Evaluation of the bioavailability of a solid dispersion of phenytoin in polyethylene glycol 6000 and a commercial phenytoin sodium capsule in the dog.

In this study a solid dispersion of phenytoin in polyethylene glycol 6000 was prepared by the melt method. The content uniformity of the dispersion indicated a range of 98.7-102.0%. X-ray crystallographic data showed no changes in the crystalline structure of the phenytoin in the dispersion when compared with that in the bulk reagent. Scanning electron micrographs of the dispersion show a reduction in the size of the crystals when compared with the bulk reagent. The commercial product and the dispersion were compared using the USP criteria for the prompt phenytoin sodium dissolution test. The salt dissolved at a rate four times greater than the dispersion. Bioequivalency comparisons between the dispersion containing phenytoin and the commercial prompt phenytoin sodium were studied in six mixed-breed dogs. All samples were analyzed using a commercial enzyme immunoassay system. Statistical analysis of the plasma levels obtained from the animal studies indicate no significant differences (p greater than 0.05) between area under the curve, maximum plasma concentration, and time to peak for the commercial salt and the acid formulation.