在体外-体内关系和微观结构的洞察长期作用的levonorgestrel子宫内系统
Suraj Fanse1, Andrew Clark2, Quanying Bao1
1University of Connecticut, School of Pharmacy, Storrs, CT 06269, USA.
概括
通用levonorgestrel子宫内系统 (LNG-IUSs) 由于复杂的配方和长效释放而面临发展障碍. 这项研究确定了LNG-IUS的体外-体内相关性 (IVIVR),有助于仿制药的开发和可访问性.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 材料科学 材料科学 材料科学
背景情况:
- 莱沃诺格斯特勒子宫内系统 (LNG-IUSs) 是非常有效的避孕药,但在美国没有通用版本.
- 挑战包括由于复杂的配方和超长时间 (长达8年) 的药物释放,与参考药物实现生物等价性 (Q1/Q2相似性).
- 通过长期释放测试和影响生物利用性的微观结构变异,证明生物等价性受到阻碍.
研究的目的:
- 对商业LNG-IUS (Mirena®,Liletta®) 进行全面的逆向工程分析.
- 为LNG-IUSs开发一种加速体外释放方法.
- 为了建立一个体外-体内关系 (IVIVR) 的超长效应的IUSs.
主要方法:
- 使用FTIR,ssNMR,DSC,TGA,SEM-EDX,XRM和FIB-SEM的商业液化天然气IUS的逆向工程与AI分析.
- 实时体外释放测试 (长达7年) 和加速释放方法 (100天) 的开发.
- 释放后分析levonorgestrel分布,颗粒大小,多孔性和结构变化.
主要成果:
- 商业LNG-IUS的聚合物交叉连接,物理化学和机械性能的表征.
- 识别影响释放动力学和微观结构变化的组成差异.
- 首次报告了超长效应的静脉注射器的体外-体内关系 (IVIVR),将体外释放与人体体内数据相关联.
结论:
- 已建立的IVIVR为评估LNG-IUS药物释放提供了预测工具,可能加速开发.
- 这项研究为制造商提供了一份路线图,以优化通用LNG-IUS的配方和制造流程.
- 预计这些发现将提高公众获得有效的长效可逆避孕药的机会.
相关概念视频
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