Scintigraphic evaluation of a novel colon-targeted delivery system (CODES) in healthy volunteers.

The purposes of this study are to investigate the gastrointestinal transit and release properties of a novel, colon-targeted delivery system (CODES) administered to healthy volunteers using gamma scintigraphy and to confirm that lactulose functions to promote disintegration in the colon. Two placebo formulations were studied: one was CODES, which consisted of a lactulose containing core overcoated with both Eudragit E and Eudragit L designed to rapidly disintegrate in the colon, the other was lactulose-free reference formulation (LFRF) that consisted of lactulose-free tablet core overcoated with the same materials. Transit and disintegration of the radiolabeled formulations were followed by gamma scintigraphy. In the fasted state, scintigraphic images indicated that CODES started to disintegrate in the ascending colon in the majority of subjects at 7.11 +/- 2.01 h post-dose. Disintegration was complete within 1 h following commencement of in vivo release. In contrast, LFRF presented with prolonged in vivo disintegration properties. In the fed state, the disintegration period of CODES was almost comparable to that observed in the fasted state. Gamma scintigraphic studies clearly showed that CODES provides for rapid target site release in the colon regardless of the ingestion of food.

Studies on lactulose formulations for colon-specific drug delivery.

A novel, colon-targeted delivery system (CODES), which uses lactulose, was investigated in this study. Lactulose is not absorbed in the upper GI tract, but degraded to organic acids by enterobacteria in the lower gastrointestinal tract, especially the colon. A CODES consists of three components: a core containing lactulose and the drug, an inner acid-soluble material layer, and an outer layer of an enterosoluble material. When a CODES containing a pigment was introduced into the rat cecum directly after shaking in JP 2nd fluid for 3 h, pigment release was observed 1 h after introduction. A CODES containing 5-aminosalicylic acid (5-ASA) was orally administered to fasting and fed dogs to evaluate its pharmacokinetic profiles. 5-ASA was first detected in plasma after 3 h, which is the reported colon arrival time for indigestible solids, after dosing to fasting dogs. The T(max) in fed dogs was delayed by 9 h when compared to fasting dogs. This corresponds to the gastric emptying time. However, the C(max) and AUC under fed conditions were almost as same as those under fasting conditions. The results of this study show that lactulose can act as a trigger for drug release in the colon, utilizing the action of enterobacteria.