Research And Perparation Metformin Hydrochloride Sustained Release Tablet With Carbopol(?) Polymer As Matrix Excipient

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.To reduce the side effects and maintain relatively constant plasma concentration, a sustained released tablet of once daily administration was designed and prepared using Carbopol (?) polymer as basic matrix material and combining with other excipients.High-performance liquid chromatography (HPLC) method with UV detection was developed for the content of metformin hydrochloride and the content of sustained release tablets. Ultraviolet (UV) specrophotomatry method was developed for determination of drug release. The pharmacokinetics of metformin hydrochloride matrix sustained release tablets in vivo were detected by high-performance liquid chromatography (HPLC) method with UV. These methods are simple, rapid and reliable.In preformulation studies, physical and chemical properties of metformin hydrochloride such as stability of aqueous solution and stability in different influencing factors were investigated. On this basis of preformulation studies, the factors affecting the drug release behavior were assessed by single-factor tests. The factors affecting the drug release behaviors from metformin hydrochloride matrix sustained released tablets included type of retardant, using level of Carbopol polymers, pressure, diluent, adhesives and preparation process factors. Then orthogonal design method was used for formulations optimization to selecte the optimal formulation. The results of evaluation in vitro show that:the weight difference, hardness, brittle broken degrees and release rate can meet the standards. The preliminary stability tests showed that the sustained release tablets are relatively stable in high light, high temperatature and high humidity conditions. And the content and release rate of the tablets were not significantly change. In the accordance with the condition of manufacturer, the process of small samples (2000 tablets) and pilot-plant test scales were designed.The way of metformin hydrochloride from matrix sustained release tablets could be described as the mutual result of drug diffusion and matrix erosion.The studies of pharmacokinetics of metformin hydrochloride matrix sustained release tablets in rabbits verified that the bioequivalence of metformin hydrochloride matrix sustained release tablets were 98.97% relative to congeneric product abroad. The release of metformin hydrochloride in vitro is correlative with the absorption fraction in vivo.