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Distribution
Coefficient

Distribution coefficient
(partition coefficient)

Generally, partitioning
is the movement of drug
molecules from one
phase (aqueous) to
another phase (organic)
and vice versa.

Distribution of a solute
between two immiscible
solvents

When two immiscible solvents are in

contact, a dissolved solute will distribute
itself between the two according to a
predetermined equilibrium
K=

K: is distributional coefficient, it is the ratio

of concentration of substance in organic
and aqueous phase at equilibrium.

In some cases, substance has different molecular weight in

the two immiscible solvents for example:
when drug is associated to form a polymer of n units in organic
phase and monomers in aqueous phase
An (organic phase)

nA (aqueous phase)

Partition coefficient is the ratio between the concentrations of

solute in solvent one to the concentration of solute in solvent two
provided that:
1) Solvent one and solvent two are immiscible.
2) The solute concentration in each solvent is below saturation
concentration.
3) Equilibrium is attained.

Applications

Extraction of natural substances.

In fatty base suppositories, the release of the drug depends on
the form of drug and its distribution coefficient. So, drugs,
have high k values, favor the oily phase leading to slow
release of the drug.
Biotransformation where drug metabolites are less lipid
soluble than the parent drug i.e. more polar allowing its urine
excretion. e.g. Aromatic ring hydroxylation of salicylic acid
(more lipid) to gentisic acid (more polar).

Extraction

conc. (organic phase)

Kc = partition coefficient =
conc. (aqueous phase)

K =

(Distribution law)

X0: gm of the substance

V2: volume of original solution
X1/V1: concentration in the extracting solution
(X0 X1)/V2: concentration in original solution
N.B: extraction by several portions of the extracting solvent is more complete than when the same
volume is used once.

example: Given compound A, K (ether:water) = 4.0, how

much of A can be extracted from a solution of 10.0 g of A
in 100 mL of water with a single portion of 100 mL of
ether?

X / 100 mL ether
Kc = 4.0 = --------------(10.0 X) / 100 mL water
X = 8.0 grams of A extracted into the ether

same as above, but extract two times with 50 mL of ether each time.

X / 50 mL ether
first extraction: Kc = 4.0 =

------(10.0 X) / 100 mL water

X = 6.67 grams of A extracted

Y / 50 mL ether
second extraction: Kc = 4.0 = ----------(3.33 Y) / 100 mL water
Y = 2.22 grams of A extracted

total extracted = X + Y = 6.67 + 2.22 = 8.89 gra ms

Problems
1)How many grams of an organic substance are
extracted with 100 ml of ether from 100 ml of 1%
aqueous when these 100 ml of ether were added:
a) at once (100 ml)
b) on 2 portions (50 ml, 50 ml)
N.B. K between ether and water = 20

2) If 100 ml of a 5% aqueous solution of salicylic

acid was extracted with 4 portions 25 ml each of
chloroform, how much more will be removed
from the aqueous phase than by a single
extraction with 100 ml of chloroform. (K
between chloroform and water = 2.3)

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Determination of partition
coefficient of benzoic acid
between chloroform /
water system.

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Procedure

1) Dissolve 0.5 g benzoic acid in 5 ml chloroform (as solubility of benzoic acid in chloroform is greater
than its solubility in water) in test tube.
2) Add 5 ml water to the test tube.
3) Transfer to a separating funnel.
4) Shake well for 15 min and periodically relive the pressure inside the funnel through opening its
stopper.
5) Leave it for 10 min till complete separation of two layers (upper layer is aqueous and the lower layer
is organic chloroform layer).
6) Open the lower tap carefully and discard the organic chloroform layer in test tube.
7) Take 3 ml of the remaining aqueous layer and transfer to a flask.
8) Add dope of ph.ph indicator.
9) Titrate it with 0.1 NaOH till the color change from colorless to pink.
10)Record the end point in ml.
11)Calculate K = C org / C aq

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Separating Funnel

CCl4 and CHCl3 are the only two organic

solvents denser than water.

Calculation of k of Benzoic acid

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between chloroform / water
E.P=ml
system
C initial =(.5 g)/(5 ml)=0.1 g/ml
C aq=(E.Pequilvalence)/(volume taken)= g/ml
Equivalnce =(equivalent weight(of analyte)normality of
titrant)/1000=g/ml
Equivalent weight=(molecular weight (122))/(no of replaceable
hydrogen or hydroxyl group )=g/mol
C org=C ini C aq=g/ml
K=C org/C aq =

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Any Questions ?