Oral Colon-specific Delivery System Research Articles

Preparation and in vitro evaluation of macrocyclic metronidazole conjugates as an oral colon-specific delivery system

The antimicrobial drug metronidazole (MTZ) was covalently conjugated to the secondary hydroxyl groups of β-cyclodextrin through ester linkage using sodium hydride as the deproton reagent. The preliminary release behavior of MTZ in rat gastrointestinal tract contents was studied at 37 °C within 24 h. In the contents of stomach, the conjugates did hardly release MTZ, released MTZ only 9.5 % in the contents of small intestine, and released MTZ significantly up to 43.6 and 40.2 % in the contents of cecum and colon, respectively. These results indicate that the conjugate activation took place site-specifically in the rat cecal and colonic contents, probably via the biodegradation by glycosidases and hydrolases. The present MTZ-appended cyclodextrin conjugate may be of value as an orally administered delayed-release and/or colon-specific prodrug.

Konjac glucomannan and xanthan gum as compression coat for colonic drug delivery: experimental and theoretical evaluations

Compression coated tablets for oral colon specific delivery systems were developed with a mixture polysaccharide of konjac glucomannan (KGM) and xanthan gum (XG) as the compression coat. Diffusion of cimetidine from compression coated tablets was investigated by release experiment in Vitro. 0.22U/mL β-mannanase was applied in the mimic colon solution. The structure of the mixture polysaccharide was studied by an atomic force microscope (AFM). The experimental results indicate that a KGM70 tablet with a 0.4 g coat is of good design, due to a less than 5% drug loss in the mimic upper gastrointestinal solution by the synergistic interaction between XG and KGM, and due to about 50% cumulative release in the mimic colon solution by degradation after 24 hours. The release mechanism and model are discussed based on different periods of drug release including the delay of the drug, the constant release without an enzyme and the delay of degradation. Under hydrolysis by β-mannanase, drug release from the tablet with KGM coat shows an exponential increase, while that from the dosage with the mixture polysaccharide coat is an approximately zero-order process in which the constant release rate relates to the release velocity of a non-degraded system, the content of KGM within the coat and the average molecular weight ratio of KGM to XG. It was found that XG was the framework of the polysaccharide mixtures by AFM, which is similar to the analysis results from experiments on drug release.