胃肠道生物分子对制药颗粒物固态转化的影响
Anas Aljabbari1, Shinji Kihara1, Thomas Rades1
1Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
Molecular pharmaceutics
|July 26, 2023
概括
胃肠道生物分子通过形成冠状体来改变药物的固态转换,影响无形到晶体通路. 低频拉曼光谱检测显示,在养状态条件下,抑制的中间形式和减少的粒子聚合.
科学领域:
- 制药科学 制药科学
- 固态化学 固态化学
- 生物物理化学 生物物理化学
背景情况:
- 口服药物管理涉及与胃肠道液体相互作用的固体剂型.
- 被吸附的生物分子形成的"胃肠冠状"可以影响药物的固态行为.
- 了解这些转变对于预测药物溶解和生物可用性至关重要.
研究的目的:
- 为了在现场研究无形印梅他辛的固态相位转换.
- 评估生物相关条件 (温度,pH) 和生物分子对这些转变的影响.
- 探索低频拉曼 (LFR) 光谱在研究这些动态过程中的作用.
主要方法:
- 作为一个模型系统,使用了灭式无形印米他辛.
- 实验在37°C和pH值1.2-6.8进行,有和没有胆盐/脂混合物.
- 在现场使用低频拉曼 (LFR) 光谱进行固态分析.
- 通过时间解析的同步子小和广角X射线散射 (SAXS/WAXS) 进行对照.
主要成果:
- 观察到一种修改的固态转化途径,从无形转化为晶体的印米他辛.
- 添加胃肠道生物分子抑制了在pH值6.8.8时观察到的中间e型.
- 胆盐/脂混合物在酸性pH (≤4.5) 时降低了颗粒聚合.
- 生物分子抵消了药物的疏水性和生理温度的塑化效应.
结论:
- 内源性胃肠道生物分子显著影响溶解介质中的药物分子的固态特征.
- 胃肠冠状形成影响药物相变化和粒子行为.
- 低频拉曼光谱 (LFR) 是实时固态分析的宝贵工具,提供了其他技术难以获得的洞察力.
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