Enhancement of the oral bioavailability of cinnarizine in oleic acid in beagle dogs.
The present study was an attempt to develop a new dosage form of cinnarizine, which is slightly soluble in water, using lipid as a vehicle. The solubility of cinnarizine in several organic solvents was determined. It was found that cinnarizine dissolved well in oleic and linoleic acids. The bioavailability of cinnarizine from the oral administration of an oleic acid solution in a hard capsule was investigated and compared with that of a cinnarizine tablet, using beagle dogs. When cinnarizine was administered in a capsule, the bioavailability was greatly enhanced [i.e., the maximum concentration (Cmax) and AUC values were 2.9 and 4.0 times larger than those of a cinnarizine tablet, respectively]. Meanwhile, the tmax value (the time to reach Cmax) was unchanged. The absorption of cinnarizine from an oleic acid solution was considered to depend on the action of bile salts. This was supported by the results of a dissolution test using a bile salts solution as the dissolution test medium.
D000818:Animals; D001682:Biological Availability; D002936:Cinnarizine / Q000008:administration & dosage / Q000378:metabolism*; D004285:Dogs; D007408:Intestinal Absorption; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids; D014677:Pharmaceutical Vehicles; D012995:Solubility; D012997:Solvents
D009829:Oleic Acids; D014677:Pharmaceutical Vehicles; D012997:Solvents; D019301:Oleic Acid; D002936:Cinnarizine