Physicochemical Stability of Pharmaceutical Phosphate Buffer Solutions.I. Complexation Behavior of Ca(ll) with Additives in Phosphate Buffer Solutions

Abstract

It was found that precipitation in phosphate buffer solutions was mainly caused by formation of aluminum phosphate and calcium phosphate, which was attributed to the reaction between Ca(II) and Al(III)from pH-adjusting agents such as alkali hydroxides or carbonates and phosphate. In the present experiment, a model system of Ca(II)-phosphate was established and optimal conditions for prevention of the precipitate or stabilization in buffer solutions were investigated on the basis of the precipitation-prevention factor, Rca [a molar ratio of complexed Ca(II) to additive at a complete dissolution point of Ca(II), and the stability constant for the 1:1 Ca complex presumed. EDTA was the most favorable for complexation of Ca(II) in phosphate buffer solutions (pH 6-9), but the complexation of Ca(II) with other additives generally became weak with increasing pH and temperature. The complexation of Ca(II) with condensed phosphates was relatively strong, followed by that with citric acid. In the case of other carboxylic acids, high concentrations were required for complexation of Ca(II). On the basis of the complex stability constants calculated, it was found that complexation of Ca(II) with additives was remarkably inhibited by the presence of phosphate buffer.