pembuatan ekstraksi

8/18/2019 pembuatan ekstraksi

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PEMBUATAN EKSTRAK

Indah Yulia Ningsih, S.Farm., M.Farm., Apt.


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TOPIK KULIAHBAHAN BAKU SEDIAAN FITOFARMASI :

• SIMPLISIA

– Pembuatan simplisia

– Kontol !ualitas simplisia

• EKSTRAK

– Pemuatan e!stra!

– K"ntr"l !ualitas e!stra!


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MATERI KU#IA$

PEMBUATAN EKSTRAK:

• Pen"a#uluan

•

De$inisi e!sta!KONTROL KUALITAS EKSTRAK


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Du% "e&elopment $om Me"i'inal Plants

Traditional medicine

Selected medicinal plants

Crude drug

Extract

Standardized extract

Phytomedicines

Phytotherapy

Early sreening

Extraction

Pre clinical test &

standardization

Clinical test

Isolate

I s o l a t

i o n

Single compound

Pre clinical test

Active compound

Pharmacotherapy

Structure modification

Isolation

Clinical test


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Salix alba (Willow tree)

Isolasi untu! $ama!oteapi

(Kar, 2007)


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Sen(a)a a!ti$ tun%%al &s e!sta!

• E!sta! &aleiana : &altat*

"i#i"o&altat* asam &aleenat*

&aleenon→ e$e! se"ati$+

• Sen(a)a in"i&i"ual ti"a! memili!i

e$e! se"ati$→ !emun%!inan

sine%isme


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Reasons $o not isolatin%

• E,ta'ts !no)n to 'ontain a an%e o$simila a'ti&e 'ompoun"s* )it# )ell

"o'umente" 'lini'al a'ti&it( $o )#ole osemi-pui$ie" e,ta't

• Unsue o$ a'ti&e 'onstituents e&en i$some '#emist( !no)n

• A'ti&es !no)n o suspe'te" to beunstable

• S(ne%( o anta%onism


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P#(tome"i'ines

• ae me"i'inal po"u'ts t#at 'ontain

plant mateials as t#ei

p#ama'olo%i'all( a'ti&e 'omponent.

• /u"e "u% 0"ie" #eb1 o )#ole

e,ta't "ei&e" $om it is 'onsi"ee"

to be t#e a'ti&e in%e"ient.

• /omple, mi,tues o$ 'ompoun"s t#at

%eneall( "on2t e,et ston%*

imme"iate e$$e't.


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De$inisi E!sta!

F.U. I% Ed. &Italian Pharma'"p"eia(

• E,ta'ts ae li3ui" 0$lui" e,ta'ts1 o

soli" 0"( e,ta'ts1 o o$ inteme"iate'onsisten'( 0so$t e,ta'ts1

pepaations obtaine" $om

&e%etable a) mateials* as a ule

"ie" 0"u%s1.


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De$inisi E!sta!

• E,ta'ts ae pepae" b( e,#austion

e,ta'tion )it# appopiate sol&ents* t#ou%#

ma'eation o pe'olation* o ot#e suitable

po'e"ues* $om "u%s e"u'e" toappopiate pati'le si4e

• In some 'ases t#e "u%s to be e,ta'te"

must un"e%o pelimina( teatment 0$o

e,ample : ina'ti&ation o$ en4(mes* "e$attin%1

• In ot#e 'ases un)ante" matte is emo&e"

a$te e,ta'tion


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5ualit( /ontol o$ e,ta'ts

• 5/ o$ #ebal mateials – Me"i'inal plant aut#enti'ation

•

Po"u'tion met#o"s – Total e,ta't

– Pui$ie" e,ta't

•

A"6ustment o$ 5ualit( – 5ualitati&e 7 3uantitati&e

stan"a"i4ation

– E,ta't Re%ulation


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5/ o$ #ebal mateials

Me"i'inal plant aut#enti'ation:

• Ma'os'opi' 7 mi'os'opi'

•

/#omato%ap#i' $in%epint• Potein po$ilin%

• DNA po$ilin%


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Pr"du'ti"n Meth"d

T)o main %oups o$ e,ta'ts :

8. Total e,ta'ts 0e!sta! total1

9. Pui$ie" e,ta'ts 0e!sta!tepui$i!asi1

(Bonati, 1991)


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Total e,ta'ts

• Total o ta"itional e,ta'ts ae e,ta'ts

t#at 'ontain all t#e e,ta'ti&e matte

obtaine" b( teatin% t#e "u% )it# a

sol&ent* as a ule a3ueous o #("o

al'o#oli'

