3. Liquid-Liquid Extraction.pdf

8/17/2019 3. Liquid-Liquid Extraction.pdf

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PHARMACEUTICALPHARMACEUTICAL

ANALYSIS ll ANALYSIS ll

LIQUID-LIQUID EXTRACTION


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LIQUID-LIQUID EXTRACTION

ØØ DEFINATIONDEFINATION LiquidLiquid--liquid extraction is aliquid extraction is a

versatile and dependable separationversatile and dependable separation

technique where in an aqueous solution istechnique where in an aqueous solution is

usually brought into contact with anotherusually brought into contact with anotherorganic solvent, exclusively immiscibleorganic solvent, exclusively immiscible

with the former, so as to affect a legitimatewith the former, so as to affect a legitimate

and actual transfer of either one or moreand actual transfer of either one or more

solute into the latter.solute into the latter.


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separation technique is superior separation technique is superior

BecauseBecause

Ø Ease of use

Ø Faster extraction times

Ø Decreased volumes of solvent

Ø Their superior ability to concentrate the

analytes.


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USING METARIALSUSING METARIALS

ØØ Separations may be performed by shaking theSeparations may be performed by shaking thetwo liquids in atwo liquids in a SEPARATORYSEPARATORY FUNNELFUNNEL for afor a

few minutes, and may be extended either tofew minutes, and may be extended either tolarge quantities of pharmaceutical substances orlarge quantities of pharmaceutical substances ortrace levels.trace levels.


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SHOWING BY FLOW CHARTSHOWING BY FLOW CHART

Two liquids placed in separatory funnelTwo liquids placed in separatory funnel

shaken to increase surfaceshaken to increase surface

areaarea

keep some timekeep some time

two phase systemtwo phase system


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FOR ORGANIC &INORGANICFOR ORGANIC &INORGANIC SOLUTESOLUTE

In case of organic soluteIn case of organic solute Two immiscible

organic solvents (e.g; alcohol& ether) are

used instead of aquous organic type of

extraction.In case of inorganic soluteIn case of inorganic solute one aquous

solvent & one organic solvent are

used.But if the component are water

sensitive then we have to form Chelates.


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PRINCIPLESPRINCIPLES

Feed phase

FEED PHASE CONTAINING

SOLUTEThis should be extracted

ADDITION OF SOLVENTIMMICIBLE WITH FEED PHASE

SOME SOLUTESARE TRNSFERED FROM

FEED PHASE TO

SOLVENT PHASE

(1)FEED PHASE

(2)SOLVENT PHASE

After extraction


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AFTER EXTRACTIONAFTER EXTRACTION

THESE TWO PHASES ARE CALLED

These two phases can be separated by

DISTILLATION for their IMMISCIBILITY.liquid-liquid extraction is also applicable

for an organic phase by adding aquous phase

FEED PHASE

RAFFINATE PHASE

OR

R

SOLVENT PHASE

EXTRACT PHASE

E


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THEORYTHEORY

ØØ TheThe NearstNearstDistribution Law!Distribution Law!states that at constantstates that at constanttemperature, a solutetemperature, a solutedistributes itselfdistributes itself

between two immisiblebetween two immisiblesolvents only in asolvents only in aparticular ratio.particular ratio.

KKp = Co/Caqp = Co/CaqKKp=partition coefficientp=partition coefficient

Co=Conc. of the analyte(orgCo=Conc. of the analyte(org))Caq=Conc.of the analyte(aq)Caq=Conc.of the analyte(aq)


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LIMITATIONS

ØØ It is not thermodynamically rigorous. ThatIt is not thermodynamically rigorous. That

means it is solely applicable to very dilutemeans it is solely applicable to very dilute

solutions.solutions.

ØØ It does not hold good when the distributingIt does not hold good when the distributingsubstance encounters association orsubstance encounters association or

distribution in either phases.distribution in either phases.


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TWO ASPECTS OF LIQUIDTWO ASPECTS OF LIQUID--

LIQUID EXTRACTIONLIQUID EXTRACTION

Ø Error due to the volume change

Ø Effectiveness of an extraction


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1. Error due to the volume change: if two

immiscible solvent is under extraction

process, then the volume of the two individualphases will be different comparison to the

initial volumes.

To avoid error of volume change, the

Procedure we adopted is:

Ø Measure the volume of the phase employed

for the analysis and incorporate this volume inthe calculations.


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ØSeparate the phase quantitatively and

subsequently dilute to known volume.ØSeparate the phase quantitatively and make use

of the entire volume in the remaining steps of the

analysis.

ØCarry a maker substance through the extractionto automatically compensate for volume changes.


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INDUSTRIALY EXTRACTIONINDUSTRIALY EXTRACTION


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22.. Effectiveness of an extractionEffectiveness of an extraction:: Based on theBased on the

appropriate partition coefficient of an immiscibleappropriate partition coefficient of an immiscible

solvent pair it is possible to calculate thesolvent pair it is possible to calculate the

effectiveness of an extraction!effectiveness of an extraction!..

