Studies On Tinidazole Colon-Specific Sustained-Release Pellets

In this dissertion, the study was aiming at the preparation of tinidazole （ TNZ ） colon-specific sustained-released pellets and validation in vivo, consisting of preparation methods for pellets, the sustained- release system of coated pellets, stability, Pharmacokinetics. Results show: the colon-specific sustained-release pellets had good appearance and stability; the drug started to release in the colon of beagle dog and the releasing behavior can last over 48 h.UV spectrophotometry was developed for in vitro assay during the studies of release and the content determination in pellets. The plasma concentration in dogs was minitored by using the HPLC ultraviolet method. The preformulation research showed that the drug have a max UV absorption at the 317 nm in the neutral Phosphate buffer solutions, but at the 276 nm in the pH 1.2 HCl aqueous solution. The compatibility of drug and exipients was assessed as well.TNZ colon-specific sustained-released pellets were prepared by means of power layering with the centrifugal granulation equipment made in China. Through the formulation filtration and process observation, it was discovered that the yield of the objective pellets was over 90% and the average TNZ content was about 50%. The results suggested the preparation process and formulation of TNZ pellets can reach the expected goals.Eudragit NE 30D was used for inner coating material and coating process was performed on the centrifugal granulation equipment. The effects of process variables and formulation variables on coating pellets preparation were investigated. The content of PEG-6000 in the optimal inner coating formulation was 20 % , pellets coating weight gain was 10 %. The inner coated pellets showed a sustained-release behavior in pH6.5 phosphate buffer. The description of release profiles suggested that among the different kinetics, the first-order became the most appropriate model to describe release kinetics. The outer pellets coating weight gain is 10 %. With the mimic release tests of high pH and low pH profile, the release from the coated pellets was initiated in the small bowel, and about 60% and 85% of the drug was released to colon region, respectively.Using the instant release tablets on market as the reference, the Pharmacokinetics in beagle dog of TNZ colon-specific sustained-release pellets were studied. The result indicated that T_max was longer, whereas C_max was lower than the instant release tablets on market. From the results we know that the initial drug release of TNZ colon-specific sustained-released pellets started at about 4h. Depending on this lag time, it is obvious that the drug should be released at the small bowel or the colon of the dog. Furthermore, the results showed that the TNZ colon-specific sustained-release had a satisfactory sustained release effect and there were good correlation between absorption percent in vivo and accumulative release in vitro.