In vivo evaluation of a novel pH- and time-based multiunit colonic drug delivery system

Background: Targeted drug delivery to the colon is important for topical treatment of inflammatory bowel diseases. Established targeting systems predominantly focus on either pH- or time-dependent release, or bacterial degradation. Aim: To perform a three-phase, crossover design trial evaluating a novel combined pH- and time-based multiunit delivery system. Methods: Twelve healthy male volunteers each received 200 mg of caffeine as either uncoated immediate release tablets, coated pellets with pH-dependent rapid release (EUDRAGIT FS 30D), and pellets with pH- and time-based release (inner layer EUDRAGIT RL/RS 30D; outer layer EUDRAGIT FS 30D). Orocecal transit time was measured using lactose-[C-13]ureide. Serum concentrations of caffeine were measured by high-performance liquid chromatography. Results: In contrast to the uncoated tablet, both coated systems reached the ileocecal region almost at the same time (3.19 +/- 0.71 and 3.33 +/- 0.81 h). Serum caffeine profiles were significantly prolonged for the pH and time delivery system compared with the pH-only based system (median t(max) 12.0 vs. 5.5 h; P < 0.001). This was further reflected by a lower C-max value and a lower area under the curve within 24 h after application. Conclusion: Compared with the conventional delivery systems, drug release from the new dosage form may offer a new dimension for the oral treatment of mid to distal ulcerative colitis.