Development of metformin hydrochloride sustained release pellets
This study was performed in order to develop a sustained-release pellet formulation containing metformin hydrochloride (MET), an extremely water-soluble drug, prepared by combination of wax matrices and double layer coatings. The influence of both double layer polymeric coats and wax matrices on the release of MET from sustained-release pellets was investigated. The pellets were prepared by wet-mass extrusion-spheronization methods and then coated with a fluidized bed coater. For the pellets coated with Eudragit NE30D alone, a coating level of nearly 30％ was required to pass the dissolutiontest compared with commercial product, and it was accompanied by an unacceptable lag time. The application of an alcohol-soluble polymeric subcoat, Opadry I, was added before the Eudragit NE30D coating process, which resulted in a marked delay in drug release. However, a faster release was observed for the formulation coated with a high subcoat level 8％) at the end of the dissolution test. A further delay in drug release was observed when a wax matrix, octadecanol, was added to the core pellet formulation. The kinetics of drug release changed from the Higuchi model to a zero order model and the predominant mechanism controlling drug release changed from diffusion to dissolution on increasing the amount of octadecanol within the matrix pellets. In addition, the drug release was markedly influenced by the drug to matrix ratio. In conclusion, the 70％ drug-loaded core pellets with double layer coatings (6％ Opadry I and 9％ Eudragit NE30D) and 20％ octadecanol matrix, produced the desired profile for sustained release compared with the commercial product and these pellets remained stable during storage.
Subcoat Eudragit NE30D Opadry I Wax matrix Sustained-release pellet
Tina T Dong Y
Shenyang E-living Pharmaceutical Co Ltd, Shenyang, China
国际会议
上海
英文
284-293
2007-10-19（万方平台首次上网日期，不代表论文的发表时间）