RELEASE AND ABSORPTION CHARACTERISTICS OF CHLORPHENESIN CARBAMATE SUSTAINED-RELEASE FORMULATIONS - IN-VITRO IN-VIVO AND IN-VIVO DOG-HUMAN CORRELATIONS

The bioavailability of chlorphenesin carbamate (CPC) in sustained-release (SR) formulations exhibiting different in vitro release characteristics in dogs and humans was examined using formulations tested previously in the in vitro dissolution method. The human-dog correlation of the bioavailability of SR formulations was examined under fasting conditions, Pharmacokinetic analysis using the Wagner-Nelson procedure revealed sustained-release absorption characteristics for the SR formulations, with the exception of the immediate-release (IR) formulation as control in dogs and humans, For each of the SR formulations tested, regression analysis results of the percentage of CPC absorbed in human against that in dogs, at corresponding times, indicated a high correlation, Moreover, the correlation of the dissolution rates and bioavailabilities of these formulations in humans was also examined. Although the in vitro CPC release profiles from the SR formulations were smooth and controlled, they were too rapid when compared with the in vivo human data. However, the rank order was exactly the same between in vivo and in vitro data, and a good relationship was found after time scaling of the release data. These data imply that the release characteristics of CPC after changing of the formulations could be evaluated using the in vitro dissolution method or dogs as an animal model in place of human studies.