【作者】 崔哲；

【导师】 崔京浩；

【作者基本信息】 延边大学 ， 药剂学， 2003， 硕士

【摘要】 [目的] 初步确立离心包衣造粒技术制备甲硝唑结肠靶向制剂的方法。[方法]首先，以对乙酰氨基酚为模型药物，淀粉为丸芯材料，50%蔗糖为粘和剂，利用离心包衣造粒法制备淀粉微丸，并以丙烯酸树脂水分散体为包衣材料制备包衣微丸。通过测定微丸粒径大小分布、休止角、脆碎度、水分含量、微丸得率和不同pH条件下的释药特性等优化包衣微丸的制备工艺。其次，以确定微丸制备方法，甲硝唑为模型药物，L-HPC为崩解剂，丙烯酸树脂和乙基纤维素为外层控释包衣材料，邻苯二甲酸二乙酯为增塑剂，滑石粉为润滑剂，来制备控释微丸，用释放度测定法评价微丸在不同pH介质中的释放特性。[结果] 对乙酰氨基酚微丸大小在210?m—1660?m范围的约占88%以上；微丸的休止角为20.06 o，表明流动性良好；微丸的脆碎度为1.11±0.79%, 水分含量为9.05%，一次性微丸得率为51.11%。对乙酰氨基酚包衣微丸在人工胃液和人工肠液的体外溶出实验结果表明，包衣液输送速度小、主机转速快、包衣温度高、包衣液喷浆速度小和喷浆压力大时均可以形成较为均匀的包衣层，使微丸中药物释放速度降低。随着包衣重量增加、乙基纤维素用量增加和崩解剂用量的减少，甲硝唑在人工胃液和人工肠液中的释放呈明显降低的趋势。在Eudragit S100增重25%、增塑剂用量为15%、L-HPC 用量为3%时具有较好的结肠靶向脉冲释放效果。[结论] 离心包衣造粒法可以制备具有结肠靶向特性的甲硝唑微丸，其工艺稳定，批与批之间的重现性良好。更多还原

【Abstract】 [Objective] To establish a preparation technique of Metronidazole- loaded colon specific drug delivery systems by centrifuge coating granulation method. [Method] First, Acetaminophen was preliminary selected as a model drug. Cornstarch, 50% sucrose syrup and aqueous polymethacrylate dispersion were used as core pellet excipient, adhesion reagent and coating solution, respectively. The coating pellets were characterized by size distribution, angle of repose, resistance to abrasion, moisture content and dissolution test in different pH solution. The preparation method of metronidazole-loaded colon specific drug delivery systems (CSDDS) were studied based on the previous work. The effect of low submitted hydroxypropylcellulose (L-HPC), Eudragit S 100 and ethyl cellulose on the dissolution of metronidazole -loaded CSDDS were evaluated in the simulated gastric fluid and simulated intestinal fluid. [Results] More than 88% of Acetaminophen pellets are in the range of 210-1660?m and the angle of repose is 20.06 o. Result of resistance to abrasion test of pellets is 1.11±0.79%, moisture content is 9.05%. The drug release of acetaminophen pellets were have a tendency of decrease while the coating weight, rotary speed of coating pan and coating air pressure increase, but coating speed reduced. The dissolution data of indicated that a higher amount of coating weight and EC in reduced metronidazole release.<WP=6>The metronidazole-loaded pellets showed a kind of dissolution phenomenon similar to pulsed and CSDDS, while formulated with 3% L-HPC as disintegrant and coated by 25% Eudragit S 100 and 15% DEP as Plasticizer. [Conclusion] Metronidazole-loaded CSDDS was successively established by centrifuge coating granulation method with low batch variation and reproducible.更多还原