Vol. 10, No.

2, Desember 2009

ISSN 1411 4283

Jurnal Farmasi Indonesia

P !"#!$%N
P&arma'eu(i'al Journal o) Indonesia
*erbi( dua +ali se(a&un, se(ia, Juni dan Desember Susunan Pen-urus.
Penan--un- Ja/ab 0e(ua Pen1un(inSe+re(aris Pen1un(inPen1un(in- !&li . . . . Dra. Nurul #u(maina&, #.Si., !,(. Dr.#u&ammad Da2i, #.Si., !,(. "a(na 3uliani, #.4io(e'&.,s(. Pro). Dr. !'&mad #urs1idi, #.S'., !,(. Pro). Dr. !'&mad Fud&oli, D5!., !,(. Dr. #.0us/andi, S6., #.P&il.,!,(. Dr. Suba-us 7a&1uono, #.S'., !,(. Nur'a&1an(i 7., #.4iomed., !,(. 5rind1a& "e(no 7., #.Si., !,(. 7a&1u 6(ami, #.Si., !,(. !-un- Sis/an(o, S5. Su1a(no 2 +ali se(a&un Juni 2000

Pen1un(in- Pela+sana

Dis(ribusi 8 Pemasaran 0ese+re(aria(an Periode ,enerbi(an Volume ,er(ama

. . . .

P&arma'on, meru,a+an 9urnal ilmia& 1an- memua( nas+a& &asil ,eneli(ian, sur:e1 dan (elaa& ,us(a+a bidan- +e)armasian, +ese&a(an, biolo-i mole+uler dan lin-+un-an &idu,.

!lama( "eda+si. Fa+ul(as Farmasi 6ni:ersi(as #u&ammadi1a& Sura+ar(a Jl. !&mad 3ani, *romol Pos I Pabelan 0ar(osuro Su+o&ar9o *el,. ;02<1= <1<41< 5>(. 1?<, 1?8, 1<@ Fa>. ;02<1= <1@448 5Amail. ,&arma'1Bums.a'.id

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!ssalamu2alai+um 7r.7b. Se-ala ,u9i &an1a un(u+ !lla& S7*, Ca( 3an- #a&a #emberi, 1an- (ela& memberi+an +aruniaAN1a se&in--a P&arma'on Volume 10 Nomer 2 ini da,a( (er/u9ud +e &ada,an ,emba'a. "eda+si men-&adir+an masin-Amasin- 2 ;dua= ar(i+el (en(an- a+(i:i(as an(io+sidan dan sin(esis analo- +ur+umin. 0ur+umin masi& menari+ un(u+ men9adi ba&an +a9ian sin(esis oba(, demi+ian ,ula usa&a e+,lorasi sen1a/a an(io+sidan alami. Sa(u ar(i+el (en(an- )ormulasi sediaan oba( di&adir+an un(u+ mera-am+an edisi +ali ini. Dan (era+&ir adala& ar(i+el berla(ar )arma+olo-i 1an- meneli(i (en(an- a+(i:i(as an(i,ire(i+ ba&an alam. 0ami masi& selalu menan(i+an saran dan +ri(i+. Semo-a P&arma'on Volume 10 Nomer 2 ini da,a( berman)aa(. Selama( memba'a. 7assalamu2alai+um 7r. 7b

"eda+si

Vol. 10, No. 2, Desember 2009

ISSN 1411 4283

Jurnal Farmasi Indonesia

P&arma'eu(i'al Journal o) Indonesia

P !"#!$%N
D!F*!" ISI

$a(a(an "eda+si Da)(ar Isi 69i !+(i:i(as Penan-+a, "adi+al DPP %le& !nalo- 0ur+umin #ono+e(on Dan NA e(eroali)a(i+ #ono+e(on #u&ammad DaDi, Nilu& 3uni !s(u(i dan 7a&1u 6(ami %,(imasi Sin(esis Sen1a/a !nalo- 0ur+umin Dime(ilbenEilidin=6rea Pada "en(an- , 3A4 !rdian !di Sa,u(ro, #u&ammad Da2i, 7a&1u 6(ami 1,3A4isA;4A idro+siA3,@A

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Iden(i)i+asi Dan !+(i:i(as !n(io+sidan Fra+si Non Polar 5+s(ra+ 5(anol Daun Sri+a1a ;!nnona SFuamosa .G= Den-an #e(ode DPP ar1o(o, !ndi Su&endi, !&/an Formulasi Pa('& 4u+al #u+oad&esi) Pro,ranolol $l Se(1oNur/aini, 5rin D.". 7i+an(1asnin-, Febrind$&andi+a N#. Po(ensi 5)e+ !n(i,ire(i+ Daun 0eman-i ;%'imum san'(um G.= Dan Daun De/a ;H1nura ,seudo'&ina ;G= D.$= 5# Su(risna, !ri)a& Sri 7a&1uni, Sri se(1o/a(i, Irna *ri/inarsi& Sin(esis Sen1a/a !nalo- 0ur+umin 3,?A4isA;42A idro+siA32,@2ADime(ilbenEilidin=A Pi,eraEinA22,@2ADion Den-an 0a(alis $l "e(no ari 7a&1uni, #u&ammad Da2I, 4ro(o San(oso

