Evaluation of a novel colonic delivery device in vivo

Local or systemic disease may be treated by targeted delivery of drugs to the colon. This report describes the in vivo assessment in the dog of an oral dosage form designed to release drug in the colon. The system utilizes modified oral osmotic technology with enteric coating to ensure intact passage through the stomach and a placebo fraction that is released before the drug to incorporate a time delay. Absorption from the delivery system was compared with that from a colonic infusion. After an initial time delay in vitro, the release rate of metoprolol from the colonic dosage system was zero-order for 7 h before declining. After the initial lag in vivo, absorption from the colonic dosage system appeared to be zero-order on eleven out of twelve occasions. The mean absorption rate in vivo was 5.4 +/- 1.2 mg/h of metoprolol which compared with an in vitro release rate of 12.7 +/- 0.5 mg/h. The mean time lag for absorption in vivo was 5.5 +/- 0.5 h (n = 11), showing excellent agreement with the in vitro time lag of 6 h. In conclusion, this novel drug delivery system should be able to successfully release drug into the colon.