PHARMACEUTICAL ANALYSIS ll

LIQUID-LIQUID EXTRACTION

LIQUID-LIQUID EXTRACTION
DEFINATION

Liquid-liquid extraction is a versatile 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
SOLUTE This should be extracted

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 EXTRACT PHASE E

SOLVENT PHASE

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
The

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

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 LIQUIDLIQUID EXTRACTION

Error

due to the volume change of an extraction

Effectiveness

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: Based on the appropriate partition coefficient of an immiscible solvent pair it is possible to calculate the effectiveness of an 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-y)/ v1 Kp= y/ v2

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

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: 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

CH2Cl

3) SOLUBILITY: Two immiscible solvent become totally mixed up under a certain amount. e,g; H2O & CH2Cl2 1.6% CH2Cl2 = soluable in H2O 0.24% 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 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: 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 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 SLOWCOALESCENCE 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: Starch, Acacia, Gelatin, Silica, Finely divided talc.

(2)Minimizing the interfacial tension: Mono & DiGlycerides, 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 liquid-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 achieved by mechanically creating turbulence on the surfaces of the droplets by stirring with the help of a glass-rod. Where the densities of the two liquids are appreciably different coalescence may be achieved by centrifugation.

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

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