Metronidazole Colon Sustained Release Pellets

Metronidazole has been widely used to treat trichomoniasic and amoeba and various kinds of anaerobic infection. Recently, Metronidazole was reported as a potential drug for the treatment of colonitis. But there is not a colon- specific dosage form on the market now. Oral administration of conventional tablet of metronidazole was absorbed in intestine mostly and it was hard to get to be available at colon, therefore its effect for colonitis was not satisfactory. Rectal administration of metronidazole could increase drug concentration in colon but the inconvenience of this type of administration might limit its use. Intestine perfusion was also applied but resulted in less compliance. The purpose of the present study was to design a kind of oral administrated colon-specific dosage form prepared by centrifuge granulation technology. The colon-specific administration could release in colon with high concentration and without absorption in small intestine. And with the same clinical relevant dose, colon-specific administration could have greater effect, and reduce adverse drug reactions.Metronidazole was identified according to positive identification reaction, and an absorption peak at 278 nm and 320 nm by ultraviolet scanning pattern in different medium. Additionally, the equilibrium solubility and stability of metronidazole in water and different pH buffer was investigated.Study on the absorption of metronidazole in rats, intestine indicated it was absorbed at whole intestine by followed first-order kinetics.On the base of characteristic ultraviolet absorption of metronidazole, the ultraviolet spectrophotometry (UV) and reverse-phase high performance liquid chromatography (RP-HPLC) methods were developed to determine the metronidazole content. The linearity, specificity, repeatability and recovery met with the requirements of Chinese Pharmacopoeia (edition 2005). Metronidazole pellets was prepared by centrifuge granulation technology with microcrystalline cellulose as matrix and 3% HPMC solution as adhesive agent. The powdery property of the pellets was investigated and the quality of the pellets core was assessed. Eudragit?NE30D aqueous dispersion was used as inner layer time-controlled coating material, Eudragit?FS30D aqueous dispersion was used as outer layer pH- controlled coating material to prepared a pH and time controlled colon-specific delivery system of metronidazole. Drug accumulated release percentage was used to evaluate the prescription and preparation conditions. The results suggested the coated pellets exhibited a marked lag time and followed the Higuchi function.Followed Chinese Pharmacopoeia (edition 2005), the stability of the colon-specific capsules was investigated, which included influence factors and acceleration test. The appearance of pellets, release and drug content were major items investigated under the conditions of strong...