一个基于卷积的 in vitro-in vivo 对甲基酸延迟释放和延长释放囊的相关性模型
Pawan Kumar Gupta1, Bev Incledon2, Jogarao V S Gobburu1
1University of Maryland, Baltimore, Maryland, USA.
为延长释放甲基酸开发了一种新的体外-体内相关性 (IVIVC) 模型. 该模型通过将体外溶解与体内药物吸收联系起来来支持制造业的变化,用于ADHD治疗.
科学领域:
- 药理动力学 药理动力学
- 药物输送系统 药物输送系统
- 制药科学 制药科学
背景情况:
- 注意缺陷多动症 (ADHD) 通常用甲基化治疗.
- 乔纳伊PM®是一种新型的延迟释放和延长释放囊配方甲基化.
- 批准后的制造变化需要强大的方法来确保药物的性能一致.
研究的目的:
- 为延长释放甲基酸开发A级体外-体内相关性 (IVIVC) 模型.
- 为了确定体外药物溶解和体内药物吸收之间的点对点相关性.
- 为了支持JORNAY PM®的批准后制造变化.
主要方法:
- 利用了三种体外释放配方 (快速,中等,缓慢) 的溶解数据.
- 使用了来自两项体内研究的药理动力学数据.
- 使用基于卷积的方法开发了IVIVC模型,结合了单元冲动响应函数和卷积积分.
- 使用散射图和莱维图分析时间差异.
主要成果:
- 一个A级IVIVC模型成功地开发了延长释放甲基酸.
- 该模型展示了内部可预测性,验证了其预测能力.
- IVIVC模型有效地将体外溶解概况与体内吸收特征联系起来.
结论:
- 开发的IVIVC模型为预测基于体外溶解数据的体内药物性能提供了有价值的工具.
- 该模型可以促进监管提交,并支持延长释放甲基化的制造工艺调整.
- IVIVC方法提高了对药物产品质量和治疗等效性的理解和控制.
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