Dissolution Behavior and Gastrointestinal Absorption of Dicumarol from Solid Dispersion Systems of Dicmarol-Polyvinylpyrrolidone and Dicumarol-β-Cyclodextrin

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Solid dispersion systems of dicumarol-polyvinylpyrrolidone (PVP) and dicumarol-β-cyclodextrin (β-CD) were prepared by co-evaporation or freeze-drying of the drug-matrix mixture ammonium solution. Comparative studies were made on in vitro dissolution and in vivo absorption of the solid dispersion systems and dicumarol crystal powder. The dissolution rates of dicumarol were markedly increased in these solid dispersion systems in the pharmacopeial disintegration medium at pH 7.5. In vivo absorption studies were carried out in rabbits by measuring the plasma levels of dicumarol followng the oral administration of the solid dispersion systems and dicumarol crystal powder. The peak levels of the drug were observed at 4-6 h postadministration in the cases of the solid dispersion systems. On the other hand, they were observed at 2-12 h postadmini-stration in the case of dicumarol crystal powder. It appears that the modification of the dissolution characteristics of dicumarol by preparing the solid dispersion systems results in increased bioavailability of dicumarol.
公益社団法人日本薬学会の論文
1983-04-25