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.
Yano
K
K
Novel Pharma Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd, Yaizu, Japan.
Kajiyama
A
A
Yamazaki
S
S
Matsumura
Y
Y
Watanabe
K
K
Yamamoto
K
K
D000042:Absorption; D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003102:Colloids / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D012996:Solutions; D014961:X-Ray Diffraction
D003102:Colloids; D006727:Hormone Antagonists; D012996:Solutions; D001569:Benzodiazepines; C087260:YM 022