! %3 !t+(#
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RATIONALE FOR SELECTION OF EXCIPIENTS
C" t%!)3 : – * %(&41)()*/&, 3)t+1)/ $%/#0&1, 3%3 t%6 )3(
0+ %)("&! -&, * % %0$)t */& )3( )t %3 $%/#0&1. – &6 &//&3t 4&/ %10 34 )3( /0 %10 34 $1%$&1t &! !% t ! )
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. S&3&/, S. K1&0&1, M. J. K), S. W&1t', P. W. H 3 )/, A. A. S + &1, C. A., E3")3 34& & t % " t%!)3 %3 $&$t (& (1+4 (&/ -&1# ) 1%!! *+ )/ 0+ %!). B %0)t&1 )/! ;>>>, ; @;> ,;> ?;. S)/)0)t7M //&1, N. C" tt ")34, M. J%"3!t%3, T. P., T"& +!& % 0+ %)("&! -& $%/#0&1! 3*+ )/ (1+4 (&/ -&1#. A(-)3 &( D1+4 D&/ -&1# R&- &2! ;>>
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SELECTION OF BLEND OFPOLYMERS
O-&1 "#(1)t %3 % " t%!)3 0)# /&)( t% !/ $$&1# 0+ /)4&.S%, t% )-% ( 0+ %)("&! %3 ) /+1& %t"&1 $%/#0&1! )1&)((&( t% t"& /0!. :
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. E/7K)0&/, A. A!"1 , L. A/!)11), I., M 1%0)t1 )/ 0&t1%3 ()'%/& *&3'%)t& /0 )! )/% )/ 0+ %)("&! -& (&/ -&1# !#!t&0 %1 t1&)t0&3t % $&1 %(%3t)/ ( !&)!&!. AAPSP")10S T& " ;>>?, @= , E 7E .;. P)t&/, V. P1) )$)t , B. P)t&/, M., E & t % "#(1%$" / $%/#0&1! %3 *+ %)("&! -&&+(1)4 t $)t "&! % $1%$1)3%/%/ "#(1% "/%1 (& +! 34 ) t%1 )/ (&! 43. AAPS P")10S T& ";>>?, @; , E 7E ; .
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SELECTION OF PERMEATION ENHANCERAND BACKING LAYER POLYMER
V)1 %+! /)!!&! % "&0 )/$&10&)t %3 &3")3 &1! )1& +!&(/ & * /& !)/t!, t&1$&3&!, " t%!)3,
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STEPS FOR IDENTIFICATION OF FORMULATION
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PHYSICAL CHARACTERIZATION
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-atc% code
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FORMULATION OPTIMIZATION: ; ; FULL FACTORIAL DESIGN
T"& %$t 0 '&( *)t " 2)! !&/& t&( @P ; %3 t"& *)! ! %" 4"&1 J SS .
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. M)!"1+, R. C. S+t)1 #), V. B. S)3 )/ ), M. G. S)3 )/ ), J. M., E & t % $H%3 I3 V t1% P&10&)t %3 % O3()3!&t1%3 H#(1% "/%1 (& A 1%!! P%1 3& B+ )/M+ %!). P")10 D&- T& "3%/ ;>> @; , ; 7; ?.
T)*/& : St&)(# !t)t& /+6 )3( $&10&)* / t# %& &3t! )3( &3")3 &0&3t 1)t %
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11/20/15 53
T) /& : St&)(# !t)t& /+6 )3( $&10&) / t# %& &3t! )3( &3 )3 &0&3t 1)t %% B /)#&1 /0! @3 =
B)t " %(&
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57 )3( /&-&/! % 6 3( )t&
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11/20/15 54
%e &tati&tica ana 9&i& data t%rou>% re>re&&ion )ode i& .>>>
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RESPONSE SURFACE PLOT
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RESPONSE SURFACE PLOTF 4+1& //+!t1)t&! t"& !+1 ) & 1&!$%3!& $/%t %1 t"& 0%(&/ (&$ t&(.It !"%2! t")t " t%!)3 %3 &3t1)t %3 )3( %3 &3t1)t %3 % SGC ")! ) ! 43 )3t$%! t -& & & t %3 t"& 1&!$%3!& JSS @$ >.>< .
