AJPRHC Research Article

FORMULATION AND EVALUATION OF TOPICAL DICLOFENAC SODIUM GEL USING DIFFERENT GELLING AGENT Y. S. TANWAR1 , AMIT KUMAR JAIN*2 For Author affiliations see end of the text This paper is available o li e at !!!."prhc.i

ABSTRACT: The prese t research has bee # $erta%e !ith the ai& to $evelop a topical 'el (or&#latio o( )iclo(e ac so$i#& #si ' $i((ere t 'elli ' a'e t carbopol, Na *M*, +,M* -K.M/ a $ so$i#& al'i ate i $i((ere t co ce tratio , !hich !o#l$ atte #ate the 'astroi testi al relater to0icities associate$ !ith oral a$&i istratio . The1 !ere eval#ate$ (or ph1sicoche&ical properties s#ch as ho&o'e eit1, 'ritti ess, viscosit1, p+, Sprea$abilit1, $r#' co te t, s%i irrita c1, in vitro $r#' release, stabilit1 st#$ies. The in vitro drug release rate o( 'el !as eval#ate$ #si ' 2ra 3 $i((#sio cell co tai i ' cellopha e &e&bra e !ith phosphate b#((er p+ 4.5 as the receptor &e$i#&. St#$ies sho!e$ that $r#' release !as $ecrease !ith i crease i 'elli ' a'e t co ce tratio beca#se pol1&er co ce tratio i creases, viscosit1 i creases. )r#' !as absorbe$ (ro& site o( applicatio as lo ' as it re&ai s i hi'her co ce tratio 'elli ' a'e t i sol#tio (or&. Keywords: )iclo(e ac So$i#&, carbopol, h1$ro01l prop1l &eth1l cell#lose, so$i#& al'i ate a tii (la&&ator1 activit1. INTRODUCTION )iclo(e ac So$i#& is a pote t &e&ber o( the o steroi$al a ti6i (la&&ator1 $r#'s -NSAI)s/, !i$el1 #se$ beca#se o( its stro ' a al'esic, a tip1retic a $ a ti6i (la&&ator1 e((ects -162/. 7ral $ose o( $iclo(e ac potassi#& ca#ses a i crease$ ris% o( serio#s 'astroi testi al a$verse eve ts i cl#$i ' blee$i ', #lceratio a $ per(oratio o( the sto&ach or the i testi es !hich co#l$ be (atal. )#e to the prese ce o( these oral a$verse e((ects ecessitate the ee$ (or i vesti'ati ' other ro#te o( $r#' $eliver1 o( $iclo(e ac potassi#&. Tra s$er&al $eliver1 o( the $r#' ca i&prove its bioactivit1 !ith re$#ctio o( the si$e e((ects a $ e ha ce the therape#tic e((icac1 -86./. )eliver1 o( $r#'s to the s%i is a e((ective a $ tar'ete$ therap1 (or local $er&atolo'ical $isor$ers. This ro#te o( $r#' $eliver1 has 'ai e$ pop#larit1 beca#se it avoi$s (irst pass e((ects, 'astroi testi al irritatio , a $ &etabolic $e'ra$atio associate$ !ith oral a$&i istratio -964/. Topical 'el (or&#latio s provi$e a s#itable $eliver1 s1ste& (or $r#'s beca#se the1 are thi0otropic, 'reaseless, easil1 sprea$able, easil1 re&ovable, e&ollie t, o stai ', co&patible !ith several e0cipie ts a $ !ater6sol#ble or &iscible. ,erc#ta eo#s absorptio o( $r#'s (ro& topical (or&#latio s i volves the release o( the $r#' (ro& the (or&#latio a $ per&eatio thro#'h s%i to reach the tar'et tiss#e. The release o( the $r#' (ro& topical preparatio s $epe $s o the ph1sicoche&ical properties o( the vehicle a $ the $r#' e&plo1e$. -:6;/ S%i is o e o( the &ost rea$il1 accessible or'a s o( h#&a bo$1 (or topical a$&i istratio a $ &ai ro#te o( topical $r#' $eliver1 s1ste&. N#&bers o( &e$icate$ pro$#cts are applie$ to the s%i or &#co#s &e&bra e that either e ha ce or restore a (# $a&e tal (# ctio o( a s%i or phar&acolo'icall1 alter a actio i the # $erli e$ tiss#es. -1</ Topical $r#'s #se$ to co trol pai act locall1 o $a&a'e$ or $1s(# ctio al so(t tiss#es or peripheral erves, a $ their actio s &a1 be o the i (la&&ator1 respo se itsel( or o se sor1 e#ro s -11/. A i&prove$ )iclo(e ac (or&#latio !ith a hi'h $e'ree o( s%i per&eatio co#l$ be #se(#l i the treat&e t o( ot o l1 locall1 i (la&e$ s%i tiss#es, b#t also i (la&&ator1 a $ pai (#l states o( s#pporti ' str#ct#res o( the bo$1 bo es, li'a&e ts, "oi ts, te $o s a $ &#scles. -12/ The ob"ective o( prese t st#$1 !as co $#cte$ to $evelop a topical 'el (or&#latio o( $iclo(e ac so$i#& #si ' (o#r t1pes o( 'elli ' a'e ts= carbopol ;8., h1$ro01prop1l&eth1lcell#lose -+,M*/, carbo01&eth1lcell#lose so$i#& -Na *M*/ a $ so$i#& al'i ate (or e ha ci ' the s%i pe etratio . >((ect o( pe etratio e ha cer -prop1le e 'l1col/ o the release has bee st#$ie$. The 'els !ere eval#ate$ (or ph1sical appeara ce, rheolo'ical behavio#r, $r#' release a $ stabilit1. The $r#' release (ro& all 'elli ' a'e ts thro#'h a sta $ar$ cellopha e &e&bra e !as eval#ate$ #si ' 2ra 3 $i((#sio cell. MATERIALS )iclo(e ac So$i#& -?i(t sa&ple, )) ,har&a Jaip#r/ carbopol6;8., Na *M* salt &e$i#& viscosit1 2<<6.<< c,s, +,M* -K.M/, so$i#& al'i ate, prop1le e 'l1col, trietha ola&i e, prop1lparabe , so$i#& h1$ro0i$e, potassi#& $i h1$ro'e ortho phosphate, etha ol #se$ !ere a al1tical 'ra$e. METHODS Prepara !o" o# $e%s: *arbopol ;8. 'els !ere (or&#late$ b1 @rst prepari ' a stoc% sol#tio o( the *arbopol i $istille$ !ater a $ prop1le e 'l1col. Separatel1 )iclo(e ac so$i#& -1A!B!/ !as $issolve$ i pre!ei'hte$ a&o# ts o( prop1le e 'l1col a $ etha ol. Solve t ble $ !as tra s(erre$ to carbopol co tai er a $ a'itate$ (or a$$itio al 2< &i . The $ispersio !as the allo!e$ to h1$rate a $ s!ell (or 4< &i , (i all1 a$"#ste$ e#tral p+ b1 so$i#& h1$ro0i$e sol#tio !ith stirri '. All the sa&ples !ere

