Time- and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-aminosalicylic acid.

Abstract

To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively. DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit L100 and S100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied. Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium, but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets, 5-ASA release was significantly governed by pH. Moreover, the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release. Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.