PhD

dissertationA mechanistic study of cholesterol monohydrate (ChM) dissolution rates (J) was conducted in the aqueous taurocholate (TC)-, taurochenodeoxycholate (TCDC)-, and tauroursodeoxy-cholate (TUDC)-lecithin (L) solutions. Based on the simple micelle-mixed micelle coexistence behavior in concentration ranges of physiological interest, these J values were analyzed and compared in terms of the effectiveness of the different micellar species. The results from the present study showed that in the TC-L system, except for that with 8 mM lecithin at Na+ level of 0.285 M where the simple and the mixed micelles were equally important, the rate constants of simple micelles (ks) were generally greater than those of mixed micelles (kM)- This is in agreement with a previous finding that the TC simple micelle is the principal species and the TC-L mixed micelle is less important in the interfacially controlled ChM dissolution kinetics. In the TCDC-L system at 0.285 M Na+, the simple micelle was equally effective in dissolving ChM as the mixed micelle at 2 mM lecithin, but became more effective with the addition of lecithin. In the TCDC-L system at 0.4 M Na+ as well as in the TUDC-L system at both levels of Na+, the mixed micelle dominated the ChM dissolution kinetics at lower levels of lecithin. However, with an increase in the lecithin concentration, the mixed micelle gradually lost its dominance and the simple micelle became the principal species at higher levels of lecithin. In the TCDC-L system at both levels of Na+, the ks value first rose dramatically with the addition of lecithin from 2 to 16 mM and then levelled off, whereas in the TC-L and TUDC-L systems, the ks values remained relatively unchanged over a wide concentration range of lecithin. These results indicate that the surface-adsorbed lecithin facilitates the dissolution of ChM by the simple micelles in the TCDC-L system but not in the TC-L and TUDC-L systems. The kM values generally decreased with an increase in the lecithin concentration at both levels of Na+ for the three bile salt-lecithin systems except for those of the TC-L system at lecithin concentrations below 8 mM where the system behaved as if the TC-L mixed micelles were nonexistent (i.e., kM approx 0)