• Ta"itional e,ta'ts ma( be "i&i"e"

into $lui" e,ta'ts* so$t e,ta'ts* an"

"( e,ta'ts

(Bonati, 1991)


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Pui$ie" e,ta'ts

• Pepaations $om )#i'# substan'es

'onsi"ee" useless i$ not a'tuall(

"etimental to t#e a'ti&it( o$ t#e e,ta't#a&e been emo&e"

• A pui$ie" e,ta't ma( be obtaine" b(

e,ta'tin% t#e "u% )it# a sele'ti&e

sol&ent an"o b( emo&in% t#e inet

substan'es b( &aious met#o"s a$te t#e

pima( e,ta'tion(Bonati, 1991)


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Pui$ie" e,ta'ts

• Pepaations o$ a pui$ie" e,ta't must bepe'e"e" b( 'on$imation t#at t#e a'ti&it(o$ t#e "u% is 'onse&e"+ total e,ta'tso$ten 'ontain substan'es su'# assaponins an" pol(p#enols t#at aee%a"e" as inet but t#at ma( be 'u'ialto t#e absoption o$ t#e a'ti&e pin'iples

• ;e #a&e to be sue t#at t#is popet( #asnot been lost in t#e pui$ie" e,ta'ts<


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Pui$ie" e,ta'ts

Fe) e,amples o$ pui$ie" e,ta't :

• E,ta'ts o$ Senna )it# a => to ?@

'ontent o$ sennosi"es• E,ta'ts o$ Fan%ula )it# a 9@ to 9>

'ontent o$ #("o,(ant#a'enes


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A"6ustment o$ 5ualit(

Tests t#at essential $o e,ta'ts :

• P#(si'al '#aa'teisti's

•

5ualitati&e 7 3uantitati&estan"a"i4ation* potential

impuities

•

Total aeobi' mi'obial 'ount


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A"6ustment o$ 5ualit(

P#(si'al '#aa'teisti's

• Ta"itional testin% : appeaan'e* pH*

solubilit(* total soli"s* as#• Detemination o$ solubilit( o$ so$t 7

"( e,ta'ts

•

Pati'le si4e o$ "( e,ta'ts→

"ie't'ompession tablet


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)ualitati*e standardi+ati"n

• /#omato%ap#i' patten$in%epint → e,'lu"e a"ulteant

• Not onl( $o sin%le po"u'ts o $amil( o$po"u'ts* but s#oul" e,ten" to se&ealsubstan'es o %oups o$ substan'es

E, : e,ta't o$ bol"o 0Peumus boldus1'alls $o t#e i"enti$i'ation o$ bol"ine*total al!aloi"s 7 $la&onoi"s


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• 5ualitati&e stan"a"i4ation is

essential 'omplement $o

3uantitati&e stan"a"i4ation o$'#aa'teisti' a'ti&e pin'iples

)#en no spe'i$i' assa(s ae as

(et a&ailable


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• T#e pesen'e o$ se&eal po"u'ts o$ li!e

stu'tue in an e,ta't o$ten

ne'essitates %lobal 'oloimeti' ospe'top#otometi' "etemination

e, : total al!aloi"s* total $la&onoi"s* et'.

0See Mono%a$i E!sta! Tumbu#an In"onesia$o t#e "etails1


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Total aeobi' mi'obial 'ount• No Pat#o%en allo)e"

• Total ba'teial 'ount: 8@-8@=% o ml

'an be a'#ie&e"


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Etra't Regulati"n

• T#e a"6ustment o$ p#(top#ama'euti'alpepaation to a 'etain a'ti&e substan'e'ontent

•

E,ta't is e%a"e" as t#e a'ti&e 'omponento$ a me"i'ine "esi%nate" as ap#ama'euti'al $omulation* not an in"i&i"ualsubstan'e 'ontaine" in it

•

Oi%inal atio o$ a'ti&e substan'es ispese&e" )it#in a''eptable limits

(List & Schmidt,

1989)


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Drug with standard

content

Drug with lower

content

Drug with too high

content

Liquid extract too

weak

Liquid extract too

strong

Extract too

weak

Extract too

strong

Mixed & adjusted

Regulated

Extracts

Liquid mixture

adjusted

(List & Schmidt, 1989)