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11/20/15 56
. H&, W. G+%, X. Z")34, M., T1)3!(&10)/ $&10&)t %3 &3")3 &0&3t % N7t1 0&t"#/ " t%!)3 %1 t&!t%!t&1%3&. I3t&13)t %3)/ J%+13)/% P")10) &+t ! ;>> , =< @ 7; , ;.
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11/20/15 57
SEM
AMOUNT OF DRUG PERMEATED VS TIME FOR
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AMOUNT OF DRUG PERMEATED VS TIME FORBATCHES P P .
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In vitro permeation study
Time in hour s
A
m o u
n t o f d r u g r e l e a s e m c g / c m 2
0 1 2 3 4 5 6 7 8 9 100
500
1000
1500
2000
2500
P1
P2
P3
P4
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VALIDATION OF THE MODEL
C%3 &3t1)t %3% " t%!)3
C%3 &3t1)t %3% SGC
P1&( t&(J!!
A t+)/J!!
70+ 3+ 161.38 137.20
#tudent t te&t '< ( va ue E 0.0514*
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EFFECT OF INCLUSION COMPLEXON PERMEATION ENHANCEMENT
A *)t " 2)! $1&$)1&( 2" " %3t) 3&( t"& !)0& %10+/)t %3 %P ; *+t +1%!&0 (& 2)! 3 %1$%1)t&( 3 t"& %10 % 3 /+! %3
%0$/&6 2 t" HP787 CD. T" ! *)t " 2)! %(&( )! P
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B)t " %(&J SS @!t&)(#!t)t& /+6
@ 49 0; 9"1
P&10&)* / t# %& &3t
@ 09"1
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In vitro permeation study
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11/20/15 62
C%0$)1 !%3 % )0%+3t % (1+4 $&10&)t&( -&1!+! t 0& %1 /0!%3t) 3 34 +1%!&0 (& @P; )3( +1%!&0 (& %0$/&6 @P< .
In vitro permeation study
Time in hours
A m o u
n t o f r u ! r e " e # s e m c ! $ c m 2
0 1 2 3 4 5 6 7 8 9 100
500
1000
1500
2000
2500P2
P5
SWELLING INDEX AND
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SWELLING INDEX ANDSURFACE $H
It 2)! )/!% %*!&1-&( t"& $1% /& %1 2)t&1 "#(1)t %3 !t%$! ) t&1 &1t) 3 t 0&t" ! ! *& )+!& % $%%1 !%/+* / t# % " t%!)3 3 2)t&1 t"+! / + ( +$t) & !t%$!) t&1 &1t) 3 / 0 t. S 0 /)1 1&!+/t! 2&1& %+3( *# R%!! &t )/ =>, = .
11/20/15 63
. R%!! , S. S)3(1 , G. F&11)1 , F. B%3 &1%3 , M. C. C)1)0&//), C., B+ )/ D&/ -&1# % A # /%- 1 1%0 F /0! B)!&( %3 C" t%!)3)3( P%/#) 1#/ A (. P")10 D&- T& "3%/ ;>>=, @; , 7;> .;. H)!!)3, N. A/ , M. A/ , J., D&-&/%$0&3t )3( E-)/+)t %3 % N%-&/ B+ %)("&! -& 2) &1! % 3 0%( $ 3& %1 t1&)t0&3t %"#$&1t&3! %3 D1+4 D&/ - ;> >, ? @; , < 7 ?.
MECHANICAL PROPERTIES OF FILMS
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MECHANICAL PROPERTIES OF FILMSCONTAINING DRUG AND INCLUSION
COMPLEX
11/20/15 64
B)t " %(& T&3! /& !t1&34t"
@4900 ;E/%34)t %3 )t *1&)
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P ; >. = .;
P < >.; .
