葛根素复合骨架缓释片剂的研究.pdf

PUE复合骨架缓释肆裁的研究摘要本文以天然多糖类高分子聚合物甲壳胺(CS)与海藻酸钠(AL)为三|三要辅料,秘用二者在体内条件下的相互作用,形成聚电解质复合物,作为复合骨架,制备葛报素(PUE)缓释片。,首先,研究了CS与AL在模拟体内条件下的相互作用,通过特性粘数法,IR光谱,。并对影响因素进行了考察。~,CS与AL的反应质量比恒定,、随着CS的脱乙酰度的降低,反应质量比(CS:AL)增加。以微溶于水的葛根索为模型药物,通过DTA法对药物与主要辅料的相互作用进行了研究。/ 测定了葛根素的溶解度,并考察了不同pH条件对溶解度的影响。? 对影响葛根素缓释片释放度的因素进行考察,结果表明,不 I司脱乙酰度的CS及用量与AL的粘度对释放度影响明显;CS的密度及AL的粒度对释放度有影响;CS的粘度与AL的用量对释放度的影响较小。制备工艺考察表明,制软材时,润湿剂影响二F颗粒n≈一些性质,间接影响片重差异:片剂的硬度对释放度影响明疆。/葛根索缓释片处方优化采用正交没计。释放度测定结果表 I帅,、药物的释放数据以tliguehi方程拟合比较接近实测结采,但残差分析表明,与Higuchi方程拟合相比,以非线性方程拟合能更好地预测体外的释放情况。释放度测定采用篮法与桨法没有明显差异;不同转速在释放初期(1~2小时)对释放度有影响;不同pH值的释放介质对释放速率有明显影响。通过对三批样品释放度的测定,结果表明,葛根索缓释片释放稳定,重现性良好。文中考察了高温,高湿,光照条件对缓释片的影响,并测定7r PUE复合骨架缓释片弃i的研究 f了加速试验,室温留样观察一年的样品。试验结果表明,缓释片在光照(3000Lax)条件下,硬度J{!|加,释放度有些变化;高温(80 ℃)条件下,释放速率明显增加:在高湿(%)条件下,片面变化大。吸潮严重:在三个月加速试验及室温留样试验条件下稳定。建议缓释片在密封、低温和避光条件下贮藏。家犬体内生物利用度研究表明,%,达峰时间延长为4,0小时,,,血药浓度相对平稳。体内外相关性良好。矿关键词: ABSTRACT The harides such as chiston(CS)and SOdium alginate《AL)were used as the primary excipients of )was selected as the model polyelectroly,plex of CS-AL which was formed ingastrointestinal pH circumstances was regarded as the skeleton matrix of sustained release tablet interaction between CS and AL was studied by specific viscosity method,IR spectrum and plex was demonstrated to OCCUr by electrostatic polymerization between acationic(CS)and an anionic(AL) mixing ratio of CS and AL was proved to be stable inmediafrom 37 P by determinating the specific viscosity of supernatant solution of CS-AL the .%(degreeof deacetylatio川of CS decreased,the mixing ratio increased. The mutual action was studied by DTA between PUE and theprimary solubility ofPVE was measured and was stable ~. Factors influencing release profiles of sustained release tablets of PUE Were inv