Partition coefficient, often denoted as P or P_oct, is a measure of how a solute distributes between two immiscible (unmixable) solvents. It is commonly used in chemistry, biochemistry, and pharmacology to understand the distribution of a compound between different phases, such as between a hydrophobic organic solvent and water. In experimental settings, the partition coefficient is determined by measuring the concentrations of the solute in each phase. The values obtained provide insights into the solute's behavior and can guide decisions in various scientific and industrial processes.

1. Pal’s & Pandey
M. Pharm (Pharmaceutics)
Pharmaceutics Practical: “Partition Coefficient”
*Rahul Pal, Prachi Pandey
M. Pharm (Pharmaceutics)
*Department of Pharmaceutics, Nims Institute of Pharmacy, Nims University Rajasthan, Jaipur,
3030121, India.
AIM/OBJECT
To determine the partition co-efficient of known Benzoic acid between Benzene and water
OR
To determine partition coefficient of unknown drug molecule sample
REQUIREMENT
 Chemical: Saturated solution of benzoic acid in benzene, Benzene, 0.01N NaOH, O.1N NaOH,
Distilled water and Unknown drug sample.
 Glassware’s/Apparatus: Separating funnel (250 ml), conical flask, pipette, burette, stoppered bottles
etc.
INTRODUCTION/BACKGROUND
The movement of molecules from one phase to another phase is called partitioning. The distribution or
partition of a solute between immiscible liquid is known as Nernst’s Distribution Law or simply
distribution law or partition law. Partition coefficients is the measurement of lipophilicity and
hydrophilicity of any unknown sample.
Definition: The partition coefficients is defined as “The ration of unionized drug distributed between
organic phase and aqueous phase at equilibrium”.
OR
“Partition (P) or Distribution Coefficient (D) is the ratio of concentration of a compound in the two phases
of a mixture of two immiscible solvents at equilibrium”.
Pal’s & Pandey
LAB’S

2. Pal’s & Pandey
M. Pharm (Pharmaceutics)
Pharmaceutics Practical: “Partition Coefficient”
Partition Coefficient (P) = X0 / Xw
Where; X0 = Fraction of drug in organic phase, Xw = Fraction of drug in aqueous phase.
Equilibrium Constant, K = Co/ Cw
The constant is call coefficient (K) or the distribution coefficient of the solute between the two solvents.
Where; K = Partition coefficients/Distribution coefficient/Distribution ratio, Co= Equilibrium conc. of
substance in organic phase and Cw= Equilibrium con. of substance in aqueous phase.
General Feature:
 Partition coefficients have no units.
 If the partition coefficients of drug is more than one it is more lipophilic.
 If the partition coefficients of drug is less than one it is hydrophilic (less lipophilic).
MEASUREMENT OF PARTITION COEFFICIENT: It can be measured by using the followings
methods:
 *Shake flask (or tube) method.
 *HPLC method.
 Electrochemical method.
 Slow-stirring method.
 Estimation method based on individual solubilities.
PROCEDURE: The procedure as follows:
To prepare the following mixtures in separating funnels:
Set I: 25ml water + 25 ml of saturated solution of benzoic acid in benzene
Set II: 25 ml water + 20 ml saturated solution of benzoic acid in benzene + 5 ml benzene
Set III: 25ml water + 15 ml saturated solution of benzoic acid in benzene + 10 ml benzene
Shake the mixture in the separating funnel vigorously for about 30 minutes so that the benzoic acid gets
distilled the two solvents and the distribution equilibrium is reached. Allow the flasks to stand for 10
minutes to separate layers (remove the stopper of the separating funnel and keep its mouth open during
this period to facilitate. Drain off the lower aqueous layers in 3 different stoppered dry bottles. (Discard

