m.pharm analysis, pharmaceutical analysis, food analysis, cosmetic analysis and evaluation, modern bio analytical techniques, advanced pharmaceutical analysis, phamaceutical validation

1. SUBJECT : APA
KARNATAKA COLLEGE OF PHARMACY
TOPIC : LOG P
SUBMITTED BY: SUBMITTED TO:
ABHISHEK DR. C. SREEDHAR
M. PHARM 1ST SEMESTER PROF. AND HOD
DEPT. OF PHARMACEUTICAL ANALYSIS DEPT. OF PHARMACEUTICAL ANALYSIS
KARNATAKA COLLEGE OF PHARMACY KARNATAKA COLLEGE OF PHARMCY
BANGALURU BANGALURU
KARNATAKA COLLEGE OF PHARMACY
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2. CONTENTS
 INTRODUCTION
 DETERMINATION OF PARTITION COEFFICIENT
 APPLICATION
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3. INTRODUCTION:-
• The partition coefficient is defined as the ratio of concentrations
of a compound in a mixture of two immiscible solvents at equilibrium
• The partition-coefficient decides the hydrophilic & lipophilic nature of
any drug or medicine.
 The formula of log p is:-
partition coefficient(p) = conc. of Drug in Organic phase
conc. of Drug in Aqueous phase
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4.  This ratio is therefore a measure of the difference in solubility of the
compound in these two phases.
 The partition coefficient generally refers to the concentration ratio of
unionized species of compound.
 In the chemical and pharmaceutical science both phases usually are
solvents. Most commonly, one of the solvents is water, while the second
is hydrophobic, such as octanol.
 When one of the solvents is water and the other is a non-polar solvent,
then the log P value is a measure of lipophilicity or hydrophobicity.
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5. Partition coefficient data of some compounds
 The compound with negative Log p value are compound with a grater
solubility in water than non-polar organic phase but the polar
compounds that are well solubility in aqueous phase
Components Log P T (°C)
Acetamide -1.16 25
Methanol -0.81 19
Formic acid -0.41 25
Diethyl ether 0.83 20
p-Dichlorobenzene 3.37 25
Hexamethylbenzene 4.61 25
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6. DETERMINATION OF PARTITION COEFFICIENT
It can be measured by using following methods
 Shake flask method.
 HPLC method.
 pH metric method
 Computational determination of log P
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7. A. Shake flask method:-
 It is a common method.
 Direct method experimentally determine the log p of compound is called shake flask
method.
 some amount of drug is added, dissolved in octanol & water. Temperature must be
constant.
PROCEDURE:-
 Twosolution are mixed. vigorous shaking.
 After which water and 1-octanol phase are allowed to settle for 24 hours Two phases
are separated.
 Conc. of compound in each layer determined by suitable analytical method.
 The distribution of solute is measured bymethods.
1. UV-Visible spectroscopy
2. Carrier free radiotracer
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8. B. HPLC method:-
 Compounds with known Log P are injected onto a C18 reverse phase HPLC column and
their capacity factors used to create a calibration curve.
 Unknown compounds are then injected, and their capacity factors used to predict log P
.
C. pH metric:-
 This technique determine lipophilicity pH profiles directly from a single acid-base
titration in a two-phase water-organic solvent system.
 Hence, a single experiment can be used to measure the log P
.
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9. D. Computational determination of log P:-
 The method used by these software packages are generally on hydrophobic
fragmental constant. Developed by ReKker ,Hansch and Leo.
 Effort has gone into developing software that can calculate Log P values based on
molecular structure.
 Log P predicting software is common and widely used,
 Log p calculating commands can also often be found on molecular structure drawing
software,
 Log p compound nationally breaking the compound up into series is known
fragment.
 Computational determination log p is very convenient,
 Calculated log p values more reliable and accurate.
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10. Application of partition coefficient:-
 In pharmacokinetics, log P has a strong influence on ADME properties
of a drug.
 In environmental science partition coefficient can be used to predict
the mobility of radioactive compounds in groundwater and hence
study water pollution and its toxicity to animals and aquatic life.
 In metallurgy, partition coefficient is an important factor in determining
how different impurities are distributed between molten and solidified
metal.
 In FMCG, partition coefficient is taken into account e.g.in the
formulation of topical ointments, dyes, hair colors, etc.
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11.  log P determination of
levofloxacin:-
 Determined by shake flask method in n-octanol: water system
 10mg of drug is added into 50ml each of n-octanol and water
 The mixture is shaken for 24 hours until equilibrium is reached
 Phases are separated using a separating funnel, filtered and
suitably diluted
 Absorbance is measured at 258nm using UV spectrophotometer
 Partition coefficient (P) is calculated using:
P = Co
Cw
and hence log P can be calculated.
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12. THANK YOU
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