A. Roda et al., EXPERIMENTAL EVALUATION OF A MODEL FOR PREDICTING MICELLAR COMPOSITION AND CONCENTRATION OF MONOMERIC SPECIES IN BILE-SALT BINARY-MIXTURES, Journal of pharmaceutical sciences, 84(5), 1995, pp. 593-598
The critical micellar concentration (cmc) values of some mixed systems
containing two bile salts were determined by a maximum pressure bubbl
e method and compared with those derived from a theoretical model deve
loped for nonionic surfactants to assess the applicability of this mod
el to such systems. Some assumptions on which the presumed validity of
this model was based are discussed. The following binary mixtures wer
e investigated: sodium chenodeoxycholate with cholate, ursocholate and
ursodeoxycholate, either unconjugated or conjugated with taurine and
glycine at different mole fractions (0, 0.25, 0.5, 0.75, 1) in 0.15 M
NaCl. For these mixtures, experimentally determined data were in good
agreement with values predicted by the theoretical model: both the cmc
and the surface tension at this concentration of the mixtures were in
termediate between those of the two pure bile salts; also, as the tota
l bile salt concentration increased, the mixed micelles became enriche
d with the bile salt having the highest cmc, whereas the total monomer
activity, determined by a potentiometric method employing a bile salt
-selective electrode, increased only slightly. To test this model in a
n in vitro system, surface tension was also measured in ox bile sample
s that were enriched by 50% with sodium ursodeoxycholate, chenodeoxych
olate, or their taurine amidates. The cmc and the surface tension at t
his concentration of the artificial bile increased when enriched with
a bile salt with a cmc higher than that of endogenous salts (e.g. urso
deoxycholate versus taurocholate), whereas the reverse occurred for mi
xtures enriched with a bile salt with a lower cmc, such as chenodeoxyc
holate. The applied theoretical model could be utilized in the design
of new synthetic bile salt analogs because it can predict their behavi
or in mixture with physiological bile salts.