案例研究:在早期临床前体内研究中,以克雷莫EL为基础的液体配方作为无形固体分散物的简单替代品
Kalle Sigfridsson1, Xiang Zhang2, Antonio Llinas3
1Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, S-431 83 Mölndal, Sweden.
The Journal of pharmacy and pharmacology
|July 24, 2024
概括
配制可溶性较差的晶体化合物A与 (CrEL) 显著提高了其在小鼠中的生物可用性. 这种方法可以指导类似化合物的早期临床前配方开发.
科学领域:
- 药理动力学和药物输送方法
- 临床前制药开发 临床前制药开发
背景情况:
- 难以溶解的晶体化合物对药物输送构成具有挑战.
- 早期识别最佳载体对于有效的药物开发至关重要.
研究的目的:
- 为了增强一种难以溶解的晶体化合物 (化合物A) 的全身暴露.
- 评估各种临床前配方,以改善药物的生物可用性.
主要方法:
- 给小鼠用A化合物 (10毫克/公斤) 加入八种不同的辅溶剂,油和环素混合物.
- 评估了在选定的车辆中添加6%的克里莫 (CrEL) 的影响.
- 测量了包括AUC0-24h和Cmax在内的药理动力学参数.
主要成果:
- 最初的配方导致了低生物利用率 (<18%) 和有限的暴露 (AUC0-24h: 616 μM × h,Cmax: <1.4 μm).
- 添加6%的CREL增加了AUC0-24h和Cmax大约5-10倍.
- 增强CrEL配方的药理动力学特征与无形固体分散 (ASD) 的药理动力学特征相匹配.
结论:
- 对于水溶性较差的化合物,早期对车辆进行查至关重要,以避免在体内进行广泛的测试.
- 无形固体分散 (ASD) 方法更适合后期临床开发.
- 临床前配方,如使用CREL的配方,可以作为发展自闭症的指标.
关键词:
作为一种辅助溶剂,也是一种辅助溶剂.晶体纳米粒子是什么循环德克斯林 (Cyclodextrin) 是一种循环德克斯林.迈塞尔斯 (Micelles) 是一个很好的球员.这些微粒是微粒.纳米晶体是一种纳米晶体.固体分散的固体分散更多相关视频
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