PARTITION COEFFICIENT

PCT200 LAB – Physical Pharmacy

Pharmacy, Chemistry and Clinical Pharmacy Program
University of the Immaculate Conception
Davao City

Laguiab, Shariquen Reyhana

Grana, Lemuel Giovanni
Letrero, Clarissa Faith
Lancita, Alyssa Anne
Juntilla, Shanyn

Mrs. Ruby Felina D. Mahinay, RPh

Instructor
BACKGROUND

Partition coefficients are defined as the concentration ratio of a chemical between

two media at equilibrium. The media can be gases such as air, liquids such as water or
olive oil, or complex mixtures such as blood or other tissues (Johanson, 2010). Molecular
partitioning occurs when an organic compound dissolves in each of two immiscible
solvent phases and is measured by the partition coefficient or distribution coefficient
which is the ratio of concentrations of the compound in a mixture of the two immiscible
phases at equilibrium. This ratio is therefore a measure of the difference in solubility of
the compound in these two phases (Speight, 2017).
The importance of partition coefficient has different applications. In relation to drug
absorption, drugs with high partition-coefficient value can easily permeate through
biological membrane. The diffusion of drug molecules across rate-controlling membrane
or through the matrix system essentially relies on the partition-coefficient. Drugs having
lower partition-coefficient value are not suitable for translating in to oral controlled release
formulations and drugs that have higher partition-coefficient are also poor candidates for
oral controlled formulations (Madan et al., 2018).
In relation with intestinal pH, ionic drugs depending on the pH partition into charged
and noncharged species, and can be measured at various pH values. For ionizable drugs,
the more lipid-soluble unionized (uncharged) form is the form that most readily crosses a
lipid bilayer. The pH determines the extent of ionization, the pH at absorption or
permeation sites plays a large role in determining the passive diffusion of a drug across
a lipid bilayer (Amiji et al., 2016).
Furthermore, it is required in pre-formulation students because 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.
In this laboratory activity, we aimed to define the basic concepts of partition
coefficient and its application in drug permeation and to determine the partition coefficient
of succinic acid with the use of two solvents, the distilled water and butanol.
 METHODOLOGY
The following methods were used in the Partition Coefficient activity:
A. MATERIALS

The following materials were used: Two 100-mL separation funnels, titrimetric flasks,
burette, pipette, and six beakers

B. PREPARATION OF SAMPLE
Three substances, Butanol, Water, and Succinic Acid, were utilized in experiment.
The Butanol and Water served as the two partially immiscible solvents, and the
Succinic Acid as the third substance added to the system. Two different setups were
prepared with varying volumes of three liquids.
In the first separation funnel, 20-mL of Succinic Acid was incorporated to 15-mL 1-
Butanol.
C. OBTAINING THE AQUEOUS PHASE AND ORGANIC PHASE

Water was carefully poured into a beaker by slightly opening the separation
funnel’s valve and the organic substance was reserved for the next part. After the first
titration, the organic phase was obtained by following the same procedure.

The water solution that has been poured into a beaker was transferred into two
Erlenmeyer flasks containing 5mL per flask using a pipette. Another two Erlenmeyer
flasks were used for the organic phase.

In the second set-up, 15 mL of Butanol and 15 mL of water were placed in the

separation funnel. Succinic acid was the third substance added with a volume of 10
mL.

The prepared solutions were mixed for 20 minutes and allowed the mixture to be
separated into two layers: lower layer is water and upper layer is butanol.

D. TITRATION
In the two titration setups, the titrant was the Sodium Hydroxide and the indicator
was Phenolphthalein. The anticipated color endpoint was light pink. When the
endpoint has been reached, we read the volume of the NaOH that was used up to
reach the designated endpoint. The same procedure was supposed to be done with
the upper layer of the mixture and record the volume of the remaining titrant.
 RESULTS

Table 1. Composition of Partition Coefficients

Funnel No.1 Succinic Acid (mL) Distilled Water (mL) 1-Butanol
(mL)
1 20 - 15
2 10 15 15

Table 2. Volume of titrant used, Concentration of Organic and Aqueous Phases, and
Partition Coefficient
Meas. Volume of titrant (VT) mL Corg Cwat ki
No. 1-butanol Water mol mol
V1, V1, V1 V2, V2, V2 dm-3 dm-3
1mL 2mL (Ave) 1mL 2mL (Ave)
mL mL
1 3.9 2.5 3.2 11 12.55 13.275 0.16 0.332 0.048
2 3.15 2.2 2.65 11 5 8 0.266 0.8 0.330
3 3 2.65 2.675 11 11 10.5 0.0134 0.053 0.250
4 1.6 2.1 1.850 9.13 7.4 8.26 0.0093 0.0413 0.224

CALCULATIONS

Molar Concentration of Octanol

Molar Concentration of Water

Partition Coefficient
Standard Deviation

DISCUSSION

Two liquids are said to be immiscible if both are completely insoluble in each other.
Such system consists of 2 phases where the liquids do not interact with each other.
Though classified as immiscible, there is still some degree of mutual solubility. 1-butanol
is considered as partially soluble in water. Water is polar as so is the -OH group in 1-
butanol. The carbon chain present in 1-butanol is nonpolar, which make it repel polar
molecules such as water. The third substance introduced to the system is succinic acid
which will act as the solute that will distribute to both solvents. Succinic acid is a four-
carbon carbon chain with two carboxylic acid groups on either end. The electronegative
oxygen in the carboxylic acid produces H-bonds, making the compound polar and thus,
making it soluble in water and in 1-butanol. The polarity of succinic acid allows it to be
distributed in both phases. High polarity solute has a higher affinity to aqueous phase
while low polarity solute has a higher affinity to the organic phase. Succinic acid has a
hydrogen atom bonded to oxygen atom and can easily form hydrogen bonding with the
surrounding water molecules. Due to this interaction succinic acid is more concentrated
in water rather than in the organic phase.

Partition Coefficient:

In high polarity compounds, which is more concentrated in the aqueous phase, the
partition coefficient is a relatively small number over a relatively large number. This will
result in a particularly small partitioning coefficient. However, in low polarity compounds
in which are more concentrated in the organic phase, the partition coefficient is a large
number over small number resulting to a large Kp. The values should be different from
one another as possible. The more different the values are, the more effective the liquid-
liquid extraction will be.
 CONCLUSION

In this laboratory experiment performed, the partition coefficient of both the

samples succinic acid in water and octanol was identified. Theoretically, the succinic acid
should partition more in water and must readily ionized in aqueous solutions. However,
human errors are obtained during the laboratory experiment. The second part of the
procedures we're not able to be. performed due to lack in knowledge about the
experiment. The recorded interpretation above is only for the part 1 of the experiment.
Thus, the results also lack in data for interpretation. Moreover, the partition coefficient is
significant in the field of pharmacy, because most of the pharmaceutical products used
today are mostly solvents. Using the partition coefficient, we can predict the solubility of
the solvent of two phases in the body; on its characteristics as a hydrophilic or a lipophilic
phase.
REFERENCES

McQueen, C. A. (2010). Comprehensive Toxicology. Auburn, AL, USA: Harrison

School of Pharmacy, Auburn University.
Speight, J. G. (2013). Environmental Organic Chemistry for Engineers.
Liebermann et al. (2012). The Theory and Practice of Industrial Pharmacy.
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