AJPRHC

Volume 4

Issue 1

1-6

allo!e$ to eC#ilibrate (or at least 2. ho#rs at roo& te&perat#re prior to per(or&i ' rheolo'ical &eas#re&e ts -1861./.-Table 1/ 7ther 'el (or&#latio s !ere prepare$ b1 $ispersi ' +,M*, Na *M* a $ so$i#& al'i ate i !ater b1 co ti #o#s stirri '. )iclo(e ac so$i#& !as $issolve$ i prop1le e 'l1col or etha ol a $ the sol#tio !as a$$e$ 'e tl1 to +,M*, Na *M* a $ so$i#& al'i ate $ispersio # $er co ti #o#s stirri '. The &i0t#re !as stirre$ 'e tl1 !ith a spat#la # til ho&o'e eo#s 'el !as (or&e$. All the sa&ples !ere allo!e$ to eC#ilibrate (or at least 2. h at roo& te&perat#re prior to per(or&i ' rheolo'ical &eas#re&e ts. C&ara' er!(a !o" o# For)*%a !o"s The prepare$ $iclo(e ac so$i#& 'els !ere i specte$ vis#all1 (or their ho&o'e eit1, 'ritti ess, viscosit1, Sprea$abilit1, p+, $r#' co te t, s%i irrita c1, in vitro $r#' release, stabilit1 st#$ies. Ho)o$e"e! y All $evelope$ 'els !ere teste$ (or ho&o'e eit1 b1 vis#al i spectio a(ter the 'els have bee set i the co tai er. The1 !ere teste$ (or their appeara ce a $ prese ce o( a 1 a''re'ates. -19/

