Enhanced Bioavailability of Phenytoin by β-Cyclodextrin Complexation

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Abstract
The interactions of the anticonvulsant phenytoin (DPH) with .alpha.-, .beta.- and .gamma.-cyclodextrins (CyD) in aqueous solution were investigated by solubility analysis, UV absorption and circular dichroism spectroscopies. The apparent stability constant of .beta.-CyD-DPH complex was the largest among the 3 CyD complexes. The solid complexes of .beta.-CyD with DPH in molar ratio 1:1 were prepared by a variety of methods (freeze drying, kneading, solvent evaporation and coprecipitation) and the interaction between host and guest molecules was confirmed by IR and X-ray diffraction measurements. The pharmaceutical characteristics of the solid complexes such as dissolution, permeation through a cellophane membrane, particle size, and in vivo extent of bioavailability were examined in comparison with those of DPH alone. The complex obtained by the freeze-drying method showed the smallest particle size with the highest dissolution rate and membrane permeability among the test powders. The complex increased significantly the levels of plasma concentration of DPH after oral administration to dogs. The increase of bioavailability of DPH by means of .beta.-CyD complexation suggested the possibility of smaller doses and fewer side effects in DPH therapy in man.