Buffer capacity and precipitation control of pH solubilized phenytoin formulations

The main objective of this investigation is to develop a phenytoin (DPH) intravenous formulation that does not precipitate upon dilution. The effect of the buffer capacity at pH 12 of several DPH formulations on the extent and lag-time of DPH precipitation upon dilution with Sorensen's phosphate buffer (SPB) is evaluated. DPH precipitation was evaluated by means of static and dynamic in vitro dilution methods. It is shown that an increase in the formulation buffer capacity decreases substantially the extent of DPH precipitation and increases the lag-time for precipitation. In addition, a comparison between static and dynamic in vitro methods to measure precipitation is presented.