Gr! !"ess All the (or&#latio s !ere eval#ate$ &icroscopicall1 (or the prese ce o( particles i( a 1 o appreciable partic#late &atter !as see # $er li'ht &icroscope. +e ce obvio#sl1 the 'el preparatio (#l(ils the reC#ire&e t o( (ree$o& (ro& partic#lar &atter a $ (ro& 'ritti ess as $esire$ (or a 1 topical preparatio . -19/ V!s'os! y The &eas#re&e t o( viscosit1 o( the prepare$ 'el !as $o e !ith a Droo%(iel$ visco&eter. The 'els !ere rotate$ at 2< a $ 8< rp& #si ' spi $le o. 4.. At each spee$, the correspo $i ' $ial rea$i ' !as ote$. -19/ Spreada+!%! y Sprea$abilit1 is e0presse$ i ter&s o( ti&e i seco $s ta%e b1 t!o sli$es to slip o(( (ro& 'el a $ place$ i bet!ee the sli$es # $er the $irectio o( certai loa$, lesser the ti&e ta%e (or separatio o( t!o sli$es, better the sprea$abilit1. -19/ It is calc#late$ b1 #si ' the (or&#la= S E M. F B T Where M E !ei'ht tie$ to #pper sli$e F E le 'th o( 'lass sli$es T E ti&e ta%e to separate the sli$es pH The p+ !as &eas#re$ i each 'el, #si ' a p+ &eter, !hich !as calibrate$ be(ore each #se !ith sta $ar$ b#((er sol#tio s at p+ ., :, ;. The electro$e !as i serte$ i to the sa&ple 1< &i priors to ta%i ' the rea$i ' at roo& te&perat#re. -14/ Dr*$ 'o" e" To e s#re # i(or& (or&#latio o( the 'el, it !as sa&ple$ (ro& the $i((ere t locatio s i the &i0er a $ assa1e$ (or the $r#' co te t. )r#' co te t o( the 'els !as $eter&i e$ b1 $issolvi ' a acc#ratel1 !ei'he$ C#a tit1 o( 'el -abo#t 1 '&/ i abo#t 1<< &l o( p+ 4.5 phosphate b#((er. -1:/ These sol#tio s !ere C#a titativel1 tra s(erre$ to vol#&etric (las%s a $ appropriate $il#tio s !ere &a$e !ith the sa&e b#((er sol#tio . The res#lti ' sol#tio s !ere the (iltere$ <..9 && &e&bra e (ilters be(ore s#b"ecti ' the sol#tio to spectrophoto&etric a al1sis (or $iclo(e ac so$i#& at 2:4 &. )r#' co te t !as $eter&i e$ (ro& the sta $ar$ c#rve o( $iclo(e ac so$i#&. S,!" !rr! a !o" The albi o &ice o( either se0 !ei'hi ' 2<22'&s !ere #se$ (or this test. The i tact s%i !as #se$. The hair !as re&ove$ (ro& the &ice 8 $a1s be(ore the e0peri&e t. The a i&als !ere $ivi$e$ i to t!o batches a $ each batch !as a'ai $ivi$e$ i to t!o 'ro#ps. The 'el co tai i ' $r#' !as #se$ o test a i&al. A piece o( cotto !ool soa%e$ i sat#rate$ $r#' sol#tio !as place$ o the bac% o( albi o &ice ta%e as co trol. The a i&als !ere treate$ $ail1 #p to seve $a1s a $ (i all1 the treate$ s%i !as e0a&i e$ vis#all1 (or er1the&a a $ e$e&a. In Vitro Re%ease The in vitro release e0peri&e ts !ere carrie$ o#t b1 #si ' 2ra 36$i((#sio cells apparat#s (ro& $i((ere t (or&#latio s. A e0act a&o# t o( (or&#latio s -1.< '/ !as sprea$ o#t o &e&bra e positio e$ bet!ee the $o or a $ receptor cha&bers !ith a available $i((#sio area. The receptor co&part&e t !as (ille$ !ith phosphate b#((er p+ 4.5 a $ co ti #o#sl1 stirre$ !ith a s&all &a' etic bar at a spee$ o( 9< rp& $#ri ' the e0peri&e ts to e s#re ho&o'e eit1 a $ &ai tai e$ at 8:.2G<.9 < *. The sa&ples !ere !ith$ra! at vario#s ti&e i tervals a $ replace$ !ith the sa&e vol#&e o( ,DS. Si % co $itio s !ere &et i all cases. The sa&ples !ere a al13e$ spectrophoto&etricall1 at 2:4 & -Shi&a$3# UH6Hisible615<</. S a+!%! y s *dy 2or the eval#atio o( stabilit1 st#$1, &ai tai i ' the (or&#latio s at a a&bie t co $itio over a perio$ o( t!o &o ths. The ph1sical appeara ce, p+ val#e, $r#' co te t, rheolo'ical properties, $r#' release st#$ies !ere $eter&i e$ perio$icall1 a(ter the 1st a $ 2 $ &o th a(ter topical 'el preparatio s. RESULTS AND DISCUSSION C&ara' er!(a !o" o# For)*%a !o"s The prepare$ (or&#latio s share$ a s&ooth a $ ho&o'e eo#s appeara ce. The *arbopol $iclo(e ac so$i#& 'els !ere tra spare t !hile +,M* a $ Na *M* 'els !ere !hite visco#s a $ so$i#& al'i ate 'els !ere bro! ish '#&&1 !ith s&ooth a $ ho&o'e eo#s appeara ce. All preparatio s !ere easil1 sprea$able, !ith acceptable bioa$hesio a $ (air &echa ical properties. The p+ val#es ra 'e$ (ro& 9.:1G<.15 to 4.52G<.2:, !hich are co si$ere$ acceptable to avoi$ the ris% o( irritatio a(ter s%i applicatio -15/. Hiscosit1 is a i&porta t ph1sical propert1 o( topical (or&#latio s, !hich a((ects the rate o( $r#' releaseI i 'e eral, a i crease o( the viscosit1 vehicles !o#l$ ca#se a &ore ri'i$ str#ct#re !ith a co seC#e t $ecrease o( the rate o( $r#' release -1;/.

