Using shake-flask method, distribution coefficient (Kd) 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 Kp 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. Kp of cation species is similar for both systems, while Kp 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.
|Original language||English (US)|
|Number of pages||6|
|State||Published - May 21 2007|