The Pharmaceutics and Compounding Laboratory
Extraction of Drugs

Same Aggregation State

If a compound is added to a mixture of two immiscible liquids, it will become distributed between the two layers in a definite concentration ratio. If C1 and C2 are the equilibrium concentrations of the compound in solvents 1 and 2 respectively,

then where K is the equilibrium constant or partition coefficient.

This equation applies only when the molecules in each phase are in the same state of aggregation. When association and dissociation occurs, more complex equations must be applied.

No convention exists regarding whether the concentration in the organic phase or aqueous phase should be placed in the numerator to determine K. One should always specify which way the partition coefficient is being expressed.

    e.g.

The concept of partition coefficient is applied in the pharmaceutical and health care industries in a variety of ways, including solvent extractions of drugs from dosage forms (e.g. extraction of aspirin from tablets for quality assurance tests), drugs from biological fluids (e.g. clinical laboratory analyses of drugs in blood/plasma or urine), and medicinal agents from plants (e.g. the extraction of vinca alkaloids in the development of cancer chemotherapy agents). Solvent extraction is the process of removing a constituent from one liquid phase by bringing this phase into contact with a second, immiscible, liquid phase. The number of extractions required to isolate or purify a substance is determined by the partition coefficient (K) and the relative volumes of the two phases.

At equilibrium, the weight of solute remaining in the original solvent after a single extraction (W) or after multiple extractions (Wn) is:

where,

n=# of extractions - wo = initial weight of solute - v1 = volume of the original solvent - v2 = volume of the extracting solvent

e.g. A 25 ml sample of an aqueous solution containing 0.1 g of acetanilid was extracted with three 10 ml portions of ether. The combined ether extracts were evaporated to dryness and the residue weighed. The ether/water partition coefficient for acetanilid is 3.0. What is the weight of the residue (i.e. how much is extracted)?

Wo = 0.1 g; n = 3; V1 = 25; V2 = 10

Wn = 0.0094 g (remaining in original solvent)

So, weight extracted = 0.1 g - 0.0094 g = 0.0906 g

The most efficient extraction results when a large number of extractions are carried out with small portions of extracting liquid.