AJPRHC

Volume 4

Issue 1

1-6

Hiscosit1 i crease$ -(ro& 2;8<..2G<.52 c,s to .2<5.89G1.81 c,s, Table 2/ as pol1&er co ce tratio i crease$. I crease$ co siste c1 !as ascribe$ to e ha ce$ pol1&eric e ta 'le&e ts, thereb1 i creasi ' the resista ce to $e(or&atio . -2</ 2or all (or&#latio s the viscosit1 !as (o# $ to be lo!er (ro& 2.8 to ..1 ti&es as the rotatio al spee$ i crease$. I (act, !he the spee$ i creases, the or&all1 $isarra 'e$ &olec#les o( the vehicle are ca#se$ to ali' their lo ' a0es i the $irectio o( (lo!. S#ch orie tatio re$#ces the i ter al resista ce o( the &aterial a $ he ce $ecreases the viscosit1. The res#lts o( s%i irrita c1 st#$ies are sho! that the prepare$ 'els $o ot pro$#ce a 1 s%i irritatio a $ are !ell tolerate$ b1 &ice. The res#lt o( stabilit1 st#$ies are sho! that there !ere o si' i(ica t cha 'es i the viscosit1, $r#' co te t a $ ph1sical appeara ce o( the 'el, a(ter stori ' at $i((ere t te&perat#re co $itio s (or three &o ths. These res#lts i $icate that $r#' re&ai stable a(ter stabilit1 st#$ies. In Vitro Re%ease Res*% s I vitro $issol#tio pro(ile o( $iclo(e ac so$i#& 'els co tai i ' $i((ere t co ce tratio o( carbopol, +,M*, Na *M* a $ so$i#& al'i ate are sho! i table 8 a $ (i'. 16.. Release pro(iles o( $iclo(e ac so$i#& (ro& vario#s 'el (or&#latio s across the cell#lose &e&bra e $eplicate$ that $r#' release $ecrease !ith i crease i co ce tratio o( the 'elli ' a'e t. The $r#' release val#es !ere also (o# $ lo!er (or the (or&#latio i !hich pol1&er co ce tratio !as %ept hi'h -Table 8/. I a$$itio , viscosit1 i crease$ -(ro& 2;4:G<.28 c,s to .45:G<.81 c,s, Table2/ as pol1&er co ce tratio i crease$. Hiscosit1 is e'ativel1 relate$ to the release o( active s#bsta ce (ro& (or&#latio s a $ its pe etratio thro#'h the $i((#sio barriers. The $ecrease i the release co#l$ be attrib#te$ to i crease$ &icroviscosit1 o( the 'el b1 i creasi ' pol1&er co ce tratio . Th#s, both hi'h co ce tratio o( pol1&er a $ hi'h viscosit1 co&pete each other i $ecreasi ' the release o( active s#bsta ce (ro& the (or&#latio . I o#r st#$1, the (i $i ' that hi'her pol1&er co ce tratio res#lte$ i lo!er $r#' release (ro& the vehicles is i a'ree&e t !ith Fa#((erJs &olec#lar $i((#sio theor1 o( pol1&er 'els, !hich states that the $i((#sio coe((icie t o( a sol#te is i versel1 proportio al to the vol#&e (ractio occ#pie$ b1 the 'el6(or&i ' a'e t. -21628/ Ta+%e -: D!##ere" $e% #or)*%a !o"s

S.N 1 2 8 . 9 4

I 're$ie ts -A!B!/ )iclo(e ac so$i#& *arbopol6;8. Na *M* +,M* So$i#& al'i ate ,rop1le e 'l1col Trietha ola&i e >tha ol ,rop1l parabe Water #p to

21 1 1 6 6 6 19

22 1 1.9 6 6 6 19

28 1 2 6 6 6 19

2. 1 6 1 6 6 19

29 1 6 1.9 6 6 19

2or&#latio 24 2: 1 1 6 2 6 6 19 6 6 1 6 19

25 1 6 6 1.9 6 19

2; 1 6 6 2 6 19

21< 1 6 6 6 1 19

211 1 6 6 6 1.9 19

212 1 6 6 6 2 19

: 5 ; 1<

<.. 8< <.9 1<<

<.9 8< <.9 1<<

<.4 8< <.9 1<<

<.. 8< <.9 1<<

<.9 8< <.9 1<<

<.4 8< <.9 1<<

<.. 8< <.9 1<<

<.9 8< <.9 1<<

<.4 8< <.9 1<<

<.. 8< <.9 1<<

<.9 8< <.9 1<<

<.4 8< <.9 1<<

Ta+%e .: P&ys!'o'&e)!'a% '&ara' er!s !'s o# d!'%o#e"a' sod!*) $e%s #or)*%a !o"s

For)*%a !o" FF. F1 F2 F3 F4 F5 F6 F7 F-8 F-F-.

