Chemistry Reference
In-Depth Information
2
Partition coefficient and biopharmacy
When a substance (or
solute
) is added to a pair of immiscible solvents, it
distributes itself between the two solvents according to its affinity for each
phase. A polar compound (e.g. a sugar, amino acid or ionised drug) will
tend to favour the aqueous or polar phase, whereas a non-polar compound
(e.g. an unionised drug) will favour the non-aqueous or organic phase. The
added substance distributes itself between the two immiscible solvents
according to the partition law, which states that 'a given substance, at a
given temperature, will partition itself between two immiscible solvents in
a constant ratio of concentrations'. This constant ratio is called the
partition
coefficient
of the substance, and may be expressed mathematically as
[organic]
P
——----
[aqueous]
(2.1)
where
P
is the partition coefficient of the substance; [organic] is the concen-
tration of substance in the organic, or oil phase; and [aqueous] is the
concentration of substance in the water phase.
As an example, consider the distribution of 100 mg of a drug between
50 mL of an organic solvent (e.g. ether, chloroform or octanol) and 50 mL
of water. The drug is added to the two immiscible solvents in a separating
funnel and allowed to equilibrate. When the organic layer is analysed, it is
found to contain 66.7 mg of compound. From these data the partition coef-
ficient and the percentage of the drug extracted into the organic layer can
be calculated (see Figure 2.1).
The mass of drug in the water phase
100
66.7 mg
33.3 mg; the
concentration of drug in the organic phase
66.7/50
1.33 mg mL
1
, and
the concentration of drug in the water phase
33.3/50
0.67 mg mL
1
.
Therefore, the partition coefficient is given by
1.33 mg mL
1
[organic]
——----
———------
2
0.67 mg mL
1
[aqueous]
The partition coefficient is a ratio of concentrations, so the units cancel and
P
has no units.
