In vivo evaluation of ethyl cellulose microcapsules containing ampicillin using rabbits, beagle dogs and humans.

Ampicillin, an orally administered antibiotic, was microencapsulated with different viscosity grades of ethyl cellulose (10, 50 and 100 cps EC) and was orally administered to rabbits, beagle dogs and humans. A significant sustained release pattern was observed in rabbits. While a significant decrease in the area under the plasma concentration curve occurred, and the sustained release pattern was not obtained in beagle dogs. In humans, the extent of the sustained release was intermediate between the pattern observed in beagle dogs and rabbits. The treatment of data by log-log plots yielded a linear relation between half lives of dissolution of ampicillin from microcapsules in vitro (T50) and the ratios of pharmacokinetic parameters of microcapsules to those of powder. In order to explain the difference in the sustained release pattern of rabbits, beagle dogs and humans, a pharmacokinetic model, considering gastric-emptying and intestinal-transit rates of drug formulations, was established and the pharmacokinetic consideration was done on the basis of the model. It seems that success in sustained release of a drug depended on the magnitude of the gastric-emptying and intestinal-transit rate constant (kgi) of microcapsules, in the case of a drug with a small absorption rate constant (ka) as observed with ampicillin. The magnitude of kgi was thought to be in the order of beagle dogs, humans and finally rabbits.