Maleate Trimebutine Sustained-release Capsules

Trimebutine maleate has been widely used as a spasmolytic drug to treat functional digestive disorders and irritable bowel syndrome (IBS). Its biological half-life is relatively short (about 2.7 hours), therefore it was normally adiministed in shorter intervals, and that may result in bigger the fluctuation of plasma concentration, some adverse drug reactions, and also less compliance . The purpose of the present study was to design a kind of trimebutine maleate sustained-release pellet capsule which would reduce dosing frequency and be more convenient for patients. The material tested was identified as trimebutine maleate according to positive identification reactions, and an absorption peak at 267 nm by ultraviolet scanning pattern. Additionaly, the equilibrium solubility and stability of trimebutine maleate in water and different pH buffer was investigated. On the base of characteristic ultraviolet absorption of trimebutine maleate, the ultraviolet spectrophotometry (UV) and reverse-phase high performance liquid chromatography (RP-HPLC) methods were developed to determine the trimebutine maleate content and for some relevant impurities in pellets. The linearity, specificity, repeatability and recovery met with the requirements of Chinese Pharmacopoeia (edition 2000). Trimebutine maleate 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 determined. Eudragit?NE30D aqueous dispersion was used as coating material. Drug accumulated release amount was used to evaluate the formulation and preparation conditions. The release of trimebutine maleate from pellets were studied with different media, different equipments and different speeds of revolution. The release profiles suggested the coated pellets exhibited a marked sustained-release property and followed the first-order release kinetics. Followed Chinese Pharmacopoeia, the stability of the preparation were investigated, which included influence factors and acceleration test. Under the strong light, high temperature, high humidity condition, appearance of pellets, specific identification reactions, release and content determination were detected for the stability studies. The results showed that the coating membrane of pellets was sensitive to temperature and humidity, but stable for strong light. Therefore the preparations should be preserved at cool and hermetic condition.