Mechanisms of cholesterol monohydrate dissolution in aqueous taurocholate-, taurochenodeoxycholate-, and tauroursodeoxycholate-lecithin solutions—correlation between micellar species and dissolution rates

Abstract

A complete mapping study of the cholesterol monohydrate (ChM) dissolution rates ( J) has been completed for the aqueous taurocholate (TC)-, taurochenodeoxycholate (TCDC)-, and tauroursodeoxycholate (TUDC)-lecithin (L) systems over a wide range of bile salt concentrations at seven levels of lecithin (0, 2, 4, 8, 16, 24, and 32 m M) and two levels of added NaCl (0.20 and 0.40 M). From equilibrium dialysis experiments, the simple micelle—mixed micelle coexistence equilibria were quantified and the micellar species concentrations determined. The rate constants for the simple micelle ( k s) and for the mixed micelle ( k M) at each level of lecithin were deduced from the J values and the micelle concentrations. The following were the important conclusions. First, these studies have confirmed our previous finding that the TC simple micelle is the principal species and the TC-L mixed micelle is much less important in the interfacially controlled ChM dissolution rates in the TC-L system. In the TCDC-L and TUDC-L systems, the relative importance of the simple and the mixed micelles depends on the lecithin and the total Na + concentrations in the dissolution medium. However, at physiological levels of lecithin (i.e., 24 m M and above), it is always the simple micelle which dominates the ChM dissolution kinetics in both systems. In the TCDC-L system, the k s value first increased dramatically with the addition of lecithin from 2 to 16 m M and then leveled off. In the TC-L system, the k s value remained relatively unchanged over a wide concentration range of lecithin. These results were interpreted to mean that surface-adsorbed lecithin facilitates the TCDC simple micelles, but not the TC simple micelles, in ChM dissolution. Lecithin facilitation of TUDC simple micelles was found to be intermediate. The mechanisms by which surface-adsorbed lecithin may facilitate the attack of ChM crystallites by simple micelles remain to be clarified. The k M values generally decreased with increasing lecithin concentration for the three bile salt-lecithin systems. This decrease in k M with the addition of lecithin may be related to the molecular composition (the K value) and the increasing stability of the mixed micelles at higher lecithin levels. As previously noted, the addition of lecithin to a constant level of TC results in a decrease in the ChM dissolution rate despite a linear increase in the equilibrium solubility. However, in the TCDC-L system, the ChM dissolution rate first rises with increasing lecithin to 16 m M lecithin and then levels off. These differing patterns for the TC-L and the TCDC-L systems are explained on the basis of the simple micelle-mixed micelle coexistence phenomenon and the relative effectiveness of the micellar species in dissolving the ChM crystallites.