1997 年 57 巻 2 号 p. 95-101
We investigated the effect of a 3-component solid dispersion system on the gastrointestinal absorption of the poorly water-soluble drug (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl) urea (YM022) in beagle dogs. Absorption of YM022 from the 3-component system was markedly improved compared to that when administered using the β-form crystal, amorphous form and 2-component solid dispersion. The concentration of dissolved YM022 at 20°C was determined in purified water, JP 13 1st disintegration test fluid, and 0.05, 0.1 and 0.5% solutions of either polyoxyethylene hydrogenated caster oil 60 (HCO-60) or hydroxypropylmethylcellulose 2910 (TC-5E), both of which are components of the YM022 solid dispersion system. In HCO-60 aqueous solution, YM022 concentration in the amorphous form and 2- and 3-component solid dispersion systems was markedly higher than that in stable crystalline form. On succesive dispersion of the 3-component system in purified water with the replacement of solution with fresh purified water at each dispersion, the initial high level of YM022 concentration was maintained. These findings indicate that interaction among YM022, TC-5E and HCO-60 in solid and solution states may result in the improvement of YM022 bioavailability.
