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结构性洞察力新的治疗性深层体系统与酸使用1D,2DNMR和DSC技术与优越的肠道透性
Bayan Alkhawaja1, Faisal Al-Akayleh1, Jehad Nasereddin2
1Faculty of Pharmacy and Medical Sciences, University of Petra Amman Jordan falakayleh@uop.edu.jo.
RSC advances
|May 8, 2024
概括
治疗性深层浸泡溶剂 (THEDS) 为droperidol和aripiprazole等药物提供了一种绿色配方方法. 这些新型配方增强了药物吸收和药物动力学特性,证明了药物开发的有希望的进步.
科学领域:
- 制药科学 制药科学
- 绿色化学 绿色化学
- 药物输送系统 药物输送系统
背景情况:
- 治疗性深度环氧溶剂 (THEDS) 是制备活性药物成分 (API) 的环保替代品.
- 之前的研究已经为RISPERIDONE,芬太尼和LEVOFLOXACIN建立了THEDS,所有这些都具有循环三级氨基核.
- 酸 (CA) 已被确定为形成这些THEDS的合适成分.
研究的目的:
- 为了研究THEDSs的形成和特征,使用德罗皮多尔和阿里皮普拉与酸.
- 阐明THEDS形成的潜在热力学机制和区域化学.
- 评估这些新型配方的药理学影响,特别是药物流量.
主要方法:
- 液态1D和2D核磁共振 (NMR) 光谱仪用于结构阐明.
- 差分扫描热量计 (DSC) 用于热力学分析.
- 扭转肠囊技术,以评估药物透和流量.
- 扩散有序光谱 (DOSY) NMR用于研究扩散系数.
主要成果:
- 核磁共振分析证实了循环三级氨基核在药物-CA相互作用中的关键作用,由质子下场转移证明.
- DOSY NMR显示,THEDS内CA的扩散系数显著下降,这表明复杂的形成.
- 热分析显示,滴滴醇和阿里皮普拉倾向于化成无形固体,而不是在化后再结晶.
- 基于滴滴醇的THEDS显示了增强的吸收和流量,根据Everted gut sac技术进行评估.
结论:
- 循环三级氨基分子是THEDS中形成稳定的相互作用的关键.
- THEDS提供了一种绿色和有效的方法来创建API的液态配方.
- 这些配方表现出改善的药物动力学特性,如增强的吸收和流量,为先进的药物输送铺平了道路.
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