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A""in% t#e inet a"6u&ant

8. T#e mis'ella is e&apoate" "o)n to at#in e,ta't un"e t#e 'ae$ul 'on"ition

%i&en in t#e pati'ula P#ama'opoeia7 t#is e,ta't bot# is t#en )ei%#e".T#e "( esi"ue 7 t#e a'ti&esubstan'e 'ontent o$ ali3uot potions

o$ it ae "etemine". T#e t#in e,ta't ist#en a"6uste" to t#e e3uie" 3uantit(o$ "e,tin o la'tose


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08@@ C R 1 a

, ---------------- - T

b

a )ei%#t o$ a'ti&e substan'e 0%1 in t#e e,ta't bot#

b e3uie" 'ontent o$ a'ti&e substan'es in "( e,ta't

01

R pemitte" esi"ual moistue in "( e,ta't 01T )ei%#t o$ t#e "( esi"ue o$ t#e total e,ta't bot#

0%1

, )ei%#t o$ a"6u&ant substan'es to be a""e" 0%1



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9. T#e mis'ella is e&apoate" to "(ness+i$ onl( small 3uantit( o$ it ae a&ailable

it is %oun" )it# t#e e3uie" 3uantit(o$ a"6u&ant substan'e. ;#en la%ete'#ni'al 3uantities ae bein%po'esse"* t#e "( e,ta't* %oun" as

$ine as possible* must be mi,e"#omo%enousl( )it# t#e 'al'ulate"3uantit( o$ a"6u&ant substan'e insuitable mi,es


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TEKNOLOIEKSTRAKSI

TUMBUHAN OBAT


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Pen-iapan ahan a!u

sediaan Fit"armasi• Budida-a tumuhan "at

•

Te!n"l"gi pas!a panen• Te!n"l"gi e!stra!si


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E,ta'tion

• E,ta'tion* as t#e tem is use"

p#ama'euti'all(* in&ol&es t#e

sepaation o$ me"i'inall( a'ti&e potionso$ plant o animal tissues $om t#e

ina'ti&e o inet 'omponents b( usin%

sele'ti&e sol&ents in stan"a" e,ta'tionpo'e"ues


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T#e pin'iple o$ soli"-li3ui" e,ta'tion

• ;#en a soli" mateial 'omes in 'onta't )it# asol&ent* t#e soluble 'omponents in t#e soli"mateial mo&e to t#e sol&ent.

• T#us* sol&ent e,ta'tion o$ plant mateial esults in

t#e mass tans$e o$ soluble a'ti&e pin'iple0me"i'inal in%e"ient1 to t#e sol&ent* an" t#is ta!espla'e in a 'on'entation %a"ient.

• T#e ate o$ mass tans$e "e'eases as t#e'on'entation o$ a'ti&e pin'iple in t#e sol&ent

in'eases* until e3uilibium is ea'#e"* i.e. t#e'on'entations o$ a'ti&e pin'iple in t#e soli"mateial an" t#e sol&ent ae t#e same.


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T#e pin'iple o$ soli"-li3ui" e,ta'tion

• T#eea$te* t#ee )ill no lon%e be a masstans$e o$ t#e a'ti&e pin'iple $om plantmateial to t#e sol&ent.

• Sin'e mass tans$e o$ t#e a'ti&e pin'iple

also "epen"s on its solubilit( in t#e sol&ent*#eatin% t#e sol&ent 'an en#an'es t#e masstans$e.

• Moeo&e* i$ t#e sol&ent in e3uilibium )it#

t#e plant mateial is epla'e" )it# $es#sol&ent* t#e 'on'entation %a"ient is'#an%e". T#is %i&es ise to "i$$eent t(pes o$e,ta'tions: 'ol" pe'olation* #ot pe'olationan" ma'eation


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Plant Po"u'ts

• Impure liquids• Semisolids• Powders

Decoctions Infusions

Fluid extracts

Tinctures

Pilular (semisolid) extracts

Powdered extracts


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Stan"a"i4e" e,ta'tion po'e"ues

• to attain t#e t#eapeuti'all( "esie"

potion an" to eliminate t#e inet

mateial b( teatment )it# a sele'ti&esol&ent !no)n as menstruum


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Stan"a"i4e" e,ta'tion po'e"ues

