摘要: 目的 建立双波长紫外分光光度法测定左乙拉西坦生物黏附缓释片体外释放度的方法，优化筛选左乙拉西坦生物黏附缓释片处方。方法 本文以体外释放度为指标考察了HPMC的黏度、卡波姆的黏度以及不同黏合剂对左乙拉西坦缓释片释放度的影响，确定了缓释片处方。采用星点设计-效应面法对其处方进行优化筛选，HPMC用量(X1)和Carpol用量(X2)作为考察目标。测定不同处方的体外释放度，选出最佳处方。结果 建立了紫外分光光度法用于体外释放度的测定。LEV在0.10 ~ 0.60 mg/mL浓度范围内，A = 0.7269 C + 0.0003(r = 0.9996)，本方法准确、重现性好、符合方法学要求。确定了体外黏附力的测定方法，并成功筛选出最优处方。结论 采用星点设计-效应面法得到了左乙拉西坦生物黏附缓释片的处方优化模型，实现了处方优化，可以作进一步的研究。4883
关键词：左乙拉西坦；生物黏附缓释片；星点设计-效应面法；释放度
Study on the Formulation Optimization of Levetiracetam Bioadhesive Sustained-Release Tablets by Central Composite Design-Response Surface Methodology
Abstract: Objective To screen the optimizing prescription of bioadhesive sustained-release tablets of levetiracetam，establish the assay method for the release in vitro of levetiracetam. Method In this paper, the release rate in vitro was used as indicator to evaluate the effects of HPMC viscosity, Carpol viscosity, cohesives on the bioadhesive sustained-release tablets of levetiracetam. To determine the sustained-release tablets prescription. The prescription of was excellently screened by central composite design-response surface methodology, and the dosage of HPLC(X1) and Carbomer(X2) as the research factors. The release rate in vitro of each prescription was determined and analyzed so as to choose the best. Results UV method was developed to determine the releasing degree in vitro. The concentration of Levetiracetam over the range of 0.10~0.80 mg/mL, A = 0.7269 C + 0.0003(r = 0.9996)，which showed this method was accurate, reliable and reproducible. Determine the method for measuring adhesion in vitro and screening the optimal prescription. Conclusion The established model based on the theory of central composite design is suitable for screening the optimizing prescription of bioadhesive sustained-release tablets of levetiracetam, and it can be used for further research.
Keywords: levetiracetam; bioadhesive sustained-release tablets; central composite design-response surface methodology; release rat
目 录
1 绪论 1
1.1 生物黏附制剂研究进展 1
1.1.1 生物黏附机制 1
1.1.2 常用的生物黏附材料 2
1.1.3 生物黏附新剂型的开发 2
1.1.4 生物黏附性能测定 2
1.1.5 展望 3
1.2 左乙拉西坦研究综述 3
1.2.1 研究背景 3
1.2.2 研究进展 4
1.2.3 药效学研究 5
1.2.4 药理作用 6
1.2.5 临床研究 6
1.2.6 不良反应 6
1.3 课题立项意义 7
1.4 课题研究内容 7
2 左乙拉西坦生物黏附缓释片处方前研究 8
2.1 材料 8
2.1.1 仪器 8
2.1.2 试药 8
2.1.3 动物 8
2.2 体外释放度测定方法学研究 8
2.2.1 紫外吸收波长的选择 8 星点设计效应面法优选左乙拉西坦生物黏附缓释片的处方研究:http://www.751com.cn/yixue/lunwen_1690.html