In Vitro Stability and in Vivo Absorption Studies of Colloidal Particles Formed from a Solid Dispersion System.

We investigated the physicochemical and pharmaceutical properties of a solid dispersion (SD) derived from a solution 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), hydroxypropylmethylcellulose 2910 (TC-5E) and polyoxyethylene hydrogenated caster oil 60 (HCO-60). Colloidal particles produced when the SD was dispersed into water had a mean diameter of 160 nm and contained 67-77% YM022. Powder X-ray diffractometry showed that YM022 existed in the colloidal particles in an amorphous state. The particle diameter and YM022 content remained unchanged during storage for 7 d, confirming that the colloidal solution was stable. On oral administration to rats, good absorption was observed for both the colloidal solution prepared immediately before and the sample stored for 7 d before administration. Thus, the stability of this colloidal solution of SD was confirmed by in vitro storage tests and by in vivo absorption experiments in rats.