从表面活性剂制剂中口服吸收:分子溶解药物对生物可用性的影响
Florentin Lukas Holzem1, Neil Parrott2, Jeannine Petrig Schaffland2
1Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark; Pharmaceutical R&D, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
Journal of pharmaceutical sciences
|July 26, 2024
概括
这项研究表明,只有难溶药物的分子溶解分量,而不是合物相关药物,驱动口服吸收. 准确的药理动力学建模依赖于这种自由药物度来进行可靠的预测.
科学领域:
- 制药科学 制药科学
- 药物输送和配方 药物输送和配方
- 生物制药生物制药公司
背景情况:
- 难以溶解的化合物的口服药物吸收通常受制于增加表面溶解度的配方策略.
- 虽然配方增强了药物的整体溶解,但只有分子溶解 (自由) 分数容易被吸收.
- 与体相关的药物分离物可能不会对全身暴露有显著的贡献.
研究的目的:
- 为了比较分子溶解与明显溶解药物度对Alectinib口服吸收的影响.
- 评估基于生理学的生物制药模型 (PBBM) 的预测性能,使用不同的药物溶解指标.
- 为了建立一个改进的体外-体内相关性 (IVIVC) 难溶性药物配方.
主要方法:
- 准备了Alectinib配方,其中酸 (SLS) 的度各不相同.
- 溶解试验是在模拟食和禁食状态条件下进行的.
- 用微透析测量分子溶解药物,使用离心/过测量明显溶解药物.
- 为了构建IVIVC和PBBM,使用了体外数据,将预测与人类的药理动力学数据进行比较.
主要成果:
- 增加SLS含量线性增加了模拟肠液中明显溶解的阿列克提尼布.
- 然而,分子溶解药物度与SLS含量仅略有差异.
- 使用明显溶解的药物的 PBBM 预测过高的血度和错误的预测SLS效应.
- 使用分子溶解药物的 PBBM 准确地预测了所有配方和条件的人类药物动力学概况.
结论:
- 只有药物的分子溶解 (自由) 分数可供直接口服吸收.
- 准确的生理学基础生物制药模型需要输入自由药物度,而不是总明显度.
- 这项研究证实了自由药物分数在预测口服生物利用率和改善IVIVC方面的关键作用.
关键词:
阿莱克提尼布 (Alectinib) 是一种药物.解散 解散 解散 是一个过程.启用配方使得配方成为可能.微透析是一种微透析.分子溶解的药物分子基于生理学的生物制药建模 (PBBM)溶解不良的药物 溶解不良的药物溶解化 溶解化更多相关视频
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