Powder coating mixture of a novel anxiolytic, Y-23684: dissolution characteristics and bioavailability.
A powder coating mixture was investigated with a view toward improving the dissolution property of the anxiolytic 2-(4-chlorophenyl)-5,6-dihydro-[1]benzo-thiepino-[5,4-c]-pyrida zin-3(2H)-one 7-oxide (1), which was barely water soluble. The powder coating mixture in various ratios of 1 and cornstarch was prepared in an automated mortar. Among these mixtures, at the optimum ratio of 1 and cornstarch (2:1, 67% drug content), the powder coating mixture gave a maximized effect for solubilizing 1 on the bases of stability and solubility. Conventional granules were made from the 67% powder coating mixture. The granules showed an excellent absorption profile in beagle dogs. The mechanism of the solubilizing effect resulting from a pharmaceutical process was also discussed.
Pharmaceutical Development Analytical & Pharmaceutical Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
H
H
Samemoto
I
I
Yamada
T
T
Yata
K
K
Ogawa
D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D001582:Benzothiepins / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D008297:Male; D011208:Powders; D011724:Pyridazines / Q000493:pharmacokinetics*; D012995:Solubility
D014151:Anti-Anxiety Agents; D001582:Benzothiepins; D011208:Powders; D011724:Pyridazines; C074367:Y 23684