THE FREEZING-POINT DEPRESSION METHOD FOR THE DETERMINATION OF BINDINGPARAMETERS OF DRUGS BY POLYVINYLPYRROLIDONE AND POLYOXYETHYLENE N-DODECYLETHER

The interaction of sodium salicylate and naphazoline hydrochloride wit h polyvinylpyrrolidones having four different molecular weights (10, 2 5,40, and 360 kDa), and with the micelles of non-ionic surfactant poly oxyethylene n-dodecylethers having various numbers of oxyethylene unit s (5, 6, 7, and 8) were investigated using the freezing point depressi on method. The advantages of this method are that the binding paramete rs can be rapidly obtained by a simple procedure using a commercially available osmometer. Based on the colligative properties, the binding parameters were calculated. The data were expressed in the form of non linear Scatchard plots. The results suggested that salicylate and naph azoline were bound to two kinds of binding sites on a molecule of poly vinylpyrrolidone or to a micelle of polyoxyethylene n-dodecylether; th e primary binding site exhibited a high affinity but a low capacity fo r the drug, while the second binding site has a lower affinity and a h igh capacity; that is, the interaction on the second binding site coul d be described as non-specific binding. For the interactions of drugs with polyvinylpyrrolidone, the number of N-vinyl-2-pyrrolidone units ( monomer) that interacted with one molecule of salicylate and naphazoli ne were fairly constant, and from 10 to 14 and from 21 to 30, respecti vely. For the interactions of drugs with a micelle of polyoxyethylene n-dodecylether, the number of polyoxyethylene n-dodecylether molecules which interacted was also nearly constant at 3 to 4 and 5 to 6, respe ctively.