Physical pharmacy Dr. Khaled Sh.

Shamareekh
Lectures (9)

Partitioning (log P)
When a solute is added to a mixture of two immiscible solvents, it will dissolve in different
amount for the two solvents, and the solute concentrations in the two solvents will be at
equilibrium.

 The movement of drug molecules from one liquid phase to another liquid phase is called
partitioning.

The extent of partition of solute is determined by the ratio of the concentrations between the
two solvents and it will be constant, which is given by:

Where: P is the partition coefficient of solute between the two solvents

C1 and C2 are the concentrations of solute in first solvent and second solvent,
respectively.

 The most important of this coefficient is the partition coefficient of drugs between the
water (aqueous phase) and organic phases. This property has important applications in
pharmaceutical field.

 To determine this property (partition coefficient), a simple mixture solvent model is

commonly used, which is composed of water and 1-octanol.

 It is found that 1-octanol give better correlation between the calculated partition coefficient
and the biological activity than other organic solvents.

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Physical pharmacy Dr. Khaled Sh. Shamareekh
Lectures (9)

The partition coefficient for the partitioning of a solute between water (w) and 1-octanol (o)
can be written as:

Where: P is the partition coefficient of solute between the organic and aqueous solvents
Co is the concentration of solute in the organic solvent
Cw is the concentration of solute in aqueous solvent

When a drug is lipophilic (i.e. it has a high affinity for the octanol phase) the value of P will be
greater than 1, and when the drug is hydrophilic the value of P will be less than 1.

Because hydrophilic drugs will give very small P values, log P values are often used, in which the
hydrophilic drugs will have a negative value and lipophilic drugs a positive value.

For lipophilic drugs, P > 1 or log P is positive.

For hydrophilic drugs, P < 1 or log P is negative.

The log P values describe the degree of hydrophilicity and lipophilicity of drugs and provide
useful information regarding their distribution in the body.

The lipophilic drugs will generally accumulate in fat tissues and intracellularly.

The hydrophilic drugs will remain in the plasma or blood and will be rapidly excreted.

Example:

If the compound has a log P = 5, then the compound is 100,000 times more soluble in the
partitioning solvent. A log P = –2 means that the compound is 100 times more soluble in water,
i.e., it is quite hydrophilic.

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Physical pharmacy Dr. Khaled Sh. Shamareekh
Lectures (9)

Where: P = Co/Cw = 100000/1 log P = 5

P = Co/Cw = 1/100 log P = log (1/100) = log

1 – log 100 = 0 – 2 = – 2 log P – 2

Determination of log P

Log P values can be determined experimentally

Shake-flask method

The shake-flask method is a quick, simple and

near universally applicable way of determining
the partition coefficient.

1. The drug is dissolved in the aqueous phase to a known concentration.

2. Equal volumes of aqueous drug solution and n-octanol are then mixed in a separating
funnel.
3. The mixture is shaken vigorously for about 30 min.
4. The phases are allowed to separate (5 min).
5. Then the concentration of the drug remaining in the aqueous phase is determined by
the adequate analytical method.

Applications of log P

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Physical pharmacy Dr. Khaled Sh. Shamareekh
Lectures (9)