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F%"#6G!SI P!*$ 460!G #60%!D 5SIF P"%P"!N%G%G $l F%"#6G!*I%N %F #6$%!D 5SIV5 46$$!G P!*$ %F P"%P"!N%G%G $l Se(1o Nur/ainiI, 5rin D.". 7i+an(1asnin-, Febrind $&andi+a N#. Fa+ul(asFarmasi,6ni:ersi(as #u&ammadi1a&Sura+ar(a Se(1oJnur/ainiB1a&oo.'om !4S*"!0 Pro,ranolol $l men-alami me(abolisme lin(as ,er(ama &a(i ,ada ,ema+aian se'ara oral, den-an +e(ersediaan &a1a(i an(ara 1@A23K. Sala& sa(u u,a1a un(u+ menin-+a(+an +e(ersediaan &a1a(i ,ro,ranolol $l adala& den-an mem)ormulasi dalam ben(u+ sediaan ,a('& bu+al mu+oad&esi). Pa('& bu+al mu+oad&esi) ,ro,ranolol $l dibua( den-an me(ode dis,ersi,men--una+an berba-ai,erbandin-an +adar sodium $#$ seba-ai ma(ri+ dan ,oli:inil,irolidon ;PVP=seba-ai 'rossAlin+er. Pa('& diu9i si)a( )isi+n1a 1an- meli,u(i +esera-aman bobo( dan u+uran, +emam,uan men-emban-, , , dan /a+(u mu+oad&esi. 69i disolusi dila+u+an selama ? 9am, dan,ene(a,an+adardila+u+anden-anme(ode 6VAVis s,e'(ro)o(ome(ri. asil ,eneli(ian menun9u++an ,a('& memili+i +esera-aman bobo( dan u+uran. , ,a('& an(ara ?,?A< se&in--a (ida+ men-iri(asi ron--a mulu(. Penamba&an PVP men1ebab+an ,enin-+a(an +emam,uan men-emban- sodium $#$ &in--a 3 +ali li,a(. Penamba&an ,ro,ranolol $l dan PVP menurun+an /a+(u mu+oad&esi sodium $#$. Penamba&an PVP 1an- sema+in besar 'enderunmem,erlama ,ele,asan oba(, sedan-+an ,enamba&an PVP sebesar @0 m- menun9u++an ,ro)il ,ele,asan oba( ,alin- (in--i.

0a(a +un'i . ,a('& bu+al mu+oad&esi), Pro,ranolol $l, Sodium $#$, PVP !4S*"!$* Pro,ranolol $l under-oes )irs( ,ass me(abolism /&en used orall1, /i(& bioa:ailabili(1 o) be(/een 1@A23K. *&is resear'& /as aimed (o )ormula(e ,ro,ranolol $lin(o mu'oad&esi:ebu''al ,a('& dosa-e )orms in order (o im,ro:e i(s bioa:ailabili(1. Pro,ranolol $lmu'oad&esi:ebu''al ,a('&es /as usin- dis,ersion me(&od, /i(& di))eren( ra(io o) sodium $#$ as ma(ri> and ,ol1:in1l,1rrolidone ;PVP= as 'rossAlin+er. Pa('&es /ere e:alua(ed )or (&e ,&1si'al '&ara'(eris(i's su'& as uni)ormi(1 o) /ei-&( and siEe, s/ellin- abili(1, sur)a'e , , and mu'oad&esion (ime. Dissolu(ion (es( /as 'arried ou( )or ? &ours and (&e dru- 'on'en(ra(ion /as de(ermined usin- 6VA Vis s,e'(ro,&o(ome(r1. *&e resul(s s&o/ed (&a( all ,a('&es &ad-ood uni)ormi(1 o) /ei-&( and siEe. *&e sur)a'e , o) all ,a('&es /as be(/een ?,? and < and &en'e ,a('&es s&ould no( 'ause irri(a(ion in (&e bu''al 'a:i(1. *&e addi(ion o) PVP in ,a('& in'reased (&e s/ellin- inde> o) sodium $#$b1 (&ree (imes. Pro,ranolol $l and PVP in ,a('& redu'ed (&e mu'oad&esion (ime o) sodium $#$. In'reasin- PVP 'on'en(ra(ion lo/ered (&e dissolu(ion e))i'ien'1 :alue, /&ereas (&e addi(ion o) @0 m- o) PVP resul(ed in (&e &i-&es( dissolu(ion e))i'ien'1 :alue.

0e1/ords. mu'oad&esi:e bu''al ,a('&, Pro,ranolol $l, Sodium $#$, PVP P5ND! 6G6!N $ara ,en-&an(aran oba( melalui mu+osa mulu( da,a( dila+u+an melalui sublin-ual ;diba/a& lida&= a(au disisi,+an di an(ara -usi dan ,i,i ;bu+al=. Pema+aian se'ara bu+al lebi& disu+ai dari,ada sublin-ual +arena mu+osa bu+al+uran-,ermeabeldibandin-+an sublin-ual. *in--in1a ,ermeabili(as mu+osa sublin-ual men1ebab+an ru(e ini men-&asil+an onse( o) a'(ion 1an- 'e,a( se&in--a &an1a 'o'o+ un(u+ oba( 1an- membu(u&+an /a+(u ,en-&an(aran 1an- sin-+a( den-an ,emberian 1an- (ida+ (erlalu serin-. #u+osa bu+al +uran,ermeable, se&in--a (ida+ men-&asil+an onse( o) absor,(ion1an- (erlalu 'e,a(. 0ondisi ini 'o'o+ un(u+ sediaan sus(ained release ; arris dan "obinson, 1992=. Di sam,in- i(u, mu+osa bu+al memili+i o(o(Ao(o( 1an- lembu(, memili+i immobile mu+osa 1an- 'u+u, ban1a+, dan (ida+ serin- (er+ena air luda& se,er(i area sublin-ual ;S&o9aei, 1998= se&in--a meru,a+an area 1an- lebi& 'o'o+ un(u+ ,en-&an(aran oba( se'ara (ransmu+osa melalui mulu(. 4ebera,aben(u+sediaanun(u+ ,ema+aian bu+al adala& (able( ;Narendra e( al., 200@=, )ilm, ,a('& ;Nair dan $&ien, 199?=, dis+, s(ri, ; an-o e( al., 199<=, sale, dan -el ;S&in e( al., 2000=. Pa('& san-a( )le+sibel dan lebi& di(oleransi ole& ,asien dibandin-+an sediaan (able(. Pa('& 9u-a men9amin dosis 1an- (e,a(

