The effects of storage and shaking on the settling properties of phenytoin suspension

Abstract

Phenytoin suspension (PHY-S) is reported to settle, resulting in uneven drug distribution and variable patient dosing. We designed this study to determine the rate of settling and the amount of agitation needed to resuspend the preparation. To determine the rate of settling, we thoroughly shook three bottles of PHY-S and then left them undisturbed. We took samples from the top and bottom of each bottle with a microsyringe at 15 minutes, 1, 6, 12, 24, 48, and 72 hours, and 1, 2, 3, 4, and 5 weeks. We simulated patient administration with daily doses that were measured under good, fair, and poor shaking techniques. We analyzed samples after every tenth dose. After complete resuspension the active ingredient in PHY-S settles at a very slow rate. We found no differences in concentration between the top and bottom until the fifth week in the bottles thoroughly shaken and left undisturbed. Minimal agitation is required to resuspend PHY-S. The well-shaken and poorly shaken bottles in the patient simulation phase exhibited no differences in concentrations whereas the unshaken bottle had differences throughout the study period. Problems thought to be associated with PHY-S may be related to compliance and inaccurate measuring devices.