Preparation for Colon-specific Pellets Controlled by Enzyme Triggering Osmotic Pump and Its Investigation of the Release in Vitro

OBJECTIVE To prepare colon-specific pellets controlled by enzyme triggering osmotic pump with coating materials of calcium pectate and cellulose acetate, and with 5-amino salicylic acid(5-ASA) as a model drug, as well as to investigate the characteristics and mechanisms of drug delivery in vitro. METHODS Pan coating was adopted to prepare medicine containing pellets. L₉(3)⁴ orthogonal design was applied to optimize the formulation of coating solution and dosage of penetrant in pellets with evaluation index of release in vitro, while mathematical models of the in vitro drug release was fitted. RESULTS　The optimum process parameters preparing for 5-ASA colon-specific pellets controlled by enzyme triggering osmotic pump was as follows: coating weight gain was 25%, the dosage ratio of 5-ASA to NaCl in pellets was 3∶1, the dosage ratio of cellulose acetate to calcium pectate in coating solution was 2∶3. The cumulative release rate of prepared pellets was lower than 8% in simulated gastric fluid (2 h) and in simulated intestinal fluid (4 h) while over 70% in simulated colonic fluid(12 h). All this showed that the pellets possessed excellent colon-specific performance and maintained local drug concentrations by a sustained release in colon. A further study on the release mechanism demonstrated that the in vitro drug release performance belonged to zero-order release. CONCLUSION Colon-specific pellets controlled by enzyme triggering osmotic pump with coating materials of calcium pectate and cellulose acetate have the function of colon-targeting.