The document discusses the partition coefficient (log P), which measures the solubility of un-ionized solutes between aqueous and hydrophobic solvents, and its relevance in drug distribution within the body. It summarizes methods for measuring the partition coefficient, its limitations, and applications in predicting drug solubility, absorption, and release from pharmaceutical formulations. Additionally, it provides examples of various drugs categorized by their strength as acids or bases related to their absorption characteristics.

1. Physical Pharmacy Lecture Series
Lecture# 08
Physico-chemical Principles (Solution)
By: Pharmacist Tayyeb Official

2. PARTITION COEFFICIENT
• Partition Coefficient
• Measurement of partition
coefficient
• General feature of partition
coefficient
• Limitation of partition coefficient
• Application of partition coefficient
• Solubility Vs partition coefficient

3. PARTITION COEFFICIENT (Log P or Log K) :
The partition coefficient, abbreviated P or K, is defined as :
• “a particular ratio of the
concentrations of a solute between the
two solvents (a biphasic of liquid
phases), specifically for un-ionized
solutes,” and
• “the logarithm of the ratio (partition
coefficient) is called log P.”
• It is useful in estimating the distribution of drugs within the
body.
• Partition coefficients have no units.
PARTITION COEFFICIENT

4. Explanation:
• measure of the difference in solubility.
• one solvents is aqueous while the
second is hydrophobic such as 1-
octanol or olive oil.
• Octanol and olive oil (are believed to
represent the lipophilic characteristics
of biological membrane better than
other organic solvents such as
chloroform.)
• The n-octanol/water partitioning system
(mimic the lipid membranes/water
systems found in the body.)
PARTITION COEFFICIENT

5. • If solute preferably
distribute in octanol then
• P > 1 and log P > 0.
• If solute preferably
distribute in water then
• P < 1 and log P < 0.
PARTITION COEFFICIENT

6. General Features (PARTITION COEFFICIENT):
• Drugs partition themselves between the aqueous phase
and lipophilic membrane.
• If the partition coefficient of drug is more than one it is
more lipophilic
• If the partition coefficient of drug is less than one it is
less lipophilic.
• It is a measure of how well substance partitions between
lipid and water.
• Hydrophobic drugs with high partition coefficients are
preferentially distributed to hydrophobic compartments
such as bi-lipid layers of cells.
• Hydrophilic drugs with low partition coefficient are
found in hydrophilic compartments such as blood serum.
• Partition coefficients have no units.
PARTITION COEFFICIENT

7. MEASUREMENT OF
PARTITION COEFFICIENT:
It can be measured by using following methods.
• Shake flask (or tube) method.
• Separating Funnel
• HPLC method.
• Electrochemical method.
• Slow-Stirring Method.
• pH metric method
PARTITION COEFFICIENT

8. Limitations:(PARTITION COEFFICIENT):
1) Dilute solutions:
The concentration of solute must be low in two solvents. This
law does not holds good when the concentrations are high.
2) Constant temperature:
Temperature should be kept constant throughout the
experiment, since solubility is dependent on temperature.
3) Same molecular state:
Solute must be in the same molecular state in both the solvent.
This law does not hold, if there is association or dissociation of solute
molecules in one of the solvents.
4) Equilibrium concentration:
This is achieved by shaking the mixture for longer time.
5) Non-miscibility of solvents:
So, the solvents are to be allowed for separation for a sufficient
time.
PARTITION COEFFICIENT

9. Applications of PARTITION COEFFICIENT:
1) Solubility:
Solubility of drugs in water and other
solvents and in mixture of solvents can be
predicted.
2) Drug absorption:
Drug absorption in vivo can be predicted.
3) Character of drug molecules:
The oil-water partition coefficients are
indicative of lipophilic hydrophilic character of
drug molecules.
PARTITION COEFFICIENT

10. Applications of PARTITION COEFFICIENT:
4) SAR:
Structure activity relationship (SAR) for a series of
drugs can be studied.
5) Extraction:
Drugs from biological fluids such as blood, tissue and
urine can be extracted efficiently by the principle of Multiple
Extraction.
6) Emulsions:
Effective concentration of preservative can be
established for the storage of emulsion and other dosage forms.
7) Release of drug:
Release of drugs from ointments and creams can be
predicted.
PARTITION COEFFICIENT

11. Applications of PARTITION COEFFICIENT:
8) Chromatography:
Partition principle is used in partition chromatography
to separate organic substance from mixtures.
9) Complexation:
Certain complexes partition difficulty to the substrate
and complexing agent. This change in lipophilicity will affect the
activity of the drug and can also be used to measure the extent of
Complexation.
10) Chemical modification:
Chemical changes related to lipid solubility and its
effect on GI absorption are best exemplified by barbiturates.
PARTITION COEFFICIENT

12. Comparison
PARTITION COEFFICIENT

13. Drugs pKa pH/site of absorption
Very weak acids (pKa > 8.0)
Phenobarbital 8.1 Unionised at all pH
values; absorbed along
the entire length of GIT.
Hexobarbital 8.2
Phenytoin 8.2
Moderately weak acids (pKa 2.5 to 7.5)
Cloxacillin 2.7 Unionised in gastric pH
and ionised in intestinal
pH; better absorbed
from the stomach.
Aspirin 3.5
Ibuprofen 4.4
Stronger acids (pKa < 2.5)
Disodium cromoglycate 2.0 Ionised at all pH values;
poorly absorbed from
GIT.
PARTITION COEFFICIENT

14. Drugs pKa pH/site of absorption
Very weak bases (pKa< 5.0)
Theophylline 0.7 Unionised at all pH
values; absorbed along
the entire length of GIT.
Caffeine 0.8
Diazepam 1.7
Moderately weak bases (pKa 5 to 11.0)
Reserpine 6.6 Ionised at gastric pH,
relatively unionised at
intestinal pH; better
absorbed from
intestine.
Codeine 8.2
Amitriptyline 9.4
Stronger bases (pKa > 11)
Mecamylamine 11.2 Ionised at all pH values;
poorly absorbed from
GIT.
Guanethidine 11.7
PARTITION COEFFICIENT

15. Difference
s

16. Physical Pharmacy
Other topic of solution:
Lecture# 08 Done
Lecture# 07 Prev.
Lecture# 06 Prev.

17. End
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