Ho)o$e"e! y // /// /// // /// /// /// /// /// // /// //

Gr! !"ess 0 0 0 0 0 0 0 0 0 0 0 0

Spreada+!%! y 81.5:G1.9< 21.8.G1.21 1:.41G1.11 88.21G1.28 1;.<5G1.1: 12.41G1.<; 2:.:5G1.15 1..81G1..2 11.18G1.15 2..41G1.25 1:.11G1.<5 11.41G1.2:

pH 4.94G<.1; 4.52G<.25 4.:8G<.21 4.44G<.1: 4.:1G<.1; 9.:1G<.15 4.:9G<.21 4.44G<.1: 4.94G<.1: 4..9G<.14 4.44G<.14 4..8G<.19

V!s'os! y 82.9.81G1.11 8:5;.25G1.<1 .2<5.89G1.81 2;<5..2G<.52 8.:4.82G1.1< 8;49.5:G1.21 8121.88G1.:8 8499.4:G1..: .14:.29G1.81 821:..8G1.25 845:.88G1..2 .149..1G1.82

Dr*$ 'o" e" ;5.9.G<.18 ;:.:5G<.12 ;;.9:G<.1. ;:.8.G<.15 ;5.41G<.22 ;5.:2G<.<; ;4.5.G<.1: ;5.8;G<.1. ;;.9.G<.14 1<1.21G<.11 ;5.81G<.1: ;;.29G<.1;

AJPRHC

Volume 4

Issue 1

1-6

NE8 >0celle t KKK, ?oo$ KK, Satis(actor1 K, No 'ritti ess Ta+%e 1: C*)*%a !9e : Dr*$ re%ease #ro) $e% #or)*%a !o"s a d!##ere" !)e !" er9a%s For)*%a !o" C*)*%a !9e Re%eased !" )!" 1<..9 G <.<; 5.4: G <.<5 4.5: G <.<; 1..<9 G 1.<1 11.19 G <.4; ;.49 G <.:1 18.11 G <.:4 11.<9 G 1.<8 5.;5 G <.;< 1<.19 G <.4: 5.99 G <.5; 4.<9 G <.:2 : 48 C*)*%a !9e : Re%eased !" -.8 )!" 88.15 G <.28 25..9 G <..5 21.<9 G <.82 89.5: G 1.1; 8<.4. G <.;; 24.:: G <.5; 8..89 G <.8< 2;.;< G 1.<; 24.14 G <.:5 88.<1 G o.12 25..9 G <.42 21.:4 G <.9: C*)*%a !9e Re%eased !" )!" 51.21 G 1.12 :5.1; G <.5; :2.89 G <.45 5:.;< G 1.11 51..9 G 1.<; ::.82 G <.55 55.99G <.58 52.18 G 1.8. ::.11 G 1.11 5<.28 G 1.8: :5.<; G1..1 :1.4: G 1.29 : 148

FF. F1 F2 F3 F4 F5 F6 F7 F-8 F-F-. NE

' * ) * % a

r e % e a ! s 9 e e

90 80 70 60 50 40 30 20 10 0 306090120 1 50 1 80 2 10 2 40 2 70 3 00 3 30 3 60 T!)e ;M!"<

F1 F2 F3

2i'#re 1= *#&#lative A)r#' release (ro& carbopol ;8. 'el (or&#latio s at $i((ere t ti&e i tervals

2i'#re 2= *#&#lative A)r#' release (ro& Na *M* 'el (or&#latio s at $i((ere t ti&e i tervals

AJPRHC

Volume 4

Issue 1

1-6

2i'#re 8= *#&#lative A)r#' release (ro& +,M* 'el (or&#latio s at $i((ere t ti&e i tervals

2i'#re .= *#&#lative A)r#' release (ro& So$i#& Al'i ate 'el (or&#latio s at $i((ere t ti&e i tervals

