多索茶碱脉冲控释微丸的研制

Preparation of Doxofylline Pulsatile Controlled-release Pellets

关键词:  多索茶碱  脉冲释药微丸  溶胀层  控释层

Key words:  doxofylline  pulsatile controlled-release pellets  swelling agent  controlled-release membrane

摘要:

目的 研究多索茶碱脉冲控释微丸的制备工艺，并考察其释药性能。方法 以微晶纤维素为骨架材料采用挤出滚圆法制备载药丸芯，通过流化床包衣法分别覆上交联羧甲基纤维素钠作为溶胀层、乙基纤维素和羟丙甲纤维素作为控释层制备多索茶碱脉冲微丸，通过单因素考察筛选丸芯、溶胀层、控释层的处方组成对体外释药性能的影响。结果 以微晶纤维素、羧甲基淀粉钠和乳糖为添加剂可制得性能良好的高载药微丸。随着溶胀层厚度的增加，药物释放时滞变短，速率显著增加；随着控释层包衣厚度的增加，时滞延长，释药减慢；控释层中羟丙甲纤维素用量或分子量增加，时滞缩短；控释层中增塑剂用量增加，时滞延长。结论 所得包衣微丸具有良好的脉冲释药性能，有广阔的应用前景。

Abstract:

OBJECTIVE To develop a preparation of pulsatile controlled-release pellets for doxofylline. METHODS The pellet cores containing doxofylline were prepared by extrude-spheronization method. Then the pellets were coated by croscarmellose sodium as swelling layer and the mixture of ethyl cellulose and hydroxypropyl methyl cellulose as controlled release layer via fluidized bed coating method. The effects of pellet cores, swelling layer and controlled release membrane on the profile of drug release in vitro were investigated by single factor test. RESULTS The high doxofylline-loading pellet cores with satisfactory characters were obtained by employing microcelluose, sodium carboxymethyl starch and lactose as ingredients. When the thickness of the swelling layer increased, the lag time of drug release was prolonged and the release rate was enhanced. With the HPMC quantity or molecular weight increasing, the lag time was reduced. The lag time could also be prolonged by plasticizer. CONCLUSION The obtained pellets display good pulsatile drug release behavior, which had a great potential for application.