PHARMACEUTICAL

ANALYSIS ll
LIQUID-LIQUID EXTRACTION

LIQUID-LIQUID EXTRACTION
DEFINATION

Liquid-liquid extraction is a
Liquidversatile and dependable separation
technique where in an aqueous solution is
usually brought into contact with another
organic solvent, exclusively immiscible
with the former, so as to affect a legitimate
and actual transfer of either one or more
solute into the latter.

separation technique is superior

Because
Ease of use
Faster extraction times
Decreased volumes of solvent
Their superior ability to concentrate the
analytes.

USING METARIALS

Separations may be performed by shaking the

two liquids in a SEPARATORY FUNNEL for a
few minutes, and may be extended either to
large quantities of pharmaceutical substances or
trace levels.

SHOWING BY FLOW CHART

Two liquids

placed in separatory funnel

shaken to increase surface

area

keep some time

two phase system

FOR ORGANIC &INORGANIC SOLUTE

In 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 solute one aquous
solvent & one organic solvent are
used.But if the component are water
sensitive then we have to form Chelates.

PRINCIPLES
Feed
phase
FEED PHASE
CONTAINING

This should be extracted

SOLUTE

IMMICIBLE WITH FEED PHASE

ADDITION OF SOLVENT

SOME SOLUTES
ARE TRNSFERED FROM
FEED PHASE TO
SOLVENT PHASE

(1)FEED PHASE
After extraction
(2)SOLVENT PHASE

AFTER EXTRACTION
THESE TWO PHASES ARE CALLED
FEED PHASE

RAFFINATE PHASE
OR
R

SOLVENT PHASE

EXTRACT PHASE
E

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

THEORY
Nearst
Distribution Law
states that at constant
temperature, a solute
distributes itself
between two immisible
solvents only in a
particular ratio.
Kp = Co/Caq

The

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

LIMITATIONS
It

is not thermodynamically rigorous. That

means it is solely applicable to very dilute
solutions.
It does not hold good when the distributing
substance encounters association or
distribution in either phases.

TWO ASPECTS OF LIQUIDLIQUIDLIQUID EXTRACTION

Error

due to the volume change

Effectiveness

of an extraction

1.

Error due to the volume change: if two

immiscible solvent is under extraction
process, then the volume of the two individual
phases will be different comparison to the
initial volumes.

To avoid error of volume change, the

Procedure we adopted is:
Measure the volume of the phase employed
for the analysis and incorporate this volume in
the calculations.

Separate

the phase quantitatively and

subsequently dilute to known volume.
Separate the phase quantitatively and make use
of the entire volume in the remaining steps of the
analysis.
Carry a maker substance through the extraction
to automatically compensate for volume changes.

INDUSTRIALY EXTRACTION

2. Effectiveness of an extraction:
extraction: Based on the
appropriate partition coefficient of an immiscible
solvent pair it is possible to calculate the
effectiveness of an extraction.
extraction.
Let,
x moles of solute in v2 volume when solvent is a
(x--y) moles solute in v1 volume when solvent is b
(x
(x--y)/ v1
(x
Kp=
y/ v2

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

Here,
Kp = partition coefficient
fn = fraction of extracted

SOLVENT SELECTION CRITERIA

1) MISCIBILITY: Solvents defined as if the
Two components can be mixed together in
all proportions without forming two separate
phases.
Solvent miscible with water in all
proportions include Acetone, Acetonitrile,
Dimethyl acetamide, N,N-dimethylformamide,
Dimethyl sulfoxide, 1,4,-dioxane etc.

2) DENSITY
DENSITY:: If density difference is high then
immiscibility 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 separatory
Funnel & H2O will come up.

H2O

CH2
CH
2Cl

3) SOLUBILITY
SOLUBILITY:: Two immiscible solvent
become totally mixed up under a certain amount.
e,g; H2O & CH2Cl2
1.6% CH2Cl2 = soluable in H2O
0.24
24%
% H2O = soluable in CH2Cl2
To overcome this problem we can use which
solubility is zero.Otherwise it would be more
complex.

FACTORS INFLUENCE SOLVENT

EXTRACTION
Effect

of temparature:
temparature: Temparature must
be fixed through the process because it
depends 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

Effect of pH on extraction:
extraction: It may be
observed that the pH for an extraction system
must be selected in such a fashion so that the
maximum quantity of the analyte is present in
the extractable form, that obviously suggests
that the analyte should always be in the form of
either a free base or a free acid.

EMULSION
EMULSION: Emulsion may be defined as a
EMULSION:
dispersed system containing at least two I
mmiscible liquid phases.
The effectiveness and meaningful extraction
of a solute is rended almost impossible
when there is an emulsion formation during
an extraction process. Emulsion formation
makes the separation of the two phases
difficult.

FACTORS CAUSES SLOWSLOWCOALESCENCE EMULSION

The breaking of an emulsion could be a slow
process. There are a number of factors
which may be responsible for the slowcoalescence 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. 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.

In fact,there are many natural and synthetic

substances that are profusely incorporated in the
formulation of drugs which are found to stabilize
emulsions either by coating the droplets or by
minimizing the interfacial tension.Eg;
(1)Coating the droplets
droplets:: Starch, Acacia, Gelatin,
Silica, Finely divided talc.
(2)Minimizing the interfacial tension:
tension: Mono & DiDiGlycerides, Stearates, Sorbitan monoleate.

PREVENTION OF EMULSION
FORMATION
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 an
extraction process:
1) Very cautious & gentle agitation and employing
a sufficiently large liquidliquid-liquid interface provides
a reasonably good extraction. Vigorous or
thorough shaking of the two phases is not
required at all.

2) The removal of insoluable materials in a liquid

phase must be done by filtration before carrying
out the extraction process.
3) Always prefer & use such solvent pairs that
have a large density difference & high interfacial
tension.
4) When performing extraction from water always
ensure not to work at pH extremes.
5) In acute emulsion problems substance like
alumina or silica are used to resolve the problem
by adsorption of emulsifying agents.

PROCESS OF BREAKING OF AN
EMULSION
Mechanical

means:: Coalescence may be

means
achieved by mechanically creating
turbulence on the surfaces of the droplets by
stirring with the help of a glassglass-rod.

Centrifugation
Centrifugation::

Where the densities of the

two liquids are appreciably different
coalescence may be achieved by
centrifugation.

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.
Ethanol

or higher alcohol: Addition of small

quantities of either ethanol or a higher alcohol aid
in coalescing and emulsion.
Silicone-defoaming

agent: A few drops of the

silicone de-foaming agent sometimes help in
breaking of an emusion.

Sudden

cooling of emulsion: Sudden temp. drop

or freezing of an emulsion enhances the
interfacial tension between two immiscible
phases thereby causing coalescence.
Altering the ratio of solvents: Coalescence may
also be achieved by altering the ratio of the
prevailing dispersed phase or by partial
eveporation of the solvent.
Thin-bed of an adsorbent: Passing of an
emulsion through a thin-bed of an adsorbent
helps in achieving coalescence.The analyte must
not be adsorbed from either solvent.

Prepared By:
By:
Mst. Sifat Laila 2007
2007--1-70
70--021
Samina Mostafa 2007
2007--1-70
70--013
Israq Binte Eshaque 2007
2007--1-70
70--009
Tahmina Khanom 2005
2005--2-70
70--006

THANK YOU