Dissolution behavior and bioavailability of phenytoin from a ground mixture with microcrystalline cellulose.

The ground mixture of phenytoin and microcrystalline cellulose was prepared by grinding in a vibrational ball mill. The X-ray diffraction patterns indicated the amorphous nature of the ground mixture. Comparative studies were made concerning the in vitro dissolution and in vivo absorption of fine phenytoin powder, phenytoin sodium powder, and the ground mixture. The ground mixture showed a greater dissolution rate than the fine powder and attained supersaturation in the pharmacopeial disintegration media at pH 1.2 and 7.4. In vivo absorption studies of each preparation were carried out in five subjects, using a crossover design, by measuring the urinary excretion rate of a main metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin. The blood levels of phenytoin and the corresponding urinary excretion patterns of the metabolite were determined in two subjects. The ground mixtures significantly improved the bioavailability of phenytoin. The drug was completely and rapidly absorbed after oral administration of the ground mixture. The vibrational ball milling technique for a poorly water-soluble drug with microcrystalline cellulose provides a promising way of improving the in vivo drug absorption.