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P !"#!$%N, Vol. 10, No. 2, Desember 2009, Nur/aini,S.,e( al. ;@<A?3=

dibandin-+an -el dan sale, ;Pa(el e( al., 200<=. Dalam ,en-emban-an sediaan ,a('& bu+al, mu+oad&esi meru,a+an &al 1an,en(in-. Polimer 1an- di-una+an seba-ai ba&an ma(ri+ mu+oad&esi) (eru(ama meru,a+an ,olimer &idro)ili+ anioni+ den-an se9umla& -u-us ,emben(u+ i+a(an &idro-en, memili+i ,ermu+aan 1an- 'o'o+ un(u+ ,embasa&an ole& mu+us, dan 'u+u, )le+sibel un(u+ memasu+i 9arin-an mu+us a(au 'ela& 9arin-an ;7ani, 200<=. Sodium +arbo+sime(il selulosa ;sodium $#$= meru,a+an ,olimer &idro)ili+ anioni+ dan (erbu+(i 'o'o+ di-una+an seba-ai ma(ri+ un(u+ sediaan ,a('& an(i9amur dan memili+i +e+ua(an mu+oad&esi 1an- ,alin- +ua( dibandin-+an $arbo,ol 934P, ,olie(ilen o+sida, ,olime(il:inile(erLmalea( an&idrida, dan (ra-a+an ;Nair dan $&ien, 199?=. Penamba&an Poli:inil,irolidon ;PVP= da,a( menin-+a(+an ,ele,asan oba( den-an 'ara menin-+a(+an ,en-emban-an ,olimer ;sodium $#$= ser(a menin-+a(+an elas(isi(as dan ,emben(u+an )ilm ,ada ,a('& ;Na)ee e( al., 2003M Pa(el e( al., 200<=. %ba( 1an- 1an- men-alami me(abolisme lin(as ,er(ama di &a(i 'o'o+ diberi+an dalam ben(u+ sediaan bu+al. S1ara( 1an- &arus dimili+i oba( (ersebu( dian(aran1a bobo( a(om +e'il ;+uran- dari @00 Da=, /a+(u ,aru& eliminasi (ida+ (erlalu renda&, ,o(en ;dosis ,emberian +e'il= ;S&ar-el e( al., 200@=, dan (i(i+
N

GSA?D*=, mi+ro,i,e( berba-ai u+uran, (i, ,i,e( ;biru, ,u(i&, +unin-=, dissolu(ion (es(er ;Van-uard= dan ala(Aala( -elas 1an- laEim di-una+an di labora(orium analisis. Jalann1a ,eneli(ian Pembua(an ,a('& bu+al mu+oad&esi) ,ro,ranolol $l Pa('& dibua( men-andun- Pro,ranolol $l 10 m- dan ma(ri+ sodium $#$ 1an- dibua( den-an me(ode dis,ersi ;Nori+o e( al., 199?=. Se9umla& 1 - sodium $#$ didis,ersi+an dalam 100 mG a+uades ,anas sambil diadu+. Garu(an +oloid 1an- di&asil+an dibiar+an din-in +emudian di(amba& den-an PVP dan ,ro,ranolol $l den-an ,en-adu+an +ons(an. Pro,ilen -li+ol ;@K:L:= di(amba&+an +e dalam 'am,uran den-an ,en-adu+an. Garu(an +en(al ini +emudian didiam+an selama semalam ,ada su&u ruan- a-ar men-&asil+an laru(an 1an9erni& bebas dari -elembun-. Garu(an di(uan-+an +e dalam 'e(a+an dan dibiar+an men-erin- ,ada su&u ruan- dan (erben(u+ )ilm 1an- )le+sibel. Film 1an- (ela& di+erin-+an di,o(on-A,o(on- den-an diame(er 1? mm un(u+ se(ia, ,a('&, men-andun- 10 m,ro,ranolol $l. Pa('& dibun-+us den-an aluminium )oil dan disim,an dalam /ada& (er(u(u,ra,a(un(u+mem,er(a&an+an elas(isi(as ,a'(&. 0om,osisi dari se(ia, )ormula ,a('& (ersa9i dalam *abel 1.

lebur +uran- dari 200 $ ;4ra'&(, 200<=. Pro,ranolol $l meru,a+an a-en ,emblo+ be(a adrener-i+ nonsele+(i) 1an- di-una+an se'ara luas un(u+ ,enan-anan &i,er(ensi, an-ina ,e+(oris, dan -an--uan +ardio:as+uler lainn1a ;!nonim, 200<=.Pro,ranolol $l men-alami me(abolisme lin(as ,er(ama &a(i 1an- san-a( ber:ariasi ,ada ,ema+aian se'ara oral, den-an +e(ersediaan &a1a(i an(ara 1@A23K ;!nonim, 200<=. Si)a( )isi+o+imia Pro,ranolol $l, /a+(u ,aru& eliminasi 3A? 9am, bobo( mole+ul 1anrenda& ;29@,81 Da= ;!nonim, 19<9= membua( Pro,ranolol $l san-a( (e,a( un(u+ dibua( sediaan den-an ru(e bu+al. 4erdasar uraian di a(as ma+a dila+u+an )ormulasi ,a('& ,ro,ranolol $l 1an- dibua( den-an men--una+an ma(ri+ mu+oad&esi) sodium $#$ dan ,enamba&an PVP.

*abel1A"an'an-an Formula Pa('& 4u+al#u+oad&esi) Pro,ranolol $l 4a('&0om,onen PlaseboF1F2F3F4F@ Pro,ranolol32323232 $l ;m-=03200000 Sodium1009@908@80 $#$ ;m-=100000000 101@20 PVP ;m-=00@0000 Pro,ilen-li+ ol ;K=0@@@@@

#5*%D5 P5N5GI*I!N 4a&an Pro,ranolol $l ;)armase(is=, Sodium $#$ ;4ra(a'&em=, PVP ;#er'+=, Na$l ;#er'+=, Pro,ilen -li+ol, me(&anol ;#er'+=. !Fuades( ;4ra(a'&em=. !la( S,e+(ro)o(ome(er Henes1sA10, +u:e( Fuar(E ; ilma=, nera'a ele+(ri+ ;S&imadEu, (1,e

Pene(a,an ,an9an- -elomban- ma+simal ,ro,ranolol $l Pro,ranolol $l 0,002K dalam me(anol ,ada ,en-u9ian ,ada ,an9an- -elombanan(ara 230A3@0 nm menun9u++an sera,an ma+simum ,ada 290 nm sebesar 0,84 ;!nonim, 19<9=. Pada ,er'obaan ini dila+u+an ,ene(a,an ,an9an- -elomban- ma+simal ,ro,ranolol $l den-an men--una+an ,elaru( laru(an bu)er )os)a( iso(onis , ?,8. Pro,ranolol $l 0,001K dalam laru(an bu)er )os)a( iso(onis , ?,8 diba'a ,ada ,an9an- -elomban- 2<@A 310 nm den-an men--una+an blan-+o laru(an bu)er )os)a( iso(onis , ?,8.

