Preparatioand In Vitro Evaluation Of Release Properties Of Oxymatrine Colon Targeting Tablets

Objective:The present study was aimed at developing a colonic release system using Oxymatrine as the model drug,preparing Oxymatrine colon-specific tablets combined with pH dependence, flora trigger type and time dependent triple principles.The new system can deliver drugs to colon specificly,enhance colon local concentrantion and local bioavailability, improve therapeutic effect and reduce side effects of drugs. the formulation and preparation craft, the medicine release mechanism, the medicine release affected factors, the medicine release stability of this system has been researched.Methods:The release degree in vitro was considered as evalution indicator, the test of the influence factors were used to screen the prescriptions of tablets. The preparation parameters of coating were investigated by evaluation of the film coating thickness and uniformity. The multi-layered coating including isolation layer, time-lag layer , flora trigger layer and enteric layer were prepaered. The initial screening of coating materials were investigated by a large number of trial tests, the prescription composition and coating thickness were invertigated through all levels of single-factor study and orthogonal design, and the release in vitro study was uesd to test and verify the best formulation. The content of Oxymatrine colon-specific enteric tablets was determined by high performance liquid chromatography,and the release property of Oxymatrine colon-specific enteric tablets was determined by rotating basket method in different dissolution environment. The initial stability of Oxymatrine colon-specific enteric tablets was investigated .Results: The preparation fomula of core tablets is 300g Oxymatrine, 200g microcrystalline cellulose, 250g PVPP, adequate PVP alcohol solution as adhesive and 3.8g magnesium. The coating tablets preparation fomula: the prescription composition of isolation layer is HPMC and PEG6000; time-lag layer is 37.5 g Eudragit RS 30D, 12.5 g Eudragit RL 30D ,3 g methylparaben,135 mL water; flora trigger layer is 37.5 g Eudragit RS 30D, 12.5 g EudragitRL 30D ,100 mL 1.5% chitosan solution,3 g methylparaben,60 mL water ;enteric layer is EudragitL100-55. The coating weight gain of four layer are 2.0%, 6.0%, 5.0% and 3.0%. Oxymatrine colon-specific enteric tablets has no dissolution in 2-4 hours in hydrochloric acid solution,6 hours in pH6.8 phosphate buffer.But in pH4.0,pH5.0,pH6.0 and pH7.4 phosphate buffer,the accumulation release could reach over 50% in 8 hours. The result of stability test showed that the Oxymatrine colon-specific enteric tablets was stable under strong light condition , high humidity and high tempeartuer.Conclusion: The best prescription and preparation technology of Oxymatrine colon-specific enteric tablets are reasonable, simple, effective, repeatable, can meet with demand of preparation. The quality standard of Oxymatrine colon-specific enteric tablets is initially established and the methods have good sensitiveness, accurance and reproducibility. The results of stability study shows that the quality of Oxymatrine colon-specific enteric tablets is stable.