CONCLUSION )iclo(e ac so$i#& is a o 6steroi$al a tii (la&&ator1 $r#' -NSAI)/ that e0hibits a tii (la&&ator1, a al'esic, a $ a tip1retic activities. To overco&e the si$e e((ects associate$ !ith oral $iclo(e ac so$i#& therap1 a $ to have the be e(its associate$ !ith topical therap1I $iclo(e ac so$i#& topical 'els are prepare$ i this st#$1. St#$ies sho!e$ that $r#' release !as $ecrease !ith i crease i 'elli ' a'e t co ce tratio beca#se pol1&er co ce tratio i creases, viscosit1 i creases. )r#' !as absorbe$ (ro& site o( applicatio as lo ' as it re&ai s i hi'her co ce tratio 'elli ' a'e t i sol#tio (or&. So !ith a i te tio to %eep the $iclo(e ac so$i#& i sol#tio (or&, a $ th#s prolo 'i ' the ti&e o( absorptio , 'el (or&#latio s !ere prepare$. A',"ow%ed$e)e" s The a#thors are tha %(#l to Mahat&a ?a $hi *olle'e o( ,har&ace#tical Scie ces (or provi$i ' (acilities. REFERENCES 1. 2. 8. .. Sa a H, ,ea a TA, Moretti )FM. >((ect o( vehicle o $iclo(e ac so$i#& per&eatio (ro& e! topical (or&#latio s= I vitro a $ I vivo st#$ies.*#rre t )r#' )eliver1. 2<<;, 4= ;861<<. S%o#ta%is HA, *arter *A, Mic%le TR, et al. Revie! o( $iclo(e ac a $ eval#atio o( its place i therap1 as a o steroi$al a ti6i (la&&ator1 a'e t. )r#' I tell. *li . ,har&. 1;55,22= 59<69;. K#&ar H, Sathali A+, K#&ar A. 2or&#latio a $ eval#atio o( $iclo(a ac potassi#& ethoso&es. I t. J. o( ,har&ac1 a $ ,har&. Sci. 2<1<, 2= 52654. 2it3?eral$ ?, ,atro o *. The co0ibs selective i hibitors o( c1cloo01'e ase62. N > 'l J Me$. 2<<1, 8.9= .88L.2.

AJPRHC

Volume 4

Issue 1

1-6

9. 4.

:. 5. ;. 1<. 11. 12. 18. 1.. 19. 14. 1:. 15. 1;. 2<. 21. 22. 28.