St+(&3t t7t&!t $ >.>= $ >.
S 0 /)1 1&!+/t 2)! %+3( *# B%)t&34 &t )/
;. B%)t&34, J. S. St&-&3!, H. N. E. E /&!t%3, G. M. A+ 1&t, A. D. H+0$"1, M. J. M)tt"&2!,K. H., D&-&/%$0&3t )3( 0& ")3 )/ ")1) t&1 ')t %3 % !%/-&3t7 )!t $%/#0&1 /0! )! $%t&3t )/(1+4 (&/ -&1# !#!t&0! t% 0+ %!)/ !+1 ) &!. D1+4 D&- I3( P")10 ;>> , =< @ , 7 .
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FILM STRENGTH BATCH P<
FILM STRENGTH BATCH P;
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MUCOADHESIVE TIMEA/!% 0+ %)("&! -& t 0& %1 *%t" t"& *)t "&! 2)!
%+3( t% " 4"&1 &3%+4" +$t% "%+1! )3( )*%-&.T" ! )3 *& )tt1 *+t&( t% /)14& -%/+0& % "#(1)t 34
/+ ( $1&!&3t t% "#(1)t& t"& /0 )3( )/!%, t"& %1 &)$$/ &( *# t"+0* t% !t t"& /0 t% t"& 0+ %!)/!+1 ) & 2)! " 4"&1.A/!% "#(1)t %3 % /0 ! 4%%( (+& t% $1&!&3 & % PVPK=> 3 t"& 0)t1 6.
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MUCOADHESIVE STRENGTH
T"&!& 1&!+/t! 2&1& %3! !t&3t 2 t" t"& 3( 34! 7=.
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. M+1), P. C%1t , G. C 11 , M. M)&!t1&// , F. M&33 3 , N. B1)4)43 , M., D&-&/%$0&3t % M+ %)("&! -&F /0! %1 B+ )/ A(0 3 !t1)t %3 % F/+ &3)0 A (: E & t % C# /%(&6t1 3 C%0$/&6)t %3. J%+13)/ %$")10) &+t )/ ! &3 &! ;> >, @? , => 7=>; .;. H)!!)3, N. A/ , M. A/ , J., D&-&/%$0&3t )3( E-)/+)t %3 % N%-&/ B+ %)("&! -& 2) &1! % 3 0%( $ 3& %1t1&)t0&3t % "#$&1t&3! %3 D1+4 D&/ - ;> >, ? @; , < 7 ?.=. M%1)/&!, J. O. M C%3- //&, J. T., M)3+ ) t+1& )3( ")1) t&1 ')t %3 % 0+ %)("&! -& *+ )/ /0!.E+1%$&)3 J%+13)/ % P")10) &+t ! )3( B %$")10) &+t ! ;> , ?? @; , ?7 .
B)t " %(& F%1 & %)("&! -&3&!! A("&! -&3&!!
P; 7 < 40 ;.;< 49!&
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MUCOADHESION STRENGTH 7P;
MUCOADHESION STRENGTH P<
IN VITRO DRUG RELEASE STUDY
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IN VITRO DRUG RELEASE STUDYKINETICS OF DRUG RELEASE
STUDY
I3 - t1% (1+4 1&/&)!& $1% /&! %1 /0! %3t) 3 34 +1%!&0 (& )3(+1%!&0 (&7HP787CD %0$/&6.
