The effect of a functional group in penicillin derivatives on the interaction with bile salt micelles studied by micellar electrokinetic chromatography

A capillary electrophoresis method is developed and validated for the characterization of the affinity and the interaction between aminopenicillanic acid (APS-H) and its derivatives with bile salt micelles. The micellar systems studied contained sodium taurocholate (NaTC) and sodium deoxycholate (NaDC). Using the retention factor k', functional group selectivity, gammaG, is defined as the ratio of the retention factor of a substituted aminopenicillanic acid (APS-R) over the capacity factor of APS-H and the difference in free energy (deltadeltaG degrees) can be used for the characterization of the affinity and interaction between drugs and micelles. The functional group selectivity is a direct measure of the interaction of the functional group with micelles. The calculated deltadeltaG degrees value gives information on the partition equilibrium and interaction between drugs and micelles. A positive deltadeltaG degrees value means that the interaction of a functional group gammaG to the APS-H leads to a decrease in the interaction with the micelles. A negative deltadeltaG degrees value, on the other hand, has the opposite meaning. The results obtained in this study exhibited that these APS-R compounds have smaller affinity to the micelles compared to unsubstituted APS-H. Furthermore, the log k' of the drugs in these systems were correlated with the log Pow in the n-octanol/water system and with log P(G) (permeation coefficient).