Loading of Propranolol-H+ onto SP Sephadex C-25 Studied by Isothermal Calorimetry and Spectroscopy

The exchange reaction between sulfopropyl-dextran (Sephadex™ C-25) and propranolol hydrochloride (prop-HCl) as a model drug was studied. Binding experiments were carried out using a dissolution tester and photometric quantification of the amount of drug bound. The thermodynamic parameters of the binding reaction were derived by isothermal titration calorimetry (ITC) and equilibrium studies. Equilibrium was reached within approximately 12 min and was nicely described by the Langmuir equation for low degree of occupation of binding sites (concentrations of prop-HCl in equilibrium up to 3.6 mmol/L) with respect to the exchange capacity (2.0 mmol/g ion exchanger). However, the heat effects measured in the ITC experiment for step-wise addition of drug solution surprisingly increased for the first injections up to a maximum and only thereafter decreased. The heat effects do not exclusively represent the exchange reaction, but rather include a more complex pattern of reactions: shrinking of SP Sephadex™ C-25 upon addition of prop-HCl solution squeezes considerable amounts of the drug molecules out of the complex. Although the Langmuir fit is excellent, it cannot reveal information about the equilibrium.