3. liquid liquid extraction

7/30/2019 3. Liquid Liquid Extraction

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PHARMACEUTICAL

ANALYSIS llLIQUID-LIQUID EXTRACTION


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LIQUID-LIQUID EXTRACTION

DEFINATION Liquid-liquid extraction is aversatile and dependable separationtechnique where in an aqueous solution is

usually brought into contact with anotherorganic solvent, exclusively immisciblewith the former, so as to affect a legitimate

and actual transfer of either one or moresolute into the latter.


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separation technique is superior

Because

Ease of use

Faster extraction timesDecreased volumes of solvent

Their superior ability to concentrate the

analytes.


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USING METARIALS

Separations may be performed by shaking thetwo liquids in a SEPARATORYFUNNEL for afew minutes, and may be extended either tolarge quantities of pharmaceutical substances ortrace levels.


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SHOWING BY FLOW CHART

Two liquids placed in separatory funnel

shaken to increase surfacearea

keep some time

two phase system


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FOR ORGANIC &INORGANICSOLUTE

In case of organic solute Two immiscibleorganic solvents (e.g; alcohol& ether) areused instead of aquous organic type of

extraction.

In case of inorganic solute one aquoussolvent & one organic solvent are

used.But if the component are watersensitive then we have to form Chelates.


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PRINCIPLES

Feed phaseFEEDPHASE CONTAININGSOLUTEThis should be extracted

ADDITION OFSOLVENTIMMICIBLE WITH FEED PHASE

SOME SOLUTES

ARE TRNSFERED FROM

FEED PHASE TO

SOLVENT PHASE

(1)FEED PHASE

(2)SOLVENT PHASE

After extraction


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AFTER EXTRACTION

THESE TWO PHASES ARE CALLED

These two phases can be separated byDISTILLATION for theirIMMISCIBILITY.

liquid-liquid extraction is also applicable

for an organic phase by adding aquous phase

FEED PHASE

RAFFINATE PHASE

OR

R

SOLVENT PHASE

EXTRACT PHASEE


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THEORY

The NearstDistribution Lawstates that at constanttemperature, a solute

distributes itselfbetween two immisiblesolvents only in aparticular ratio.

Kp = Co/CaqKp=partition coefficient

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


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LIMITATIONS

It is not thermodynamically rigorous. Thatmeans it is solely applicable to very dilutesolutions.

It does not hold good when the distributingsubstance encounters association ordistribution in either phases.


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TWO ASPECTS OF LIQUID-LIQUID EXTRACTION

Error due to the volume change

Effectiveness of an extraction


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1. Error due to the volume change: if twoimmiscible solvent is under extraction

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

To avoid error of volume change, the

Procedure we adopted is:

Measure the volume of the phase employedfor the analysis and incorporate this volume inthe calculations.


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Separate the phase quantitatively andsubsequently dilute to known volume.

Separate the phase quantitatively and make useof the entire volume in the remaining steps of theanalysis.

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


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INDUSTRIALY EXTRACTION


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2.Effectiveness of an extraction: Based on theappropriate partition coefficient of an immisciblesolvent pair it is possible to calculate theeffectiveness of an extraction.Let,

x moles of solute in v2volume when solvent is a

(x-y) moles solute in v1 volume when solvent is b(x-y)/ v1

Kp=y/ v2


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or, Kp =(x/ v1-x/ v1) v2/y

or, Kp =x/y.v2/v1-v2/v1or, Kp =v2/v1(x/y-1)

or, Kp. v2/v1=(x/y-1)

or, x/y= (v2/v1. Kp + 1)

or, y/x= (v1/v2. Kp + 1)

After the total extraction,(v1/v2. Kp + 1)

fn =

n


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Here,

Kp = partition coefficient

fn = fraction of extracted


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SOLVENT SELECTION CRITERIA

1) MISCIBILITY: Solvents defined as if theTwo components can be mixed together in

all proportions without forming two separate

phases.

Solvent miscible with water in allproportions includeAcetone, Acetonitrile,

Dimethyl acetamide, N,N-dimethylformamide,

Dimethyl sulfoxide, 1,4,-dioxane etc.


