## pKa and Log P

pKa (acid dissociation constant) and log P (log partition coefficient) are two important properties of molecules. The first measures the strength of an acid in solution, while the second measures how a substance distributes itself between a hydrophobic (nonpolar) phase and a hydrophilic (polar) phase. Understanding these properties is crucial during drug product development. At Seven Star, we measure both of these properties experimentally.

## Sirius T3 Instrument (at Seven Star) to measure pKa and log P

## pKa (acid dissociation constant)

pKa is defined as the negative (base-10) logarithm of the acid dissociation constant (Ka) in a solution. It is a quantitative measure of the strength of an acid, typically expressed as:

Ka= [H+][A−]/[HA]

Where:

• [H+] is the concentration of hydrogen ions.

• [A−] is the concentration of the conjugate base.

• [HA] is the concentration of the acid.

The pKa is then given by:

pKa= −log10(Ka) = pH + log10([HA]/[A-])

## Log P

Log P is defined as the logarithm (base 10) of the partition coefficient (P) of a compound, which is the ratio of its concentrations in a mixture of two immiscible solvents, typically octanol and water:

P = [A]o/[A]w

Log P= log10([A]o/[A]w)

Where:

• [A]o is the concentration of a drug in octanol.

• [A]w is the concentration of a drug in water.

Log P (log partition coefficient) indicates how a substance distributes itself between a hydrophobic (nonpolar) phase and a hydrophilic (polar) phase. The octanol-water partition coefficient, log10(Pow), has been widely used as a measurement for defining the relative lipophilicity of a drug. The octanol-water system was selected in part because octanol is flexible, and contains a polar head and a nonpolar tail, which resembles biological membrane components. Hence, the tendency of a drug molecule to leave the aqueous phase and partition into octanol is viewed as a measure of how efficiently the drug will partition into, and diffuse across, biological barriers such as the intestinal membrane.