A New Method for Determination of Stability Constant of Cyclodextrin Complexes by Membrane Permeation Technique

Abstract

It is important to determine the stability constant (Km:n defined by Eq. 1) of cyclodextrin (CyD) complexes with great accuracy, because this parameter is useful for the estimation of changes in physicochemical and biopharmaceutical properties of the guest molecule included in the CyD cavity: $$ Kc = \frac{{[complex]}} {{[CyD]_m \cdot[guest]_n }} $$ (1) where [complex], [CyD] and [guest] are molar concentrations of the complex and free CyD and guest molecules, respectively, and m and n are binding mole numbers of CyD and guest in the complex, respectively. There are many methods for determination of the stability constant of CyD complexes, using various techniques such as solubility, potentiometry, kinetic and spectroscopic methods [1]. All these methods are based principally on titrating certain physical or chemical properties of the guest with CyD, and analyzing the CyD concentration dependencies by means of Benesi-Hildebrand equation, Lineweaver-Burk equation or their modified forms. Therefore, the change in physicochemical property of the guest molecule has to be measured as a function of CyD concentration. In this study, we developed a simple and reliable method for the determination of stability constant of CyD complexes by analyzing permeation rate of the guest in the presence of CyD through a cellophane membrane.