Study On Compound Metformin Hydrochloride Sustained-Release Pellets

In this thesis, Metformin Hydrochloride pellets were prepared by extrusion-spheronisation. Compound sustained-release pellets of Metformin Hydrochloride and Glibenclamide were prepared by coating with sustained-release and normal coating materials. The preparation methods for pellets and influence factors involved, stability, pharmacokinetics and bioavailability on pellets were studied completely and thoroughly. Results show: the compound sustained-release pellets had good appearance and stability, the sustained-release property of pellets was marked.Ultraviolet spetrophotometry method was developed for assaying content and drug release of Metformin Hydrochloride. The method was monitored by methodology and was simple, accurate to be used in vitro. High performance liquid chromatography method was developed to determine content, content uniformity and dissolution of Glibenclamide.The formulation and technology of Metformin Hydrochloride prompt-release pellets were optimized with orthogonal experiment design. Aqueous disperdion (Eudragit?NE30D) was used as coating material and coating process was performed on a mini-fluidized bed spary coater. The effects of process varibles and formulation varibles on pellets preparation were investigated. The formulation and technology of Metformin Hydrochloride sustained-release pellets were optimized. Results show: the coated pellets had a marked sustained-release property, the drug release profile in vitro followed first order kinetics.The Metformin Hydrochloride sustained-release pellets were further coated to prepare compound sustained-release pellets with normal coating materialwhich contained Glibenclamide. The formulation and technology were optimized. Dissolution and content uniformity of Glibenclamide were also invetigated. Results show: Glibenclamide could dissolute completely within 45 min in vitro and content uniformity of it was ideal. Further test indicated that outer coating had no influence on the release behaviour of Metformin Hydrochloride.The fit factors method was used in this thesis to study the stability of compound sustained-release capsule. The drug content and release stability of the capsule were both good under high temperature, high humidity and intensive light tests. Pharmacokinetics and bioavailability studies of compound sustained-release capsule and Metformin Hydrochloride prompt-release capsule in dogs were performed based on determination of plasma concentration of drugs at different intervals after a single oral administration. Tmax of compound sustained-release capsule was 3.98 hours and that of prompt-release capsule was 1.94 hours. The relative bioavailability of Metformin Hydrochloride was 96.27% compared with prompt-release capsule. Obvious correlation existed between absorption fraction in vivo and the release percentage in vitro.