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

Abstract

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. To perform a three-phase, crossover design trial evaluating a novel combined pH- and time-based multiunit delivery system. 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-[13C]ureide. Serum concentrations of caffeine were measured by high-performance liquid chromatography. 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 tmax 12.0 vs. 5.5 h; P < 0.001). This was further reflected by a lower Cmax value and a lower area under the curve within 24 h after application. 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.