pH Partition Hypothesis – Gastrointestinal #Absorption of Drugs

pH Partition Hypothesis is one of the PHYSICOCHEMICAL, PHARMACEUTICAL, AND BIOLOGICAL CONSIDERATIONS IN GIT ABSORPTION OF DRUGS. This can be understood clearly as a sub topic of pH Partition Hypothesis Factors Affecting GastroIntestinal Absorption of Drugs.


As we all know Drugs that are weakly acidic or weakly basic generally undergo ionization and their absorption can be explained by the drug’s pKa, lipophilicity, and GI pH.
In contrast to the capillary walls, cell membranes were able to act as effective barriers during the absorption of drugs. MH Jacobs in 1940 reported the cellular permeation characteristics of weakly electrolytic solutions designated the permeability of nonionic species quantitatively. After his studies, many studies followed and led to the hypothesis of pHpartition theory (Maza´k and Nosza´l, 2014). This theory compared the dissociation constant, lipophilicity, and pH with absorption. Knowledge of the exact ionization of the drug is important as the unionized form has greater lipophilicity than its ionized counterpart. pH partition hypothesis can be explained by the HendersonHasselbach equations. Check the image for the HendersonHasselbach equations for acids and HendersonHasselbach equations for bases.

For acids,

pH partition hypothesis can be explained by the HendersonHasselbach equations as follows:

pH Partition Hypothesis Factors Affecting GastroIntestinal Absorption of Drugs

And for bases,

Most of the absorption studies confirmed the accuracy of this hypothesis. However, there are certain limitations to it. These are related to the unstirred water layer, the microclimate
pH, and the mucous coat adjacent to the epithelial cells.

Note :

For drugs to cross the lipid membrane they need to have some solubility in the lipid membrane and to get dissolved in GIT they have to have aqueous solubility. Unionized forms can undergo passive diffusion to get transported as they has lipid solubility, but the ionized form is required for the solubility of the drug in the GIT. Drugs that are weakly acidic and weakly basic, generally undergo ionization (Yang et al., 2012).

Mostly drugs are developed as salts of weak bases or weak acids to have good solubility and absorption. These salt forms are ionizable and therefore their solubility is pH dependent. The following equations can be derived to understand the pH-dependent solubility of the drugs from the dissociation of monoprotonated conjugate acid from a base.

Leave a Comment