IN-VIVO PERFORMANCE OF TIME-CONTROLLED EXPLOSION SYSTEM (TES) IN GI PHYSIOLOGY REGULATED DOGS

In vivo oral absorption study of time-controlled explosion system (TES ), using gastrointestinal (GI) physiology regulated dogs, was carried out to predict the feasibility in humans. TES is characterized by rapi d drug release with a pre-programmed lag time, which can provide a pro grammed release system synchronized with circadian rhythm (e.g. asthma attack in the morning), a colon targeting system and a sustained rele ase system with different lag times. In this study, TES containing dic lofenac sodium with different lag times of 3 and 6 h (TES-3h and TES-6 h) were prepared. TES-3h exhibited good performance in all six GI:phys iology regulated dogs without remarkable reduction of AUC. In the case of TES-6h, drug absorption was observed similar to 6 h after administ ration in four of six dogs, but plasma level was low. Further, the loc ation of the dosage forms after oral administration was estimated from the gastric emptying time (GET) and the small intestinal transit time (SITT) using a double marker method. As a result, in vivo performance of TES correlated with the intestinal location. It was concluded that TES-3h would perform well in humans and that the environmental water content in the GI tract affected the in vivo dissolution profile of TE S when the drug release was initiated after entering the colon. (C) 19 98 Elsevier Science B.V.