Medicinal Herbs

Fractions Tinctures

Fluid extracts

Isolate

Extracts

Drug


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eneal Met#o"s o$ E,ta'tion

• Ma'eation

• In$usion

• De'o'tion• Di%estion

• Pe'olation

• Hot /ontinuous E,ta'tion 0So,#let1• A3ueous Al'o#oli' E,ta'tion b(

Fementation


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eneal Met#o"s o$ E,ta'tion

• /ounte-'uent E,ta'tion

• Ultasoun" E,ta'tion 0Soni'ation1

• Supe'iti'al Flui" E,ta'tion

• P#(toni's Po'ess


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A3ueous Al'o#oli' E,ta'tion b(

Fementation• Soa!in% t#e 'u"e "u%* in t#e $om o$ eit#e

a po)"e o a "e'o'tion 0kasaya1* $o aspe'i$ie" peio" o$ time* "uin% )#i'# itun"e%oes $ementation an" %eneatesal'o#ol in situ+ t#is $a'ilitates t#e e,ta'tion o$t#e a'ti&e 'onstituents 'ontaine" in t#e plantmateial.

• T#e al'o#ol t#us %eneate" also se&es as apese&ati&e

• A(u&e"i' pepaation : karpurasava,kanakasava, dasmularista


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/ounte-'uent E,ta'tion 0//E1

•

;et a) mateial is pul&ei4e" usin% toot#e" "is'"isinte%atos to po"u'e a $ine slu(• T#e mateial to be e,ta'te" is mo&e" in one

"ie'tion 0%eneall( in t#e $om o$ a $ine slu(1 )it#ina '(lin"i'al e,ta'to )#ee it 'omes in 'onta't )it#e,ta'tion sol&ent.

• T#e $ut#e t#e statin% mateial mo&es* t#e moe'on'entate" t#e e,ta't be'omes.

• /omplete e,ta'tion is t#us possible )#en t#e3uantities o$ sol&ent an" mateial an" t#ei $lo) atesae optimi4e".


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/ounte-'uent E,ta'tion 0//E1

Ad*antages /i. A unit 3uantit( o$ t#e plant mateial 'an be

e,ta'te" )it# mu'# smalle &olume o$ sol&ent as'ompae" to ot#e met#o"s li!e ma'eation*"e'o'tion* pe'olation.

ii. //E is 'ommonl( "one at oom tempeatue*)#i'# spaes t#e t#emolabile 'onstituents $ome,posue to #eat )#i'# is emplo(e" in most ot#ete'#ni3ues.

iii. As t#e pul&ei4ation o$ t#e "u% is "one un"e )et'on"itions* t#e #eat %eneate" "uin% 'omminutionis neutali4e" b( )ate.

i&. T#e e,ta'tion po'e"ue #as been ate" to bemoe e$$i'ient an" e$$e'ti&e t#an 'ontinuous #ote,ta'tion.


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Ultasoun" E,ta'tion 0Soni'ation1

• T#e use o$ ultasoun" )it# $e3uen'ies

an%in% $om 9@-9@@@ !H4+ t#is in'eases t#e

pemeabilit( o$ 'ell )alls an" po"u'es'a&itation.• One "isa"&anta%e o$ t#e po'e"ue is t#e o''asional

but !no)n "eleteious e$$e't o$ ultasoun" ene%(

0moe t#an 9@ !H41 on t#e a'ti&e 'onstituents o$

me"i'inal plants t#ou%# $omation o$ $ee a"i'als

an" 'onse3uentl( un"esiable '#an%es in t#e "u%

mole'ules.


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Supe'iti'al Flui" E,ta'tion

• E,ta'tion usin% /O9 at 'iti'al point

• O%ani' sol&ents ae $e3uentl( a""e"

to /O9 e,ta'tin% $lui" to alle&iate t#e

polait( limitations

• eneall(* '(lin"i'al e,ta'tion &essels

ae use" $o SFE


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Supe'iti'al Flui" E,ta'tion

A"&anta%es :

i. T#e e,ta'tion o$ 'onstituents at lo)

tempeatue* )#i'# sti'tl( a&oi"s"ama%e $om #eat an" some o%ani'

sol&ents.

ii. No sol&ent esi"ues.iii. En&ionmentall( $ien"l( e,ta'tion

po'e"ue.


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P#(toni's Po'ess

• De&elope" 7 patente" b( A"&an'e" P#(toni'sLt" 0Man'#este* UK1

• T#e sol&ent is 8*8*9*9-teta$luooet#ane* bette!no)n as #("o$luoo'abon-8=a 0HF/-8=a1as a epla'ement $o '#loo$luoo'abons0/F/1.

