建立生物预测溶解和生物等价安全空间,使用生理学基础的生物制药模型为塔克罗利斯延长释放囊
Fulin Bi1, Tong Yuan1, Baohong Zhang2
1Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China.
AAPS PharmSciTech
|December 17, 2024
概括
开发精确的体外溶解方法对于通用tacrolimus延长释放 (ER) 囊至关重要,这些囊具有狭窄的治疗指数 (NTI). 基于生理学的生物制药建模 (PBBM) 和生物相关媒体可以预测生物等价性 (BE) 并为NTI药物建立安全空间.
科学领域:
- 制药科学 制药科学
- 药物开发 药物开发
- 生物制药生物制药公司
背景情况:
- 延长释放 (ER) 囊具有狭窄的治疗指数 (NTI),使它们对体内暴露的变化敏感.
- 对于仿制药来说,更严格的生物等价性 (BE) 标准需要对药物释放动力学的精确评估.
- 具有高的体内预测能力的体外溶解方法对于通用NTI药物开发至关重要.
研究的目的:
- 开发和验证基于生理学的生物制药建模 (PBBM) 方法,用于5毫克塔克罗利斯ER囊.
- 建立生物预测溶解方法,使用流通细胞装置 (USP IV) 和生物相关介质.
- 通过PBBM和虚拟生物等价性试验,为塔克罗利斯ER囊提出生物等价性 (BE) 安全空间.
主要方法:
- 基于生理学的生物制药建模 (PBBM) 已被开发和验证为tacrolimus ER囊.
- 使用具有生物相关介质的流通细胞装置 (USP IV) 用于评估参考和非BE测试配方.
- 虚拟生物等价性试验使用PBBM进行,以定义BE安全空间.
主要成果:
- 一种生物预测溶解方法已经成功地为塔克罗利斯ER囊建立.
- 通过PBBM,可以识别可能通过内部质量控制但未能达到生物等价性的配方.
- 该研究提出了定义NTI药物生物等价 (BE) 安全空间的标准.
结论:
- 基于生物相关溶解的生物预测溶解方法为仿制药开发提供了显著的优势.
- 将 PBBM 与生物预测性溶解方法相结合,为NTI药物的生物等价性评估提供了一种实用的方法.
- 这种综合方法是开发新型塔克罗利斯ER配方的宝贵工具.
相关概念视频
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