Pene(a,an +ur:a ba+u ,ro,ranolol $l Se9umla& laru(an s(o+ ,ro,ranolol $l dalam laru(an bu)er )os)a( iso(onis , ?,8

P !"#!$%N, Vol. 10, No. 2, Desember 2009,Nur/aini,S., e( al. ;@<A?3=

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diba'a sera,ann1a ,ada ,an9an- -elombanma+simal. Pen-u9ian dila+u+an seban1a+ 3 +ali. 0ur:a ba+u dibua( den-an mem,lo(+an +adar ,ro,ranolol $l seba-ai O dan sera,an 1andi&asil+an seba-ai 3 dalam ,ersamaan re-resi linier. 69i Fisi+ a. 69i 0esera-aman 4obo( dan 6+uran 0esera-aman bobo( diu9i den-an 'ara diambil @ sam,el se'ara a'a+ dari se(ia, ba('& dan di(imban- den-an nera'a anali(i+. Sedan-+an un(u+ ,en-u9ian u+uran ,a('&, dila+u+an den-an 'ara diambil @ sam,el se'ara a'a+ dari se(ia, ba('&. 69i +esera-aman u+uran dila+u+an den-an men-u+ur ,an9an- dan lebar masin-Amasin- sam,el ser(a +e(ebalann1a den-an 9an-+a soron- ;Pa(el e( al., 200<=.

d. 69i , Permu+aan Pa('& Pa('&1an-(ela&men-emban-, dimasu++an ,ada 1 ml air dis(ilasi ;, ?,@ 0,1= selama 2 9am ,ada su&u ruan-an. Pen-u+uran, dila+u+anden-an menem,el+an uni:ersal , ,ada ,ermu+aan ,a('& selama 1 meni(, +emudian , di'a(a( ;Pa(el e( al., 200<=. 69i ,ele,asan ,ro,ranolol $l se'ara in :i(ro 69i ,ele,asan ,ro,ranolol $l dari ,a('& men--una+anme(ode-a1un-;,addle= ber,u(arden-an medium dissolusi @00 mG bu)er )os)a( iso(onis , ?,8 1an- bersu&u 3<P $. Ha1un- di,u(ar den-an +e'e,a(an @0 r,m. Sala& sa(u sisi ,a('& dile+a(+an den-an ,e(ri dis+ den-an lem ins(an ;'1anoa'r1la(e=. Pe(ri dis+ dile(a++an di ba-ian ba/a& (abundissolusi se&in--a ,a('& (e(a, berada di a(as ,e(ri dis+. Se9umla& @,0 mG sam,el dan diba'a ,ada ,an9an- -elomban- ma+simal. Se9umla& :olume 1an- sama dari bu)er )os)a( iso(onis , ?,8 dimasu++an +e dalam (abun- dissolusi seba-ai ,en--an(i sam,el 1an- diambil. Pemba'aan dila+u+an den-an in(er:al /a+(u30 meni( ;Pa(el e( al., 200<=.

b. 69i 0emam,uan #en-embanPa('& bu+al 1an- (ela& di(imban-, dile(a++an ,ada 2K a-ar -el ,la(e dan
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diin+ubasi ,ada su&u 3< 1 $. Se(ela& diin+ubasi an(ara 1 9am sam,ai den-an 3 9am, ,a('& di,inda&+an +e 'a/an ,e(ri dan air 1anmenem,el ,ada ,ermu+aan den-an +er(as sarin-di&ilan-+an.Pa('&1an-(ela& men-emban-+emudiandila+u+an ,enimban-an la-i dan di&i(un- inde+s ,en-emban-ann1a.Per'obaan(ersebu( +emudian dire,li+asi (i-a +ali dan dila,or+an ra(ara(an1a ;Pa(el e( al., 200<=. '. 69i 7a+(u #u+oad&esi #u+osa bu+al +ambin- se-ar, diisi+an dalam bea+er -lass sam,ai den-an 2,@ 'm den-an di(amba&+an '1noa'r1la(e -lue. 0emudian ,a('& 1an- (ela& dibasa&i (erlebi& da&ulu den-an bu))er iso(oni+ )os)a( den-an , ?,8 di(em,el+an ,ada mu+osa bu+al +ambinse-ar 1an- (ela& disia,+an. 4e+er -elas +emudian diisi den-an @00 ml bu))er iso(oni+
o

)os)a( , ?,8 ,ada su&u 3<1 $. Se(ela& 2 meni(, diadu+ den-an +e'e,a(an @0 r,m un(u+ men--ambar+an suasana dibu+al. 0emudian dila+u+an ,en-ama(an (en(an- +ele+a(an ,a('&. 7a+(u 1an- dida,a(+an un(u+ mele,as+an ,a('& dari bu+al mu+osa +ambin-, di'a(a( seba-ai /a+(u mu+oad&esi ;Pa(el e( al., 200<=.
*abel2A asil69iSi)a(Fisi+ Pa('& 4u+al#u+oad&esi) Pro,ranolol $l 69i Fisi+PlaseboF1F2 0esera-aman bobo( ;m-=3@,@ Q 2,44@3,88 Q 1,0?@<,2 Q 0,<8 0e(ebalan ,a('& ;mm=1,1 Q 2,21,@ Q 01,@ Q 0 , ,ermu+aan?,4 Q 0,4?,8 Q 0,4@?,8 Q 0,4@ Inde+s Pen-emban-an ;K=9,8< Q 0,411@,?0 Q 2,48 41,0@ Q 9,3? 7a+(u mu+oad&esi ;meni(=148,33Q2<,@22,33Q2,@239,?<Q8,?2

