Distribution and partition coefficients of rifabutin and its ionized species in various model systems

Using shake-flask method, distribution coefficient (K_d) of an antituberculosis drug rifabutin in octanol/water system was studied as a pH function. Partition coefficients of the rifabutin ionized species (K _p) were calculated from experimental data. Apparent dissociation constants of rifabutin were determined by means of potentiometric titration in water and liposome/water systems. This allowed calculating the K_p of ionized species in the liposome/water system. It was found that for both octanol/water and liposome/water systems, most hydrophobic rifabutin species are zwitterions, while charged species are more polar. Increase in net charge of the rifabutin molecule (dication species) renders it even less hydrophobic. K_p of cation species is similar for both systems, while K_p of the zwitterion species in octanol/water exceeds the one in liposome/water system by an order of magnitude. We conclude that in an anisotropic liposome/water system, partitioning of zwitterion species to model membranes is more hindered than its partitioning into hydrophobic phase in an isotropic octanol/water system.