Time in hours
%
r u !
r e " e # s e
0 2 4 6 8 100
20
40
60
80
100P2P5
%n &itro ru! re"e#se
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CD %0$/&6 P
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CORRELATION COEFFICIENTS FORDIFFERENT MODELS FOR BATCH P ; AND P <
11/20/15 71
ode R 2 va ue '=uro&e)ide* 2R 2 va ue 'inc u&ion
co)< ex* 5
Z&1% %1(&1 1&/&)!& 0%(&/ 0.8777 >. ?>
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ix&on Crowe )ode 0.$132 0.$605H 4+ " ! 0%(&/ >. 0.$450
For&)e9erG& e
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KINETICS OF DRUG RELEASE
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T"& " 4+ " ! 0%(&/ 1&$1&!&3t! t2% / 0 t )!&! 3 t"&t1)3!$%1t )3( (1+4 1&/&)!& $"&3%0&3%3.I3 t"& (1+4 1&/&)!& $"&3%0&3%3 % t"& /0, t"& (1+40%/& +/&! ")-& t% ( +!& ) 1%!! +3!t 11&( ) +&%+! /)#&1%3 t"& 0&0*1)3& !+1 ) & 3 t"& (%3%1 %0$)1t0&3t
%//%2&( *# ( +! %3 ) 1%!! !&0 $&10&)*/& 0&0*1)3& t%t"& 1& &$t%1 %0$)1t0&3t.T"& %*!&1-&( 1&/&)!& 3&t ! 3( )t&! t")t t"& (1+4) 1%!! t"& 0&0*1)3& !+1 ) & ! ) 1)t& / 0 t 34 !t&$7 3%-&1)// (1+4 1&/&)!& $1% &!! .T"& %0$/&6 %3t) 3 34 /0 %//%2! Z&1% %1(&1 3&t !.C%0$/&6 %10)t %3 ) / t)t&( t"& ( +! %3 % (1+4 ) 1%!!t"& 0&0*1)3& )3( "&3 & 3 1&)!&( t"& ( !!%/+t %3 %(1+4.
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SUMMARYT"& *+ )/ /0! 2&1& (&-&/%$&( +! 34 !%/-&3t )!t 34 0&t"%(.T"& %10+/)t %3 2)! (&3t &( %1 t"& *) 34 /)#&1 )3(0+ %)("&! -& /)#&1.T% 3%2 t"& & & t % $%/#0&1 )3( $&10&)t %3 &3")3 &1 %3 t"&$&10&)* / t# % (1+4 t"1%+4" *+ )/ 0+ %!) ) ; ; ) t%1 )/ (&! 43
2)! &0$/%#&( t% !t+(# t"& & & t % ; 3(&$&3(&3t -)1 )*/&! )t ;/&-&/!. I3(&$&3(&3t -)1 )*/&!: %3 &3t1)t %3 % $&10&)t %3&3")3 &1 @SGC )3( %3 &3t1)t %3 % " t%!)3 )3( (&$&3(&3t-)1 )*/&: !t&)(# !t)t& /+6 J SS. D&! 43 &6$&1t !% t2)1& t1 )/-&1! %3 .>. @222.!t)t&)!&. %0 2)! +!&( t% (&1 -& )$%/#3%0 )/ & +)t %3 %1 t"& (&! 43.It 2)! %+3( %+t t")t " t%!)3 %3 &3t1)t %3 )3( %3 &3t1)t %3 %SGC ")! ) ! 43 )3t $%! t -& & & t %3 t"& 1&!$%3!& JSS @$ >.>< .
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SUMMARY
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SUMMARYT" ! %*!&1-)t %3 (&$ t! t")t 3 1&)!& 3 %3 &3t1)t %3 % " t%!)3 )!2&// )! SGC 3 1&)!&! t"& J
SS.
N&6t t"& %$t 0 '&( *)t " %*t) 3&( 1%0 t"& )*%-& &6$&1 0&3t)/ (&! 432)! %0$)1&( 2 t" t"& !)0& %10+/)t %3 % /0 %3t) 3 34 +1%!&0 (&
3 t"& %10 % 3 /+! %3 %0$/&6 2 t" HP787CD.E & t % %0$/&6)t %3 %3 t"& $&10&)* / t# % +1%!&0 (& 2)! &-)/+)t&(
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