!SIG D!N P5#4! !S!N 69i si)a( )isi+ ,a('& ,a('& bu+al mu+oad&esi) ,ro,ranolol $l 0esera-aman bobo( 1an- di&asil+an an(ara 3@,@ Q 2,44 m- sam,ai den-an <1,24 Q 3,9? m-. Perbedaan bobo( an(ara F1 sam,ai F@ disebab+an +arena adan1a ,en1usu(an +andun-an air +e(i+a disim,an dalam almari es seba-ai (em,a( ,en1im,anan. Pen1usu(an bobo( 1an- (er9adi ,ada &asil ,eneli(ian ini mem,en-aru&i +andun-an air ,ada ,a('&, (e(a,i Ea( a+(i) (ida+ i+u( (er,en-aru&. Gama ,en1im,anan men9adi )a+(or 1an- menen(u+an (er9adin1a:ariasi+esera-amanbobo(. Perbedaan bobo( an(ara ,lasebo den-an )ormula lainn1a dia+iba(+an +arena adan1a ,erbedaan +andun-an ,ada )ormulasin1a. Pada ,lasebo (ida+ menda,a(+an ,enamba&an ,ro,ilen-li+ol seban1a+ @ ml, se&in--a ,erbedaan bobo( 1an- (er9adi 'u+u, besar.

F3 @@,9 Q 2,<9 1,@ Q 0 ?,8 Q 0,4@ 19,@0Q 0,80 <3,33Q?,11

F4 <2,12 Q 3,@< 1,@ Q 0 < Q 0,4@ 1?,91 Q 2,04 2@,33Q3,@1

F@ <1,24 Q 3,9? 1,2 Q 2,< ?,? Q 0,@@ 30,83 Q 13,01 3<,?<Q9,29

0esera-aman u+uran ,a('&, meru,a+an sala& sa(u )a+(or ,en(in- un(u+ mem,er+ira+an +andun-an Ea( a+(i) ,er ,a('&. Di&ara,+an (ia, ,a('& men-andun- 10 m- ,ro,ranolol

&idro+lorida. Dari &asil ,en-u+uran dida,a(+an rera(a u+uran ,a('& ;?,9Q0,22= > ;@,<Q0,4@=mm sam,ai den-an ;8Q0= > ;@,8Q0,2<=mm. 0esera-aman u+uran ini, a+an ber+ai(an

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den-an +esera-aman +andun-an bobo( dan +esera-aman Ea( a+(i) 1an- di&asil+an. 0esera-aman+e(ebalan,a('&, mem,en-aru&i +emuda&an dalam ,en--unaan ,a('&. Se,er(i 1an- di9elas+an ole& #a(&io/i(E e( al. ;1999= u+uran +e(ebalan ,a('& bu+al sebai+n1a an(ara 0,@A1,0 mm, a,abila lebi& +e'il a+an men1uli(+an dalam ,ema+aiann1a. asil ,en-u9ian menun9u++an +e(ebalan ,a('& ber+isar an(ara 1,1 mm sam,ai den-an 1,@ mm. 6+uran ini dian--a, (ida+ (erlalu (ebal 1an- membua( ,ema+aian (ida+ n1aman, ser(a (ida+ (erlalu (i,is 1an- a+an men1uli(+an ,ema+aian. 0emam,uan men-emban- sua(u ,a('& meru,a+an sala& sa(u s1ara(dari sua(u sediaan,a('&.#en-emban-n1a,a('& ber+ai(an den-an +emam,uan ma(ri+s dalam mele,as+an oba( dan +ee)e+(i)an ,a('& mele+a( ,ada mu+osa. Pemberian ,erla+uan den-an ,enamba&an PVP ,ada )ormula di&ara,+an da,a( memban(u ,ene(rasi air +e dalam ma(ri+s, se&in--a oba( da,a( dile,as+an dari ma(ri+s ;Pa(el e( al., 200<=. Pen-u+uran +emam,uanmen-emban-sua(u,a('& di-una+an ,arame(er 1an- disebu( s/ellininde>.Parame(er(ersebu(meru,a+an ,ersen(ase an(ara bera( sebelum ,erla+uan den-an bera( se(ela& ,erla+uan. 0emam,uan men-emban- ;s/ellininde>=Sodium$#$seba-ai,olimer mu+oad&esi), di,en-aru&i ole& , . Sodium $#$ (ermasu+ -olon-an anioni+ bioad&esi) ,olimer,-olon-an(ersebu(mam,u men-emban- di mu+osa usus ,ada , se+i(ar < ;4ern+o,AS'&nur'& e( al., 2000=. al ini men-a+iba(+an ,a('& 1an- di&asil+an mam,u men-emban-dan(er9adi,erbedaan +emam,uan men-emban- ;s/ellin- inde>= ,ada se(ia, )ormula. Penamba&an PVP men1ebab+an,enin-+a(an+emam,uan men-emban- sodium $#$ dalam ,a('&. F2 mem,un1ai inde+s ,en-emban-an ,alinba-us, nai+ 4 +ali li,a( dibandin-+an ,la'ebo, dan &am,ir 3 +ali li,a( dibandin-an F1 1an(an,a ,enamba&an PVP. PVP memili+i +emam,uan menin-+a(+an ,en-emban-an sodium $#$ ser(a menin-+a(+an elas(isi(as dan ,emben(u+an )ilm ,ada ,a('& ;Na)ee e( al., 2003M Pa(el e( al., 200<=. 69i/a+(umu+oad&esiadala& ,en-u+uran sebera,a lama ,a('& mu+oad&esi) 1an- di&asil+an mem,un1ai +emam,uan menem,el ,ada mu+osa. #u+oad&esi da,a( dide)inisi+an seba-ai ,erle+a(an an(ara ,olimer dan mu+osa. Se'ara umum mu+oad&esi (erba-i dalam (i-a (a&a,an 1ai(u ,embasa&an, in(er,ene(rasi dan me+anisme ,en-un'ian an(ara ,olimer dan mu+osa. 0ele+a(an /a+(u mu+oad&esi da,a( di,en-aru&i ole& bebera,a

