In Vitro Evaluation of the Therapeutic Equivalence of Generic Sodium Polystyrene Sulfonate Formulations

Equilibrium and kinetic in vitro potassium ions (potassium chloride) binding studies were used to document bioequivalence between generic (T) and innovator (R) formulations of the cationic exchange resin, sodium polystyrene sulfonate (SPS) that is used in the treatment of hyperkalemia. The equilibrium binding studies were conducted under identical experimental conditions of constant time, and varying concentrations of potassium chloride in either simulated intestinal fluid (SIF) or water, with and without acid pretreatment of the drug product. The kinetic binding studies were conducted under constant concentrations of potassium chloride (0.3 and 3 mM) in either water or SIF with varying times of observation. Flame photometric technique was used to measure the concentration of non-bound potassium ions. Equilibrium binding studies of potassium ions to SPS in simulated intestinal fluid (SIF) did not follow Langmuir-type adsorption isotherm, otherwise, equilibrium binding studies in water have shown to obey Langmuir equation with correlation coefficient (R2) of 0.972 for both formulations. The calculated affinity (k1) and capacity (k2) binding constants were found to be (1.41; 1.25) and (3.1; 3.55 mMole/g) for generic and innovator formulations, respectively. The T/R ratios for total potassium ions bound ranged from 0.85 to 1.01 at 0.1 – 30 mM concentrations. The T/R ratios for both affinity and capacity constants were 1.13 and 0.87 respectively. In kinetic binding studies, both drug products have exhibited the same rate of exchange for potassium ions. Therefore, based on both equilibrium and kinetic data the two drug products were comparable in terms of their in vitro binding characteristics