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立即释放的固体口服剂型的生物豁免专著:Lemborexant

Kristian Beran¹, Bertil Abrahamsson², Naseem Charoo³

¹Fraunhofer Institute for Translational Medicine and Pharmacology, Frankfurt am Main, Germany.

Journal of pharmaceutical sciences

|October 25, 2024

概括

作为双素受体抗剂的伦博雷克桑因生物制药分类系统 (BCS) 的II类限制而面临即时释放剂型的挑战. 经过改进的可开发性分类系统 (rDCS) 通过专注于溶解风险,为虚拟生物等价性评估提供了一条途径.

科学领域:

制药科学制药科学
生物制药生物制药公司
药物开发药物开发

背景情况:

伦博雷克桑是一种双素受体抗剂,被归类为生物制药分类系统 (BCS) 的II类.
这种分类可以防止即时释放 (IR) 固体口服剂型从基于BCS的生物豁免者根据ICH M9指南.
精细的可开发性分类系统 (rDCS) 将lemorexant归类为I类,表明生物制药风险最小.

研究的目的:

探索替代策略,以确定lemborexant配方的生物等价性 (BE).
为了解决基于BCS的方法对lemborexant IR固体口服剂型的局限性.
为lemborexant和类似化合物提出一个虚拟的BE评估途径.

主要方法:

使用精细的可开发性分类系统 (rDCS) 进行lemborexant分类.
进行定制的rDCS调查以确定关键的生物可用性属性.
采用生物相关溶解测试来评估溶解行为.
提出了一条包括rDCS,生物相关溶解,生理基础生物制药建模 (PBBM) 和虚拟BE评估的四步之路.

主要成果:

rDCS分析发现溶解是lemborexant的主要危险因素,而不是溶解性或透性.
人类的临床数据支持说,lemborexant的吸收不受溶解度或透度的限制.
拟议的四步之路提供了一种方法来减轻与配方更改或通用药物引入相关的风险.
这种方法有助于虚拟生物等价性评估,当基于BCS的理由是不可行的.

结论:

改进的可开发性分类系统 (rDCS) 提供了比BCS. lemborexant更细致的风险评估.
溶解是监测lemborexant配方开发和通用替代的关键属性.
将rDCS,生物相关溶解和PBBM结合在一起的虚拟生物等价性评估途径是lemborexant和类似药物的可行策略.
这一战略可以通过减少对临床生物等价性研究的依赖来简化药物开发和仿制药批准过程.

关键词:

吸收方式吸收方式生物制药品分类系统 (BCS) 是一种生物制药品分类系统.没有任何的 Lemborexant.透性透性的精制的可开发性分类系统 (rDCS)可溶性溶解度可溶性溶解度虚拟生物等价性虚拟生物等价性

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