)a+(or an(ara lain massa mole+ul dari ,olimer, /a+(u +on(a+ an(ara ,olimer dan mu+osa, ra(aA ra(a inde+s ,en-emban-an ,olimer dan membran biolo-i 1an- di-una+an ;Pa(el e( al., 200<=. Sodium $#$ di+enal seba-ai basis mem,un1ai da1a le+a( (in--i (er&ada, mu+osa, ber+ai(an den-an i(u ,enamba&an ,erla+uan den-an PVP di&ara,+an da,a( mem,er'e,a( ,ele,asan oba( ,ada ma(ri+s +arena adan1a ,ene(rasi air 1an- masu+. *u9uan dari ,erla+uan(ersebu(di&ara,+anda,a( mem,en-aru&i+ee)e+(i)an/a+(ule+a( ,a('&.Seba-ai,erbandin-an,/a+(u mu+oad&esi ,olimer sodium $#$ ,ada mu+osa usus , < dida,a(+an /a+(u 2,0Q0,3 9am ;Hrabo:a' e( al, 200@=. 4erdasar+an *abel 2,(erli&a( ba&/a ,enamba&an +onsen(rasi PVP mem,en-aru&i +ele+a(an /a+(u mu+oad&esi. 4erdasar+an ,er&i(un-an s(a(is(i+a !N!V! sa(u 9alan, (erli&a( ,erbedaan 1an- si-ni)i+an ,ada /a+(u mu+oad&esi. Perbedaan +ele+a(an /a+(u mu+oad&esi ,ada ,lasebo den-an F1 dia+iba(+an adan1a ,enamba&an ,ro,ranolol &idro+lorida ,ada F1, &al inila& 1anmen1ebab+an (er9adin1a ,enurunan /a+(u mu+oad&esi ,ada F1. Penurunan /a+(u mu+oad&esi 9u-a (erli&a( ,ada ,lasebo dibandin-+an den-an F2 sam,ai den-an F@. al(ersebu(dia+iba(+an,enamba&an ,ro,ranolol &idro+lorida dan PVP ,ada F2 sam,ai den-an F@. 4erdasar+an &asil (ersebu(, ,lasebo 1an- &an1a men-andun- sodium $#$ mem,un1ai /a+(u mu+oad&esi 1an- lebi& ba-us 9i+a dibandin-+an den-an sodium $#$ 1an-(ela&menda,a(+an,enamba&an ,ro,ranolol &idro+lorida dan PVP. asil ,eneli(ian ini se9alan den-an &asil ,eneli(ian Pa(el e( al. ;200<= ,eneli(ian (ersebu( menun9u++an 9i+a ,olimer '&i(osan da1a le+a(n1a (urun se(ela& menda,a( ,enamba&an PVP. asil u9i /a+(u mu+oad&esi menun9u++an sodium $#$ mem,un1ai da1a le+a( 1an,alin- lama, &al ini se,er(i 1an- diun-+a,+an ole& 4ern+o,AS'&nRr'& dan Hreimel ;200@= 9i+a (urunan+arbo&idra(se,er(i +arbo+sime(ilselulosa dan '&i(osan mem,un1ai da1a le+a( 1an- (in--i seba-ai ,olimer mu+oad&esi). #enuru( 4ern+o,AS'&nRr'& e( al. ;2000=, )a+(orA)a+(or 1an- mam,u mem,en-aru&i +ele+a(an /a+(u mu+oad&esi ,ada sua(u ,olimer mu+oad&esi) adala& +emam,uan men-emban- sua(u ,a('&, me+anisme i+a(an, +ara+(eris(i+ mu+osa dan da1a le+a(. 0ele+a(an Sodium $#$ sela+u ,olimer mu+oad&esi) anioni+ da,a( di9elas+an den-an (eori ele+(ron 1an- disam,ai+an ole& Jas(i e( al. ;2003=, ,ada ,ermu+aan sediaan mu+oad&esi) (erda,a( 2 la,isan ele+(ri+ se&in--a (er9adi ,roses (rans)er

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ele+(ron an(ara mu+oad&esi) ,olimer dan 9arin-an -li+o,ro(ein ,ada musin. Selain &al (ersebu(, (er9adi 9u-a i+a(an se+under ,ada sis(em mu+oad&esi), 1ai(u adan1a i+a(an :an der /alls dan i+a(an &idro-en 1an- (erben(u+. 4erdasar+an (eori (ersebu(, ,erbedaan /a+(u le+a( an(ara ,lasebo den-an )ormula lainn1a +emun-+inan disebab+an adan1a ,en-aru& PVP (er&ada, (rans)er ele+(ron 1an- (er9adi. al ini a+an ber,en-aru& +e,ada ,enurunan +emam,uan ,en-un'ian an(ara ,olimer dan mu+osa, se&in--a men1ebab+an ,enurunan ,ada +emam,uan le+a( Sodium $#$ sela+u ,olimer mu+oad&esi). 69i , ,ermu+aan ,a('& dila+u+an un(u+ men-e(a&ui , dari ,a('& 1an- di&asil+an. , ,a('& 1an- di&asil+an &arus mem,un1ai , 1an- ne(ral, se&in--a (ida+ berba&a1a ;iri(asi= a,abila di-una+an ,ada mu+osa manusia. , 1an- di&asil+an 9u-a a+an mem,en-aru&i +emam,uan men-emban- ;s/ellin- inde>= ,ada ,olimer mu+oad&esi). Sodium $#$ sela+u,olimermu+oad&esi),(ermasu+ -olon-an ,olimer bioad&esi) anioni+ 1anmem,un1ai+emam,uanmen-emban;s/ellin- inde>= ma+simal ,ada , se+i(ar <;4ern+o,AS'&nur'& e( al., 2000=. 4erdasar+an &asil ,eneli(ian, (erli&a( (ida+ ada ,erbedaan , ,ermu+aan se'ara si-ni)i+an. Semua )ormula menun9u++an , 1an- sama 1ai(u an(ara ? sam,ai den-an <. Polimer anioni+ mem,un1ai +emam,uan men-emban- ,ada , se+i(ar < +arena ,ada , 1an- renda&, +on)ormasi mole+ulAmole+ul Sodium $#$ a+an salin-

