Kinetic and thermodynamic evaluation of phosphate ions binding onto sevelamer hydrochloride
Reem Elsiddig1, Helen Hughes1, Eleanor Owens1
1Pharmaceutical and Molecular Biotechnology Research Centre, Waterford Institute of Technology, Co. Waterford, Ireland.
Abstract:
Sevelamer hydrochloride is the first non-aluminium, non-calcium-based phosphate binder developed for the management of hyperphosphatemia in end stage renal diseases. It is a synthetic ion-exchange polymer which binds and removes phosphate ions due to the high content of cationic charge associated with protonated amine groups on the polymer matrix. This is the first in-depth study investigating phosphate removal in vitro from aqueous solutions using commercially available sevelamer hydrochloride at physiological conditions of phosphate level, pH and temperature. The kinetic and thermodynamic parameters of phosphate binding onto the sevelamer hydrochloride particles were evaluated in order to define the binding process. A series of kinetic studies were carried out in order to delineate the effect of initial phosphate concentration, absorbent dose and temperature on the rate of binding. The results were analysed using three kinetic models with the best-fit of the experimental data obtained using a pseudo-second order model. Thermodynamic parameters provide in-depth information on inherent energetic changes that are associated with binding. Free energy ΔG°, enthalpy ΔH°, and entropy ΔS° changes were calculated in this study in order to assess the relationship of these parameters to polymer morphology. The binding reaction was found to be a spontaneous endothermic process with increasing entropy at the solid-liquid interface.
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