Assessment of a hydroalcoholic surfactant solution as a medium for the dissolution testing of phenytoin

A buffered hydroalcoholic surfactant solution has been developed as a dissolution medium for phenytoin based on a statistically designed solubility study. A compromise between acceptable composition (relatively low additive concentrations and physiologically relevant pH), sufficient phenytoin solubility at a pH lower than thr drug's pKa (8.3) and potential discrimination power was considered in the design. The medium selected was a pH 6.8 phosphate buffer containing 12% alcohol and 0.4% Tween 80. Both phenytoin and phenytoin sodium bulk powder dissolved at a higher rate in the test medium relative to water (the USP medium for phenytoin sodium capsules). The medium proved sensitive to dissolution differences between phenytoin sodium samples with different content of the acid form. A linear relationship was obtained between the acid content and percent dissolution at 30 min for these samples. Further, the test medium could detect the reduction in dissolution of a phenytoin sodium sample subjected to storage conditions (1 month at 40 degrees C and 75% R.H.) allowing partial conversion to the acid form. From a practical standpoint, these findings may be useful in assessing the in vitro performance of both phenytoin and phenytoin sodium formulations and their dissolution stability.