(eri+a( dan men--um,al a+iba( adan1a i+a(an &idro-en ;Hrabo:a' e( al., 200@=. 69i Pele,asan Pro,ranolol $l dari Pa('& 4u+al #u+oad&esi) Penen(uan +ur:a ba+u ,ro,ranolol $l dalam bu)er )os)a( iso(onis , ?,8dila+u+an den-an membua( sua(u seri +adar ,ro,ranolol $l dalam laru(an bu)er )os)a( iso(onis , ?,8, +emudiandiu+ursera,ann1aden-an s,e+(ro)o(ome(er 6V ,ada ,an9an- -elombansera,an ma+simum 28? nm. 0ur:a ba+u di,erole& dari &ubun-an an(ara +adar dan sera,an. asil ,er'obaan menun9u++an +ur:a ba+u ,ro,ranolol $l men-i+u(i ,ersamaan -aris re-resi linier 3S 0,1@2O T 0,1?9 den-an nilai r sebesar 0,99<. Da(a ini di-una+an un(u+ ,ene(a,an +adar ,ro,ranolol $l 1an(erdisolusi. Disolusi dide)inisi+an seba-ai ,roses melaru(+an sua(u oba( dari sediaan ,ada( dalam medium (er(en(u. 69i disolusi dila+u+an un(u+ men-e(a&ui ,ro)il ,ele,asan ,ro,ranolol $l dari ,a('& mu+oad&esi) ,ro,ranolol $l. 69i dila+u+an ,ada su&u medium 3<P$ dan medium disolusin1a beru,a bu)er )os)a( iso(onis , ?,8. 4an1a+n1a ,ro,ranolol $l (erdisolusi dibua( ,lo( &ubun-an den-an /a+(u se&in--a memben(u+ +ur:a an(ara ,ro,ranolol $l (erdisolusi seba-ai )un-si /a+(u se,er(i 1an(erli&a( ,ada Hambar 1.

140 120 100 K (erdisolusi 80 ?0 40 20 0 0 100 200 7a+(u ;meni(= F1 F2 F3 F4 F@ 300 400

Hambar 1A 0ur:a ubun-an 7a+(u den-an 0adar Pro,ranolol $l *erdisolusi

Dari ,er&i(un-an Dissolu(ion 5))i'ien'1 ;D5=3?0 di+e(a&ui 9i+a, ,ele,asan oba( ,alinbai+dida,a(+an,adaF21ai(u ;<4,4@<Q3,919=K. 0emam,uan mele,as+an oba( ber+ai(an den-an +emam,uan ,a('& dalam men-emban-. Sema+in besar an-+a s/ellin-inde>1an- di&asil+an, ma+a

dimun-+in+an ,ro)il ,ele,asan oba( a+an menun9u++an ,ro)il 1an- ba-us. Inde+s ,en-emban-an, ,ada F2 den-an ,erbandin-an Sodium $#$.PVP ;9@0 m-.@0 m-= dida,a(+an &asil inde+s ,en-emban-an 1an- ,alin- ba-us. Se,er(i 1an- diun-+a,+an ole& Pa(el e( al. ;200<= 9i+a inde+s ,en-emban-an oba(

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berbandin- lurus den-an ,ele,asan oba(n1a.Sema+inba-usinde+s ,en-emban-an sua(u ,a('&, ma+a a+an sema+in ba-us ,ula ,ro)il ,ele,asan oba(n1a. F1 mem,un1ai ,ele,asan oba( 1anlebi& bai+ 9i+a dibandin-+an den-an F3, F4 dan F@ dia+iba(+an +arena +emuda&an le,asn1a ,ro,ranolol&idro+loridadaribasisn1a, men-in-a( ,ro,ranolol &idro+lorida muda& laru( den-an air. Pada F2 mem,un1ai +emam,uan ,ele,asan oba( lebi& bai+ dari,ada F1 +arena adan1a ,enamba&an PVP sebesar @0 m-. Penamba&an PVP inila& 1an- memban(u ,en-emban-an ,a('& ,ada F2 se&in--a oba( lebi& muda& (erle,as dari oba(n1a. Namun, sema+in (in--i +adar PVP 1an- diberi+an sema+in renda& ,ula nilai D53?0. al ini disebab+an +arena (er9adin1a i+a(an silan;'ross lin+= an(ara Sodium $#$ den-an PVP. #e+anisme(er9adin1ai+a(an(ersebu( di+arena+an si)a( Sodium $#$ +e(i+a laru( dalam air den-an PVP memben(u+ &idro-el dan mem,ersem,i( ron--a 1an- ada ,ada basis, se&in--a men-&alan-i ,ele,asan oba( ,ada basisn1a. idro-el 1an- (erben(u+ an(ara Sodium $#$ dan PVP men1ebab+an ,eruba&an si)a( 1an- men1ebab+an (ida+ laru( ,ada air. al inila& 1an- men1ebab+an ,ele,asan oba( ,ada ,a('& (er9adi den-an sis(em sus(ained release ;le,as lamba(=. al ini se9alan den-an 1an- diun-+a,+an ole& S9o&aei ;1998=, ba&/a ,olimer 1an- bersi)a( &idro)ili+ mem,un1ai +emam,uan men-emban- ,ada medium 'air, normaln1a ,olimer (ersebu( a+an

beruba& men9adi &idro-el +arena adan1a i+a(an silan- ;'ross lin+= se&in--a men1ebab+an ma(ri+sn1a men9adi (ida+ laru( dalam medium namun &an1a men1era, air sa9a. 05SI#P6G!N 1. Pa('&1an-di&asil+anmenun9u++an +esera-aman bobo( dan u+uran. , ,a('& ber+isar an(ara ?,?A<, se&in--a (ida+ a+an men1ebab+an iri(asi ,ada ron--a mulu(. Penamba&anPVP,men1ebab+an ,enin-+a(an +emam,uan men-embansodium$#$&in--a3+alili,a(. Penamba&an ,ro,ranolol &idro+lorida dan PVP menurun+an +emam,uan mele+a( ,olimer mu+oad&esi) sodium $#$. 2. asil u9idisolusi menun9u++an ,enamba&an PVP 1an- sema+in besar 'enderunmem,erlama ,ele,asan oba(. Penamba&an PVP sebesar @0 m- men1ebab+an ,ro)il ,ele,asan oba( 1an- ,alin- (in--i.

