A Model Prediction for Chenodeoxycholate Aggregate Formation

J Pharm Sci. 2017 May;106(5):1391-1395. doi: 10.1016/j.xphs.2017.01.017. Epub 2017 Jan 24.

Abstract

A relationship between the chenodeoxycholate (CDC) monomer concentration and the total concentration of CDC was established using a kinetic dialysis technique. Meanwhile, the sizes of the formed simple CDC micelles were measured by a quasielastic light-scattering (QLS) technique to be nearly constant. The QLS results led to a suggestion for equilibrium models of CDC aggregate formation. According to the established relationship and the suggested models, the best curve-fitting model was selected by a least-squares technique. Furthermore, the model parameters were quantified. Based on the quantified parameters, at a minimum detectable concentration of simple CDC micelles to be ∼0.2 mM, an appropriate model corresponding concentration of CDC monomers was estimated to be ∼3.08 mM. This value is consistent with a minimum monomer CDC concentration of ∼3.13 mM for simple CDC micelle formation estimated according to the present QLS detection and the model prediction. The consistency confirms the model prediction that at a low CDC monomer concentration (<3 mM), the concentration of stable CDC dimers is much higher than that of simple CDC micelles but the contribution of simple CDC micelles to the total CDC concentration cannot be negligible.

Keywords: curve-fitting; kinetic dialysis technique; quasielastic light-scattering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cathartics / chemistry
  • Cathartics / metabolism
  • Chenodeoxycholic Acid / chemistry*
  • Chenodeoxycholic Acid / metabolism*
  • Forecasting
  • Models, Chemical*
  • Protein Aggregates / physiology*

Substances

  • Cathartics
  • Protein Aggregates
  • Chenodeoxycholic Acid