• T#e b.p. o$ t#is sol&ent is -9> /. It is not$lammable o to,i'.

• Unli!e /F/* it "oes not "eplete t#e o4onela(e.

• It #as a &apo pessue o$ >.? ba at ambient

tempeatue.


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P#(toni's Po'ess

A"&anta%es :

• Unli!e ot#e po'esses t#at emplo( #i%#tempeatues* t#e p#(toni's po'ess is 'ool an"%entle an" its po"u'ts ae ne&e "ama%e" b(

e,posue to tempeatues in e,'ess o$ ambient.• No &a'uum stippin% is nee"e" )#i'#* in ot#e

po'esses* lea"s to t#e loss o$ pe'ious &olatiles.

• T#e po'ess is 'aie" out entiel( at neutal pHan"* in t#e absen'e o$ o,(%en* t#e po"u'ts ne&e

su$$e a'i" #("ol(sis "ama%e o o,i"ation.• T#e te'#ni3ue is #i%#l( sele'ti&e* o$$ein% a '#oi'e

o$ opeatin% 'on"itions an" #en'e a '#oi'e o$ en"po"u'ts.


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P#(toni's Po'ess

A"&anta%es :

• It is less t#eatenin% to t#e en&ionment.

• It e3uies a minimum amount o$ ele'ti'al ene%(.

• It eleases no #am$ul emissions into t#e

atmosp#ee an" t#e esultant )aste po"u'ts0spent biomass1 ae inno'uous an" pose noe$$luent "isposal poblems.

• T#e sol&ents use" in t#e te'#ni3ue ae not$lammable* to,i' o o4one "epletin%.

• T#e sol&ents ae 'ompletel( e'('le" )it#in t#es(stem.


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Sele'tin% an Appopiate E,ta'tion

Met#o"

• Aut#enti'ation o$ plant mateial s#oul" be"one be$oe pe$omin% e,ta'tion. An($oei%n matte s#oul" be 'ompletel(eliminate".

• Use t#e i%#t plant pat an"* $o 3ualit( 'ontolpuposes* e'o" t#e a%e o$ plant an" t#etime* season an" pla'e o$ 'olle'tion.


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Sele'tin% an Appopiate E,ta'tion

Met#o"

• /on"itions use" $o "(in% t#e plant mateial

la%el( "epen" on t#e natue o$ its '#emi'al

'onstituents.

•

Hot o 'ol" blo)in% ai $lo) $o "(in% is%eneall( pe$ee".

• I$ a 'u"e "u% )it# #i%# moistue 'ontent is

to be use" $o e,ta'tion* suitable )ei%#t

'oe'tions s#oul" be in'opoate".


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Natue o$ 'onstituents• I$ t#e t#eapeuti' &alue lies in non-pola

'onstituents* a non-pola sol&ent ma( be

use"

e, : lupeol 0Crataeva nurvala1→ #e,ane• I$ t#e t#eapeuti' &alue lies in pola

'onstituents* a pola sol&ent ma( be use"

e, : %l('osi"es 0Bacopa monnieri 7 Centella

asiatica1→ a3ueous met#anol


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Natue o$ 'onstituents• I$ t#e 'onstituents ae t#emolabile*

e,ta'tion met#o"s li!e 'ol" ma'eation*

pe'olation an" //E ae pe$ee".

•

Fo t#emostable 'onstituents* So,#lete,ta'tion 0i$ nona3ueous sol&ents ae use"1

an" "e'o'tion 0i$ )ate is t#e menstuum1

ae use$ul.


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Natue o$ 'onstituents

• /onstituents t#at "e%a"e )#ile bein% !ept in

o%ani' sol&ents : $la&onoi"s an" p#en(l

popanoi"s

• Hi%#e t#an e3uie" tempeatue s#oul" be

a&oi"e". Some %l('osi"es ae li!el( to bea!

upon 'ontinuous e,posue to #i%#e

tempeatue


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Stan"a"i4ation o$ time o$ e,ta'tion

• Insu$$i'ient time means in'omplete e,ta'tion.

• I$ t#e e,ta'tion time is lon%e* un)ante"

'onstituents ma( also be e,ta'te". – I$ tea is boile" $o too lon%* tannins ae

e,ta'te" )#i'# impat astin%en'( to t#e

$inal pepaation.


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E,ta'tion steps

8. Si4e e"u'tion

9. E,ta'tion

. Filtation

=. /on'entation

>. D(in%


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TERIMA KASI$

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