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.