Abstract
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]-pyridazin-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 cptimum 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 phatmaceutical process was also discussed.
