Preparation and evaluation of colon adhesive pellets of 5-aminosalicylic acid.

Oral modified-release delivery systems, such as bio-adhesive one, enable drug delivery to affected regions and minimize the side effects by reducing the systemic absorption. Our aim was to develop colon adhesive pellets of 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis. The core of the pellet was formulated from bioadhesive agents, Carbomer 940 and hydroxypropyl cellulose (HPC), by extrusion/spheronization method and coated with Surelease(®) as inner layer for waterproof and with Eudragit(®) S100 as outer layer for pH control. The rat model of ulcerative colitis was used to evaluate the efficiency of our loaded pellets as a drug carrier. Microcrystalline cellulose 101 (PH 301) was found to be the best agent for pellet core. The ratio of CP940 to HPC should be kept as (1:1) to achieve high bioadhesion. When the amount of Surelease(®) was from 16% to 20% and of Eudragit(®) S100 was 28%, the dissolution profiles of coated pellets revealed no drug release in the artificial gastric fluid (pH 1.0) within 2h and less than 10% was released in phosphate buffer (pH 6.0) within 2h whereas complete dissolution was observed in colonic fluid of pH 7.4 for 20 h. The animal experiment showed that 5-ASA loaded colon adhesive pellets had optimal therapeutic effect. We showed a novel approach to prepare effective bioadhesive pellets as colon targeted drug delivery system.