Study On Bacterially Triggered Colon-Specific Preperation Of Hydrocortisone

Background and Purpose: Oral colon-specific drug delivery system(OCDDS) is a system through which the oral drug will not release in the upper gastrointestinal tract but disintegrate and release in the colon and play local or systemic treatment in the colon. At present, there are several kinds of OCDDS: pH-dependent, time-delay, pressure-controlled and bacterially triggered colon-specific drug delivery system. In the past, the researches of OCDDS were focused on pH-sensitive and time-delay delivery system. However, the problem is that the drug can not be delivered and release in the targeted colon exactly, due to large individual variation. Therefore, bacterially triggered colon-specific drug delivery system (BCDDS) gets more attention. BCDDS is based on a lot of bacteria that can produceβ-glucuronidase,β-glucosidase, cellulose, nitro-reductase, azoreductase et al. Many polymer materials are degraded by the enzymes which only exist in the colon. Chitosan is a kind of nontoxic and good biocompatible polysaccharide whose glycosidic bond can be degraded by colon-specific enzymes. Moreover, chitosan exhibit some activities of antiphlogosis and hemostasis. So it can be used as a good colon targeting carrier.The subject is aim to prepare a kind of colon-specific bilayer-coated tablets which specially deliver drug to colon.Methods: Hydrocortisone plain tablets was prepared and coated with chitosan as inner layer and ACRYL-EZE as outer layer. Single-factor analysis was carried out to find out the main factors affecting the drug release in the process of coating chitosan.Then orthogonal experiment design was carried out to find out the best prescription. Then study the colon targeting of bilayer-coated tablets in vitro. In vivo, pharmacokinetics of colon targeted tablets was carried out using Hydrocortisone ordinary and enteric tablets as reference. Then dissect dogs to investigate the delivery of the tablets in gastrointestinal tract.Results: A2B2C3 is selected as the best prescription through orthogonal experiment and weight of coating is the major factor influencing the release. The results of drug release in vitro showed that both colon targeted tablets and enteric tabletse almost did not release (<1%) in simulated gastric juice. And enteric tablets almost completely release ( >95%) and colon targeted tablets release less than 10% in simulated small intestine juice. The drug release of colon targeted tablets increased markedly in simulated colonic fluid after 14 hours. Pharmacokinetics results showed that Tmax of ordinary tablets is 1.04h, Tmax of enteric tablets is 2.42h, Tmax of colon targeted tablets is 9.83 h .Animal anatomy experiments showed that the tablets remained intact in the stomach and did not disintegrate in the small intestine but disintegrated in the colon.Conclusion: Chitosan bilayer-coated tablets can be used as good carrier for colon specific drug delivery system.