在中介胃肠道pH水平的生物相关二碳酸盐缓冲体中,有离子药物的溶解概况
Nanami Okamoto1, Kiyohiko Sugano2
1Molecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.
The AAPS journal
|November 10, 2025
概括
在中间GIpH下进行生物相关二碳酸盐缓冲器 (BCB) 溶解测试,显示出各种药物超和. 浮式盖子方法有效地防止了二氧化碳的损失,使可离子药物的可靠溶解档案成为可能.
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:
- 了解药物在胃肠道中的溶解对于预测口服吸收至关重要.
- 中间的GI pH条件,特别是那些涉及二碳酸盐缓冲区的条件,对药物行为有意义.
- 现有的溶解介质可能无法完全复制胃肠道复杂的生理环境.
研究的目的:
- 在中间GIpH下使用生物相关的二碳酸盐缓冲剂 (BCB) 调查可电离药物的溶解概况.
- 评估浮盖方法在溶解测试期间维持BCB稳定性的有效性.
- 为了比较BCB中的药物溶解和超和与综合性缓冲器 (酸和酸盐) 的比较.
主要方法:
- 用以控制pH和离子强度的BCB溶液 (5-20mM,pH3.0-5.0,I=0.14M) 的制备.
- 使用浮式盖子方法来防止BCB的二氧化碳损失.
- 在BCB,酸缓冲区 (CPB) 和乙酸缓冲区 (ACB) 中,在pH4.5时测试febuxostat,dipyridamole,dantrolene,pioglitazone HCl和tosufloxacin tosylate单水化合物的溶解.
主要成果:
- 使用浮式盖子方法,BCB证明2小时保持稳定的pH值 (变化≤±0.11).
- 与CPB和ACB相比,Febuxostat和Dipyridamole的溶解速度在BCB中较慢.
- 皮奥格利塔HCl在BCB的超和度明显高于CPB和ACB,而在CPB的超和度略低于dantrolene.
- 托苏夫洛克萨托西酸单酸表现出因离子存在而变化的超和,形成半化盐.
结论:
- 在BCB中,可电离药物的溶解概况与综合性缓冲器中的溶解概况不同,特别是在盐形式药物中.
- 在使用浮式盖子方法时,BCB是一种可行的溶解介质,可用于中间GI pH条件.
- 这些发现强调了使用生物相关介质来准确预测体内药物性能的重要性.
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