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2) DENSITY: If density difference is high thenimmiscibility will be high. On other hand if density

difference is low it causes miscibility.

e.g; H2O & CH2Cl

here the density of CH2Cl is high.& H2O is low.

So, CH2Cl will come down to the

lower Portion of the separatoryFunnel & H2O will come up.

H2O

CH2Cl

) SO


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3) SOLUBILITY: Two immiscible solvent

become totally mixed up under a certain amount.

e,g; H2O & CH2Cl21.6% CH2Cl2 = soluable in H2O

0.24% H2O = soluable in CH2Cl2

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

complex.


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FACTORS INFLUENCE SOLVENT

EXTRACTION

Effect of temparature: Temparature mustbe fixed through the process because itdepends on the solubility of the substance

in two respective solvevts.

Kp = S1/S2

Solubility of solute in solvent a

Solubility of solute in solvent b

Eff t f H t ti It b


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Effect of pH on extraction: It may be

observed that the pH for an extraction system

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

the extractable form, that obviously suggests

that the analyte should always be in the form ofeither a free base or a free acid.


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EMULSION

EMULSION: Emulsion may be defined as adispersed system containing at least two I

mmiscible liquid phases.

The effectiveness and meaningful extractionof a solute is rended almost impossible

when there is an emulsion formation during

an extraction process. Emulsion formationmakes the separation of the two phases

difficult.


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FACTORS CAUSES SLOW-

COALESCENCE 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.

2 U ll f t t d th i t f i l


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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 formationOf a net charge on the droplets. Because all

droplets shall essentially bear the similar charge,

naturally they will repel one another therebypreventing coalescence.

I f t th t l d th ti


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In fact,there are many natural and syntheticsubstances that are profusely incorporated in theformulation of drugs which are found to stabilize

emulsions either by coating the droplets or byminimizing the interfacial tension.Eg;

(1)Coating the droplets: Starch, Acacia, Gelatin,

Silica, Finely divided talc.

(2)Minimizing the interfacial tension: Mono & Di-

Glycerides, Stearates, Sorbitan monoleate.


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PREVENTION OF EMULSIONFORMATION

It has been obsered that once an emultion

formed it is difficult to break the emusion.In order

to avoid forming emulsions in the course of anextraction process:

1) Very cautious & gentle agitation and employing

a sufficiently large liquid-liquid interface providesa reasonably good extraction. Vigorous or

thorough shaking of the two phases is not

required at all.

2) Th l f i l bl t i l i li id


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2) The removal of insoluable materials in a liquidphase must be done by filtration before carryingout the extraction process.

3) Always prefer & use such solvent pairs thathave a large density difference & high interfacialtension.

4) When performing extraction from water alwaysensure not to work at pH extremes.

5) In acute emulsion problems substance like

alumina or silica are used to resolve the problemby adsorption of emulsifying agents.


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PROCESS OF BREAKING OF ANEMULSION

Mechanical means: Coalescence may beachieved by mechanically creatingturbulence on the surfaces of the droplets by

stirring with the help of a glass-rod.

Centrifugation: Where the densities of the

two liquids are appreciably differentcoalescence may be achieved bycentrifugation.

Addition of mono & di valent ions: Simple


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Addition of mono & di-valent ions: Simpleemulsions are broken by adding mono-valentsalts like NaCl. Charge stabilized emulsions are

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

Ethanol or higher alcohol: Addition of small

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

Silicone-defoaming agent: A few drops of thesilicone de-foaming agent sometimes help inbreaking of an emusion.

Sudden cooling of emulsion: Sudden temp drop


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Sudden cooling of emulsion: Sudden temp. dropor freezing of an emulsion enhances theinterfacial tension between two immiscible

phases thereby causing coalescence.Altering the ratio of solvents: Coalescence mayalso be achieved by altering the ratio of the

prevailing dispersed phase or by partialeveporation of the solvent.

Thin-bed of an adsorbent: Passing of an

emulsion through a thin-bed of an adsorbenthelps in achieving coalescence.The analyte mustnot be adsorbed from either solvent.


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Prepared By:

Mst. Sifat Laila 2007-1-70-021

Samina Mostafa 2007-1-70-013Israq Binte Eshaque 2007-1-70-009

Tahmina Khanom 2005-2-70-006


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3. liquid liquid extraction

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