Extraction techniques:
General principle and procedure involved in the solid
phase extraction and liquid-liquid extraction
LIQUID-LIQUID EXTRACTION
Introduction
Extraction is a process of removing a constituent from one phase by bringing this phase into contact with second immiscible
liquid phase.
Liquid-liquid extraction – transfer of a solute from one liquid phase to another immiscible liquid by process of partition or distribution.
Partition coefficient
Partition coefficient is dependent on temperature but not a function of absolute concentrations or the volumes of the
phases. Usually one phase is aqueous, so partition coefficient can be defined as Corg / Caqua.
Simple Extraction/Single Extraction
At equilibrium, if p is fraction of solute in upper phase and q is fraction of solute in lower phase , p is defined as
p = Amount of solute in upper phase / Total amount of solute
The ratio of volumes in upper phase and lower phase is denoted as in U = vu / vi
.
The larger the partition coefficient, the larger the percent of solute that will be found in the upper phase at equilibrium.
The ratio of
phase volume is also an equally important factor and the product KU is called capacity factor.
Multiple Extractions
• Unless K is extremely large, a significant portion of the solute will be present in both phases after a single extraction.
Therefore it is necessary to reextract with additional portions of fresh solvent (extractant) until essentially all of solute has
been removed from the phase being extracted (raffinate).
• Suppose the lower phase is raffinate and upper phase is extractant and n is the number of extractions then
Fraction of total extracted in nth extraction = Fraction of total left after (n-1)th extraction x p
• Calculation of progress of Extraction
Separation of drugs in multicomponent system
• In multicomponent system, the feasibility of resolving two substances is discussed in terms of separability factor α.
α=K1/K2
where K1 and K2 are partition coefficients of the two substances in liquid-liquid
system
• A complete separation of two solutes by simple liquid-liquid extraction requires that one of the partition coefficients be so small
(or large)
that this substance is essentially not extractable from raffinate.
• Values of apparent partition coefficients can be influenced by control of following parameters so they meet the above
requirement.
– Choice of solvents
– Control of Ionic strength
– Control of pH
– Control of ion hydrophobicity.
Effect of pH on extractability of drugs
• Most of the pharmaceutical compounds are weak acids or bases. Ionic and unionic forms of such compounds can be
interconverted merely by altering the pH of the medium.
• Control of pH is most powerful means for influencing the value of partition coefficient . A mixture of acid and base can be
readily
separated by solvent extraction.
• Solvent extraction is powerful means for the initial treatment of complex mixtures such as biological samples. Following
isolation scheme is for isolation of nonvolatile organic compounds.
– Stage One: Removal of proteins from sample.
– Stage two: separation by solvent extraction into two fractions.
Fraction A will contain acidic and neutral drug,
fraction
B all basic drugs.
– Stage three: Separation by solvent extraction of fraction A into 3 sub fractions:
• A1: the strongly acidic drugs
• A2: the weakly acidic drugs
• A3: the neutral drugs
Extraction scheme for second stage of a general
drug isolation procedure.
Fraction A contains acidic and neutral drugs;
fraction B contains basic drugs
Extraction Scheme for the subdivision of fraction A.
Continuous Extractions
Most quantitative separations by solvent extraction are performed by multiple extractions with separating funnel.
Some
extractions have been rendered more efficient and less tedious by using continuous extraction devices.