Dissolution Behaviors and Gastrointestinal Absorption of Phenytoin in Phenytoin-Polyvinylpyrrolidone Coprecipitate

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Phenytoin-polyvinylpyrrolidone (PVP) coprecipitate was prepared. The X-ray diffraction spectra indicated that phenytoin in the coprecipitate did not exhibit its crystalline property. Comparative studies were made on the in vitro dissolution and the in vivo absorption of the coprecipitate and phenytoin alone. The dissolution rate of phenytoin was markedly increased in the phenytoin-PVP coprecipitate in the pharmacopoeial disintegration media at pH 1.2 and 7.5. The concentration of phenytoin released from the coprecipitate reached supersaturation within a few minutes in dissolution studies. The solution remained supersaturated for a long period. The dissolution rate of phenytoin in the coprecipitate was greater when the ratio of drug to PVP was smaller and when PVP of smaller molecular weight was used for the preparation of the coprecipitate. In vivo absorption studies of each preparation was carried out in five subjects by measuring the urinary excretion rate of free and conjugated forms of a main metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin. Excretion rate and cumulative amount of the metabolite excreted following the oral administration of the coprecipitate were greater than those of phenytoin alone. The plasma levels of phenytoin following the administration of the coprecipitate were almost twice as high as those of the phenytoin alone, in rabbits. It was indicated that the drug was rapidly and almost completely absorbed following oral administration of the coprecipitate.
公益社団法人日本薬学会の論文
1978-10-25

Dissolution Behaviors and Gastrointestinal Absorption of Phenytoin in Phenytoin-Polyvinylpyrrolidone Coprecipitate

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