Ki%!ai F, Dab# RJ, ,ra$o RA, et al. I vitro a $ I vivo eval#atio o( topical (or&#latio s o( spa ti$e II. AA,S ,har&. Sci Tech. 2<<9, 4= >9426:2. Dehl *, *har +S, ,atel SD, et al. I vivo a $ i vitro s%i #pta%e a $ per&eatio st#$iesI critical co si$eratio s a $ (actors, !hich a((ect the&. I = Shah D,, Maibach +I, e$s. Topical )r#' Dioavailabilit1, DioeC#ivale ce a $ ,e etratio . Ne! Yor%, NY= ,le #& ,ressI 1;;8, 229629;. ?ree ,?, 2la a'a M, Shroot D, ?#1 R+. Io otophoretic $r#' $eliver1. I = Walters K.A., +a $'ra(t J. e$s. ,har&ace#tical s%i pe etratio e ha ce&e t. Ne! Yor%, NY= Marcel )e%%er. 1;;8, 8116888. ,atel J, ,atel D, Da !ait +, et al. 2or&#latio a $ eval#atio o( topical aceclo(e ac 'el #si ' $i((ere t 'elli ' a'e t. I t. J. o( )r#' )ev. M Res. 2<11, 8= 194614.. )e1 S, Ma3#&$ar D, ,atel JR. > ha ce perc#ta eo#s per&eabilit1 o( ac1clovir b1 )MS7 (ro& topical 'el (or&#latio . I t. J. o( ,har&a. Sci. a $ $r#' Res. 2<<;, 1= 18615. ?#pta A, Mishra AK, Si 'h AK, et al. 2or&#latio a $ eval#atio o( topical 'el o( $iclo(e ac so$i#& #si ' $i((ere t pol1&ers. )r#' I ve tio To$a1. 2<1<, 2= 29<6298. Sa!1 o% J. Topical a $ ,eripherall1 Acti ' A al'esics. J. ,har&acol. Rev.2<<8,99= 162<. Shah NH, Sheth NS, Mistr1 RD, et al. IN vitro release o( $iclo(e ac so$i#& (ro& $i((ere t topical vehicles. I t. J. o( ,har&. Sci. 2<11, 2= S68168; ,atel R,, ,atel ++, Daria A+. 2or&#latio a $ eval#atio o( carbopol 'el co tai i ' liposo&es o( %etoco a3ole. I t. J. o( )r#' )el. Tech. 2<<;, 1= .2 L .9. Arella o A, Sa to1o S, Marti *, Y'art#a ,. I (l#e ce o( prop1le e 'l1col a $ isoprop1l &1ristate o the i vitro perc#ta eo#s pe etratio o( $iclo(e ac so$i#& (ro& carbopol 'els. >#r J. ,har&. Sci. 1;;5, := 12;689. Ka#r F,, ?ar' R, ?#pta ?). )evelop&e t a $ eval#atio o( topical 'el o( &i o0i$il (ro& $i((ere t pol1&er bases i applicatio o( alopecia. I t. J. ,har&ac1 a $ ,har&. Sci. 2<1<, 2= .86.:. Shivhare U), Jai KD, Math#r HD, et al. 2or&#latio $evelop&e t a $ eval#atio o( $iclo(e ac so$i#& 'el #si ' !ater sol#ble pol1acr1la&i$e pol1&er. )i'est Jo#r al o( Na o&aterials a $ Diostr#ct#res. 2<<;, .= 259 L 2;<. Sera UH, Ra&a a MH. I vitros%i absorptio a $ $r#' release L a co&pariso o( (o#r co&&ercial h1$rophilic 'el preparatio s (or topical #se. The I $ia ,har&acist. 2<<4, :8= 894684<. US, The 7((icial *o&pe $ia o( sta $ar$ 2irst a #al Asia e$itio . 2<<2, 99.. F#cero MJ, Hi'o J, Feo MJ. A st#$1 o( shear a $ co&pressio $e(or&atio s o h1$rophilic 'els o( treti oi . I t. J. ,har&.1;;.,1<4= 129688. ,ose6Hilar ovo D, Ro$ri'#e36Te reiro *, )os Sa tos J2R, et al. Mo$#lati ' the $r#' release !ith c1clo$e0tri s i h1$ro01prop1l &eth1lcell#lose 'els a $ tablets. J. *o trol. Release. 2<<.,;.= 891648. )ha!a S, Me$hi D, *hopra S. 2or&#latio a $ eval#atio o( $iltia3e& h1$rochlori$e 'els (or the treat&e t o( a al (iss#res. Sci ,har&. 2<<;, ::= .49L.52. ,ra%ash ,R, Rao N?R, *ho!$ar1 S. 2or&#latio , eval#atio a $ a ti6i (la&&ator1 activit1 o( topical etorico0ib 'el. Asia J. o( ,har&. a $ *li ical Res. 2<1<, 8= 124. Fa#((er MA. Theor1 o( )i((#sio i ?els. 1;41, 1= 2<96218.

AUTHORS AFFILIATIONS AND ADDRESS FOR CORRESPONDENCE D. N. *olle'e o( ,har&ac1, U$aip#r Mahat&a ?a $hi *olle'e o( ,har&ace#tical scie ces, Jaip#r >&ail= "ai a%<4N'&ail.co& Mob= K;16;55::.92:4

AJPRHC

Volume 4

Issue 1

1-6