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

Abstract

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).

Analytical tools for the physicochemical profiling of drug candidates to predict absorption/distribution

“…Highly hydrophilic neutral compounds such as acetone are used as EOF markers, whereas highly lipophilic compounds such as dodecaphenone are selected as micelle markers. Good linear correlations were found between log k (measured by MEKC) and log P oct for a wide variety of compounds and conditions [103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122]. However, congeneric behavior was observed [108,116] and confirmed by LSER analyses, which demonstrated differences in H-bond basicity and dipolarity/polarizability for partitioning into SDS micelles or the 1-octanol/ water system [98].…”

The influence of 3α,7α-dihydroxy-12-keto-5β-cholanate on gliclazide pharmacokinetics and glucose levels in a rat model of diabetes

“…Bile salts have been shown to increase intestinal absorption of insulin (14), cefpirom (15) and many other drugs. It has been shown that MKC improved the absorption and blood-brain barrier penetration of morphine and quinidine (16) as well as the hypoglycemic effect of insulin (17).…”

Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions

“…Good correlation between MEKC log k 0 for six -blockers to Caco-2 cell permeability was also shown, as was permeation through the intestinal segment of rat ileum and rat colon data (Ö rnskov et al 2000). Good correlation with permeation across a dodecanol collodium cell membrane system has also been reported (Mrestani et al 2001). MEKC migration data were correlated to Caco-2 cell permeability data for -blocker model compounds (Detroyer et al 2003).…”