Let,Let,

x moles of solute in vx moles of solute in v22 volume when solvent is a!volume when solvent is a!

(x(x--y) moles solute in vy) moles solute in v11 volume when solvent is b!volume when solvent is b!(x(x--y)/ vy)/ v11

Kp=Kp=

y/y/ vv22


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or, Kp =(or, Kp =(x/x/ vv11--x/x/ vv11)) vv22/y/y

or, Kp =x/y.vor, Kp =x/y.v22/v/v11--vv22/v/v11or, Kp =vor, Kp =v22/v/v11(x/y(x/y--11))

or, Kp. vor, Kp. v22/v/v11=(x/y=(x/y--11))

or, x/y= (vor, x/y= (v22

/v/v11

. Kp +. Kp + 11))or, y/x= (vor, y/x= (v11/v/v22. Kp +. Kp + 11) " ) " ## After the total extraction, After the total extraction,

(v(v11/v/v22. Kp +. Kp + 11))f f nn ==

nn


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Here,Here,

KKp = partition coefficientp = partition coefficient

f f nn = fraction of extracted= fraction of extracted


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SOLVENT SELECTION CRITERIASOLVENT SELECTION CRITERIA

11)) MISCIBILITY:MISCIBILITY: Solvents defined as if theSolvents defined as if theTwo components can be mixed together inTwo components can be mixed together in

all proportions without forming two separateall proportions without forming two separate

phases.phases.

Solvent miscible with water in allproportions include Acetone, Acetonitrile,

Dimethyl acetamide, N,N-dimethylformamide,

Dimethyl sulfoxide, 1,4,-dioxane etc.


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22)) DENSITYDENSITY: If density difference is high then: If density difference is high thenimmiscibility will be high. On other hand if densityimmiscibility will be high. On other hand if density

difference is low it causes miscibility.difference is low it causes miscibility.

e.g; He.g; H22O & CHO & CH22ClCl

here the density of CHhere the density of CH22Cl is high.Cl is high.&& HH22O is low.O is low.

So, CHSo, CH22Cl will come down to theCl will come down to the

lower Portion of the separatorylower Portion of the separatory

Funnel &Funnel & HH22O will come up.O will come up.

HH22OO

CHCH22ClCl


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33)) SOLUBILITYSOLUBILITY:: Two immiscible solventTwo immiscible solvent

become totally mixed up under a certain amount.become totally mixed up under a certain amount.

e,g;e,g; HH22O & CHO & CH22ClCl2211..66%% CHCH22ClCl22 = soluable in= soluable in HH22OO

00..2424%% HH22O = soluable in CHO = soluable in CH22ClCl22

To overcome this problem we can use whichTo overcome this problem we can use whichsolubility is zero.Otherwise it would be moresolubility is zero.Otherwise it would be more

complex.complex.


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FACTORS INFLUENCE SOLVENTFACTORS INFLUENCE SOLVENT

EXTRACTIONEXTRACTION

ØØ Effect of temparatureEffect of temparature: Temparature must: Temparature must

be fixed through the process because itbe fixed through the process because it

depends on the solubility of the substancedepends on the solubility of the substance

in two respective solvevts.in two respective solvevts.

KKp = Sp = S11/S/S22

Solubility of solute in solventa!

Solubility of solute in solventa!

Solubility of solute in solvent b! Solubility of solute in solvent b!


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ØØ Effect of pH on extractionEffect of pH on extraction: It may be: It may be

observed that the pH for anobserved that the pH for an extraction system!extraction system!

must be selected in such a fashion so that themust be selected in such a fashion so that themaximum quantity of the analyte is present inmaximum quantity of the analyte is present in

the extractable form, that obviously suggeststhe extractable form, that obviously suggests

that the analyte should always be in the form ofthat the analyte should always be in the form of

either a free base or a free acid.either a free base or a free acid.


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EMULSIONEMULSION

EMULSIONEMULSION:: Emulsion may be defined as aEmulsion may be defined as a

dispersed system containing at least two Idispersed system containing at least two I

mmiscible liquid phases.mmiscible liquid phases.

The effectiveness and meaningful extractionThe effectiveness and meaningful extractionof a solute is rended almost impossibleof a solute is rended almost impossible

when there is an emulsion formation duringwhen there is an emulsion formation during

an extraction process. Emulsion formationan extraction process. Emulsion formation

makes the separation of the two phasesmakes the separation of the two phases

difficult.difficult.


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FACTORS CAUSES SLOWFACTORS CAUSES SLOW--

COALESCENCE EMULSIONCOALESCENCE EMULSION

The breaking of an emulsion could be a slow

process. There are a number of factors

which may be responsible for the slow-

coalescence of an emulsion, namely:1. Finely divided powders of albumin, gelatin

and natural gums have a tendency to coat

droplets formed in an emulsion which

ultimately prevent them from coalescing.