S!"!N Perludila+u+anu9i,ele,asan ,ro,ranolol $l dari ,a('& mu+oad&esi) se'ara in :i:o ,ada &e/an u9i. 6$!P!N *5"I#! 0!SI *erima+asi& +e,ada DIP! 0%P5"*IS 7ila1a& VI 1an- memberi+an dana ,eneli(ian melalui Pro-ram Peneli(ian Dosen #uda ;u9i disolusi= dan GPP# 6#S 1an- memberi+an dana ,eneli(ian melalui Pro-ram Peneli(ian "e-uler ;u9i si)a( )isi+=.

D!F*!" P6S*!0! !nonim, 19<9, Farma+o,e Indonesia, 5disi III, De,ar(emen 0ese&a(an "e,ubli+ Indonesia, Ja+ar(a. !nonim, 200<, Inderal ;online=, &((,.LL///.r>lis(.'omL'-iL-eneri'L,ro,ran.&(m, dia+ses ? 9anuari 200<. 4ern+o,AS'&nRr'&, !., and Hil-e, 4., 2000, !nioni' #u'oad&esi:e Pol1mer as !u>iliar1 !-en(s )or Peroral !dminis(ra(ion o) ;Pol1=Pe,(ide Dru-s.In)luen'e o) Has(ri' Jui'e, Dru- De:elo,men( and Indus(rial P&arma'1, 2?;2=, 108A111. 4ern+o,AS'&nRr'&, !., and Hreimel, !., 200@, *&iomers . *&e Ne>( Henera(ion o) #u'oad&esi:e Pol1mers, !m J Dru- Deli:, 3;3=, 143. 4ern+o,AS'&nRr'&, !., and S(einin-er S., 2000, S1n(&esis and $&ara'(eriEa(ion o) #u'oad&esi) *&iola(ed Pol1mers. In(erna(ional Journal o) P&arma'eu(i's, 194, 240. 4ra'&(, S., 200<, *ransdermal *&erau,e(i' S1s(em. ! "e:ie/, Inno:a(ion in P&arma'eu(i'al *e'&nolo-1, ;online= ///.i,(online.'omLar(i'lesL,ubli', 92A98, dia+ses 2 Januari 2008. Hrabo:a', V., Hu--i, D., 4ern+o,AS'&nRr'&, !., 200@, $om,arison o) (&e #u'oad&esi:e Pro,er(ies o) Various Pol1mers, !d:an'e Dru- Deli:er1 "e:ie/s, @<, 1<1<. an-o, "., 0a:imani, S., #ullai'&aram, !."., and Ja1a+ar, 4., 199<, In Vi(ro S(udies on 4u''al S(ri,s o) Hliben'lamide 6sin- $&i(osan, Ind. J. P&arm. S'i., @9. 23223@.

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arris, D. and "obinson, J."., 1992, Dru- Deli:er1 Via (&e #u'ous #embranes o) (&e %ral $a:i(1, J. P&arm. S'i., 81.1A10. #a(&io/i(E, 5., $&i'+erin-, D.5., Ge&r, $.#., 1999, 4ioad&esi:e Dru- Deli:er1 Sis(ems. Fundamen(als, No:el !,,roa'&es and , Vol.98, @44, $"$ Press.7as&in-(on. Na)ee, N.!., Ismail, F.!., 4oraie, N.!., and #or(ada, #.G., 2003, #u'oad&esi:e 4u''al Pa('&es o) #i'onaEole Ni(ra(e. In Vi(roLIn Vi:o Per)orman'e !nd 5))e'( o) !-ein-, In(erna(ional Journal o) P&arma'eu(i's, 2?4;1A2=.1A14. Nair, #.#., and $&ien, 3.7., 199?, De:elo,men( o) !n(i'andidal Deli:er1 S1s(ems. ;II= #u'oad&esi:e De:i'es For Prolon-ed Dru- Deli:er1 In *&e %ral $a:i(1, Dru- De:. Ind. P&arm., 22. 2432@3. Narendra, $., Srina(&, #.S., Pra+as&rao, 4., 200@, De:elo,men( o) *&ree Ga1ered 4u''al $om,a'( $on(ainin- #e(o,rolol *ar(ra( b1 S(a(is(i'al %,(imiEa(ion *e'&niFue, In(erna(ional Journal o) P&arma'eu(i's, 304.102A114. Nori+o, N., #i+i., 0aEu1a, 0., 3asus&i, N., 0en9i, %., and "1oEo, %., 199?, %,(imiEinPre,ara(ion *e'&ni's o) Sodium $arbo>1lme(&1l $ellulose #u'ila-e b1 %r(&o-onal *es(, Journal o) (&e Ni,,on os,i(al P&arma'is( !sso'ia(ion, 22;4=.409A41@. Pa(el, V.#., 4ra9a,a(i, 4.H., and Pa(el, #.#., 200<, Desi-n !nd $&ara'(eriEa(ion o) $&i(osanA $on(ainin- #u'oad&esi:e 4u''al Pa('&es o) Pro,ranolol 1dro'&loride, !'(a P&arm., @<. ?1<2. S&ar-el, G., 7uAPon-, S., and 3u, !.4.$., 200@, !,,lied 4io,&arma'eu(i's and P&arma'o+ine(i's, Fi)(& 5di(ion, #' Hra/ ill, Sin-a,ura. S&in, S.$., 4um, J.P. and $&oi, J.S., 2000, 5n&an'ed 4ioa:ailabili(1 b1 4u''al !dminis(ra(ion o) *riam'inolone !'e(onide )rom (&e 4ioad&esi:e Hels in "abbi(s, In(. J. P&arm. 209.3<43. S9o&aei, !. ., 1998, 4u''al #u'osa !s ! "ou(e For S1s(emi' Dru- Deli:er1. ! "e:ie/, J P&arm P&arma'eu( S'i, 1;1=, 22 7ani, #.S., 200<, $urren( S(a(us in 4u''al Dru- Deli:er1 S1s(em ;online=, ///.,&armain)o.ne(Lre:ie/sL'urren(As(a(usAbu''alAdru-Adeli:er1As1s(em, dia+ses 4 Januari 200<.

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