3. Pal’s & Pandey
M. Pharm (Pharmaceutics)
Pharmaceutics Practical: “Partition Coefficient”
the intermediate layer phases. Benzene layer remains in the separating funnels. Using a dry pipette take 5
ml of organic layer of conical flask containing 10ml of water and titrate against 0.1 N NaOH using
phenolphthalein as an indicate colorless to pink. Pipette out 10 ml of the aqueous layer using a dry pipette
and titrate it against 0.01 N NaOH, phenolphthalein as an indicator. End point will be colorless to pink.
OBSERVATIONS
Ex. No. Vorg. Vaq. Norg.= Corg. Naq. = C aq. K Log Corg. Log Caq.
I
II
III
Mean Partition coefficient K =
Where, Vorg = Volume in ml of 0.1N Sodium hydroxide per 5ml of organic layer, Vaq = Volume in ml of
0.01N Sodium hydroxide per 10ml of aqueous layer, Norg = Normality of organic layer, Naq = Normality
of aqueous layer, Corg = Concentration of organic layer in g mole/lit = Normality (N ), Caq = Concentration
of aqueous layer in g mole/lit = Normality (N ) and K= Caq /Corg
1/2
= Partition coefficient of benzoic acid
in water and benzene.
CALCULATIONS
Set I
1. For Organic layer
Normality of Sodium hydroxide (N1 = 0.1N), Volume of organic layer pipetted (V2) = 5ml
N1 V1 (Sodium hydroxide) = N2 V2 (Organic layer)
N2 =
𝟎.𝟏 𝒙 𝑽𝟏
𝟓
= Norg
Similarly calculate concentration of benzoic acid in organic layer of set II and III.
2. For aqueous layer
Normality of Sodium hydroxide (N1 = 0.01N), Volume of organic layer pipetted (V2) = 10 ml
N1 V1 (Sodium hydroxide) = N2 V2 (Aqueous layer)
N2 =
𝟎.𝟏 𝒙 𝑽𝟏
𝟏𝟎
= Norg
Similarly calculate concentration of benzoic acid in aqueous layer of set II and III.

4. Pal’s & Pandey
M. Pharm (Pharmaceutics)
Pharmaceutics Practical: “Partition Coefficient”
Graph:
Plot the graph of log Caq Vs log Corg
Partition Coefficients K =
𝐂𝐚𝐪.
𝐂𝐨𝐫𝐠𝟏/𝐧
Log Caq. =
𝟏
𝒏
log Corg + log K
Above equation, is equation of a straight line (i.e. y = mx+c)
RESULTS FROM THE GRAPH
Slop (m) = 1/n =
Therefore n is closes to =
Substituting the value of slope line in the equations
Log Caq. = log Corg + log K = log Corg + log K
Therefore, Log K =…………..
K = …………….
SHAKE FLASK METHOD (SEPARATION METHOD): The procedure as follows:
 In this method we take a separating funnel, in which we fill 50ml oil and 50 ml of water.
 Now transfer the sample drug into the funnel and dissolve drug by shaking process.
 When drug is dissolved completely, open the stopper which is below and separate both of the solvents
in different flask.
 Now partition coefficient can determine the conc. of dissolved drug in both of the solvents by various
laboratory method (UV-Spectroscopy).

5. Pal’s & Pandey
M. Pharm (Pharmaceutics)
Pharmaceutics Practical: “Partition Coefficient”
CONCLUSION:
1. Partition co-efficient of benzoic acid between distilled water and benzene is ____________ by
calculation____________ by graph.
2. Since Caq /Corg is practically constant benzoic acid exists as a dimer (n=2) in benzene.
3. Molecular condition of benzoic acid in benzene is 1/slope = n = ____ , molecules of benzoic acid
associassion.
REFERENCES:
01. More HN, Hajare AA. Practical physical pharmacy, career publications, 2010: 73-76.
02. Pal, Rahul & Pandey, Prachi. (2023). A Text Book of "Pharmaceutics Practical-1" M. Pharm
(Pharmaceutics) Ist Sem..
03. Pandey, Prachi & Pal, Rahul & Thakur, Shiva Kant. (2023). "A Text Book of Pharmaceutics-1" B.
Pharm 1st sem. (Ist Year).
04. Pal, Rahul & Pandey, Prachi. (2023). DETERMINATION OF PKPD OF DRUG USING
WINNONLIN SOFTWARE: "PHARMACEUTICS PRACTICAL-II".
10.13140/RG.2.2.26483.30244.
05. Pal, Rahul & Pandey, Prachi & Saxena, Archita & Koli, Manju & Thakur, Shiva Kant. (2023). A
TEXT BOOK OF PHARMACEUTICS (Diploma in Pharmacy) D. Pharma, Ist Year.