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2. Usually surfactants decrease the interfacial

tension between the two immiscible liquids which

help in stabilizing an emulsion.

3. Ionic species may get absorbed at the interface

of two immiscible layers resulting in the formation

Of a net charge on the droplets. Because all

droplets shall essentially bear the similar charge,

naturally they will repel one another thereby

preventing coalescence.


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In fact,there are many natural and syntheticIn fact,there are many natural and synthetic

substances that are profusely incorporated in thesubstances that are profusely incorporated in the

formulation of drugs which are found to stabilizeformulation of drugs which are found to stabilize

emulsions either by coating the droplets or byemulsions either by coating the droplets or by

minimizing the interfacial tension.Eg;minimizing the interfacial tension.Eg;

((11)Coating the droplets)Coating the droplets:: Starch, Acacia, Gelatin,Starch, Acacia, Gelatin,Silica, Finely divided talc.Silica, Finely divided talc.

((22))Minimizing the interfacial tensionMinimizing the interfacial tension:: Mono & DiMono & Di--Glycerides, Stearates, Sorbitan monoleate.Glycerides, Stearates, Sorbitan monoleate.


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PREVENTION OF EMULSIONPREVENTION OF EMULSION

FORMATIONFORMATION

It has been obsered that once an emultionIt has been obsered that once an emultion

formed it is difficult to break the emusion.In orderformed it is difficult to break the emusion.In order

to avoid forming emulsions in the course of anto avoid forming emulsions in the course of an

extraction process:extraction process:

11)) Very cautious & gentle agitation and employingVery cautious & gentle agitation and employing

a sufficiently large liquida sufficiently large liquid--liquid interface providesliquid interface provides

a reasonably good extraction. Vigorous ora reasonably good extraction. Vigorous or

thorough shaking of the two phases is notthorough shaking of the two phases is not

required at all.required at all.


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22)) The removal of insoluable materials in a liquidThe removal of insoluable materials in a liquid

phase must be done by filtration before carryingphase must be done by filtration before carrying

out the extraction process.out the extraction process.

33)) Always prefer & use such solvent pairs that Always prefer & use such solvent pairs that

have a large density difference & high interfacialhave a large density difference & high interfacial

tension.tension.

44)) When performing extraction from water alwaysWhen performing extraction from water alwaysensure not to work at pH extremes.ensure not to work at pH extremes.

55)) In acute emulsion problems substance likeIn acute emulsion problems substance like

alumina or silica are used to resolve the problemalumina or silica are used to resolve the problem

by adsorption of emulsifying agents.by adsorption of emulsifying agents.


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PROCESS OF BREAKING OF ANPROCESS OF BREAKING OF AN

EMULSIONEMULSION

ØØ Mechanical meansMechanical means:: Coalescence may beCoalescence may be

achieved by mechanically creatingachieved by mechanically creating

turbulence on the surfaces of the droplets byturbulence on the surfaces of the droplets by

stirring with the help of a glassstirring with the help of a glass--rod.rod.

ØØ CentrifugationCentrifugation:: Where the densities of theWhere the densities of the

two liquids are appreciably differenttwo liquids are appreciably different

coalescence may be achieved bycoalescence may be achieved by

centrifugation.centrifugation.


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Ø Addition of mono & di-valent ions: Simple

emulsions are broken by adding mono-valent

salts like NaCl. Charge stabilized emulsions are

sensitive to the di-valent ions like CaCl2, MgCl2.

ØEthanol or higher alcohol: Addition of small

quantities of either ethanol or a higher alcohol aidin coalescing and emulsion.

ØSilicone-defoaming agent: A few drops of the

silicone de-foaming agent sometimes help in

breaking of an emusion.


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ØSudden cooling of emulsion: Sudden temp. drop

or freezing of an emulsion enhances the

interfacial tension between two immiscible

phases thereby causing coalescence.

Ø Altering the ratio of solvents: Coalescence may

also be achieved by altering the ratio of the

prevailing dispersed phase or by partialeveporation of the solvent.

ØThin-bed of an adsorbent: Passing of an

emulsion through a thin-bed of an adsorbent

helps in achieving coalescence.The analyte mustnot be adsorbed from either solvent.


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Prepared ByPrepared By::

Mst. Sifat LailaMst. Sifat Laila $ $ 20072007--11--7070--021021

Samina MostafaSamina Mostafa $ $

20072007--11--7070--013013Israq Binte EshaqueIsraq Binte Eshaque $ $ 20072007--11--7070--009009

Tahmina KhanomTahmina Khanom $ $ 20052005--22--7070--006006


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THANK YOUTHANK YOU

3. Liquid-Liquid Extraction.pdf

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