In vivo drug release behavior in dogs from a new colon-targeted delivery system

The colon-targeted delivery capsule (CTDC), a new capsule-type dosage form for colonic delivery of drugs, was investigated for the in vivo drug release behavior in dogs. A CTDC formulation with prednisolone as a model drug and theophylline as a marker substance for gastric emptying was prepared for this study. The enteric-coated capsule (ECC) formulation with a similar composition was also prepared as the reference. Both formulations were administered to four beagle dogs, and the drug release behavior thereof was compared. Under fasted condition, ECC released prednisolone and theophylline at the same time within 1 h after the gastric emptying. On the other hand the CTDC released prednisolone at 3.2 h after the gastric emptying. Such release behavior of CTDC was approximately consistent with the results obtained from the in vitro dissolution study, suggesting that the pH-sensing and timed-release functions imparted to the CTDC can work in the gastrointestinal tract of dogs as programmed. Under non-fasted condition, however, the gastric emptying of CTDC was found to be considerably delayed, up to about 14 h, and in this case the in vivo dissolution lag time of prednisolone at the small intestine was shortened to about 1.5 h.