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

The exchange reaction between sulfopropyl-dextran ( SephadexM C - 25) and Propranolol Hydrochloride ( Prop - HC1 ) as a model drug was studied. Binding experiments were carried out using a disolution 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 reacted within approximately 12 min and was nicely described by the Langmuir eqaution for low degree of occupation of binding sites ( concentrations of Prop - HC1 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 SephadexM C - 25 upon addition of Prop HC1 solution sqeezes considerable amounts of the drug molecules out of the complex. Although the Langmuir fit is excellent, it cannot reveal information about the equilibrium.