PARTITION COEFFICIENT

1. DETERMINATION OF
PARTITION COEFFICIENT
OF A DRUG MOLECULE
AND
ITS APPLICATION IN
PREFORMULATION
STUDIES
MOUMITA BANERJEE
24201911013
B.PHARMA 4TH YEAR
UNDER GUIDANCE OF:-
MR. P.K.DUTTA

2. WHAT IS PARTITION COEFFICIENT
In the Chemical and Pharmaceutical Sciences a partition coefficient is
the ratio of concentrations of a compound in the two phases of a
mixture of two immiscible liquids at equilibrium.
The partition coefficient is a ratio of concentrations of un-ionized
compound between the two liquid phases. The logarithm of the ratio of
the concentrations of the un-ionized solute in the solvents is called log
P: When one of the solvents is water and the other is a non-polar
solvent, then the log P value is also known as a measure of lipophilicity.
For example, in an octanol-water system:

3. WHY IS IT REQUIRED TO DETERMINE IN PREFORMULATION
STUDIES
• It describes the process of optimizing the delivery of drug thorough
determination of physical, chemical properties of new drug molecule
that affect drug performance and development of an efficacious
stable and safe dosage form.
• Preformulation studies on a new drug molecule provide useful
information for subsequent formulation of a physicochemically stable
and bio-pharmaceutically suitable dosage form

4. METHODS OF DETERMINATION OF PARTITION COEFFICIENT
OF A DRUG MOLECULE
Shake flask (or
tube) method
HPLC
determination
Electrochemical
methods

5. APPLICATIONS
1. Pharmacology - A drug's distribution coefficient strongly affects how easily the drug can reach its intended target in the
body, how strong an effect it will have once it reaches its target, and how long it will remain in the body in an active form.
2. Pharmacokinetics - In the context of pharmacokinetics (what the body does to a drug), the distribution coefficient has a
strong influence on ADME properties of the drug.
3. Pharmacodynamics - In the context of pharmacodynamics (what a drug does to the body), the hydrophobic effect is the
major driving force for the binding of drugs to their receptor targets.
4. Consumer products - Many other industries take into account distribution coefficients for example in the formulation of
make-up, topical ointments, dyes, hair colours and many other consumer products.
5. Agrochemicals - Hydrophobic insecticides and herbicides tend to be more active. Hydrophobic agrochemicals in general
have longer half lives and therefore display increased risk of adverse environmental impact.
6. Metallurgy - In metallurgy, the partition coefficient is an important factor in determining how different impurities are
distributed between molten and solidified metal. It is a critical parameter for purification using zone melting, and
determines how effectively an impurity can be removed using directional solidification, described by the Scheil’s equation.
7. Environmental - The hydrophobicity of a compound can give scientists an indication of how easily a compound might be
taken up in groundwater to pollute waterways, and its toxicity to animals and aquatic life. Partition coefficient can also used
to predict the mobility of radionuclides in groundwater.

6. HOW IT RELATES TO DRUG ABSORPTION
• Drug absorption is determined by the drug's physicochemical properties,
formulation, and route of administration.
• In the physical sciences, a partition-coefficient (log P) or distribution-coefficient
(log D) is the ratio of concentrations of a compound in a mixture of two immiscible
phases at equilibrium. These coefficients are a measure of the difference in solubility
of the compound in these two phases.
• Partition coefficient significances how and what extent the drug will dissociate and
then cross the cellular barrier to what extent of absorption. Since drug absorption
depends on the chemical nature of the drug molecule as well as the absorption site
media pH and other buffering environment, the key role of partition coefficient is to
ensure and maintain or perform the absorption in adequate proportion within
selective biological environment. For instance, to obtain the absorption of a
lipophilic drug there should be a fatty medium where the ratio of the drug to be
designed to be more hydrophobic to cross the barrier, lipid> water=1.

7. RELATION WITH INTESTINAL pH

8. RECENT STUDIES OF PARTITION COEFFICIENT IN NEW DRUG
MOLECULE
1. Relationship of octanol/water partition coefficient and molecular weight
to rat brain capillary permeability
2. Estimation of blood-brain barrier crossing of drugs using molecular size
and shape, and H-bonding descriptors
3. Fluorine in medicinal chemistry
4. Quantitative approach to biochemical structure-activity relationships
5. Caco-2 monolayers in experimental and theoretical predictions of drug
transport
6. IAM chromatography: an in vitro screen for predicting drug membrane
permeability

9. CONCLUTION
Preformulation studies on a new drug molecule provide useful
information for subsequent formulation of a Physicochemically stable
and Biopharmaceutically suitable dosage form. Thorough
Preformulation work is the foundation of developing efficacious and
economical formulations.

10. REFERENCES
• Ansel’s Pharmaceutical Dosage forms and Drug Delivery Systems, 8th Edition,
Loyld V.Allen, Jr. Nicholas G. Popovich Howor, DC.Ansel
• The Theory and Practice of Industrial Pharmacy, Leno lachman, Herbert
A.Lieberman, Special Indian Edition 2009, CBS Publishers and Distributers Pvt.
Ltd.
• http://cdn.intechopen.com/pdfs-wm/28116.pdf
• http://lab-training.com/landing/aqueous-solubility/
• http://www.academia.edu/7720904/CHAPTER_1_Preformulation_Studies
• http://www.pharmainfo.net/reviews/preformulation-need-dosage-form-
design
• http://www.slideshare.net/manoj2205/solubility-and-partition-coefficient
• www.Wikipedia.com

11. THANK YOU