Mechanistic Study of Cholesterol Monohydrate Dissolution in Aqueous Micellar Surfactant and Sodium Chenodeoxycholate Solutions.

The purpose of this study was to more broadly examine the influence of electrical factors and factors other than electric charge in the interfacially controlled dissolution of cholesterol monohydrate in a nonionic surfactant micellar solutions. Limited baseline studies were also conducted in sodium chenodeoxycholate (NaCDC) solutions, a simple bile acid and the findings from the two systems were compared. The results may be summarized as follows: (1) In the dissolution rate studies in Renex-690 (a polyoxyethylene nonylphenol ether) the interfacial resistance R was found to be relatively constant over a wide concentration range with and without sodium chloride. This constancy of R supports the micelle collision mechanism since the free solute mechanism would be expected to show a direct proportionality between R and the solubilizer concentration. Moreover, these studies showed that Renex-690 (a neutral micelle) itself may be associated with slow interfacial kinetics. (2) In the dissolution rate studies at constant Renex/benzalkonium chloride (BC) and Renex/sodium dodecyl sulfate (SDS) surfactant ratios, when the counterion contribution from the ionic surfactant is taken into account the R values were found to be essentially superimposable over a range of solubilizer concentration. Similar patterns were observed with long chain alkylamines and the fatty acids at pH conditions where these surfactants exist in their charged forms. (3) At low electrolyte levels, in the case of BC or SDS/Renex-690, the dissolution kinetics data was essentially quantitatively described by the physical model employing the classical Smoluchowski flocculation theory of colloidal particles and the Verwey and Overbeek theory of electrical double layer repulsion and dispersion attraction. When the electrolyte levels are high, however, the kinetics of dissolution become controlled by convective diffusion in the aqueous boundary layer. (4) It was found that uncharged amphipathic compounds were able to enhance the dissolution kinetics beyond the maximum rates found with Renex-690 alone. These results and other results with charged surfactants were examined by considering factors associated with the micellar structure (hydrophilicity/hydrophobicity of the Renex-690 micelle) and possible factors associated with cholesterol crystal surface. (5) Interestingly, striking similarities were found in the results obtained with NaCDC system containing different electrolyte type and concentration and Renex/ionic surfactant systems.PhDPharmacy sciencesUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/159001/1/8224959.pd