在体外查方法的比较,以评估药品辅助剂对膜透性的影响
Tokio Morita1, Hiroyuki Yoshida1, Naomi Tomita1
1Division of Drugs, National Institute of Health Sciences, Tonomachi 3-25-26, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan.
International journal of pharmaceutics
|September 18, 2024
概括
药物辅助剂会影响肠道药物吸收. 这项研究比较了体外模型,发现大多数辅助剂在临床剂量下是安全的,但 Lauryl 硫酸盐 (SLS) 影响了透性.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 生物制药生物制药公司
背景情况:
- 药物辅助剂对于药物配方和生物可用性至关重要.
- 了解辅助剂对肠道药物吸收的影响对于开发等效配方至关重要.
- 在体外模型对于查辅助剂药物相互作用至关重要.
研究的目的:
- 用各种体外模型评估药物辅助剂对药物透性的影响.
- 为了比较三个不同的体外查方法的性能:预涂PAMPA,PermeaPadTM和Caco-2单层.
- 识别显著改变药物透性的辅助剂,并评估它们的度依赖作用.
主要方法:
- 使用了三个体外模型:预涂层并行人工膜透性测定 (PAMPA),PermeaPadTM和Caco-2细胞单层.
- 评估了14种不同的制药辅助剂在生物制药分类系统 (BCS) 的不同类别中对药物的透性的影响.
- 分析了度依赖的效应,以区分特定与非特定的相互作用和膜完整性问题.
主要成果:
- 预涂层的PAMPA与某些辅助剂 (例如,基烯纤维素,波维K30) 的低透性药物的透性增加.
- 与预涂层PAMPA相比,PermeaPadTM在较高度下保持了膜完整性.
- 在PAMPA和PermeaPadTM测定中,硫酸 (SLS) 降低了高度透的药物的透性,并损害了Caco-2细胞完整性,超过了其关键菌度.
结论:
- 大多数制药辅助剂,除了SLS,在临床相关度下不会显著影响药物膜透.
- 预涂层的PAMPA模型对辅助剂的作用高度敏感,适合保守的评估.
- 通过PermeaPadTM和Caco-2模型,可以在更高的辅助剂度下进行评估,而PermeaPadTM对潜在的有毒辅助剂是有利的.
更多相关视频
12:18Assembly of Cell Mimicking Supported and Suspended Lipid Bilayer Models for the Study of Molecular Interactions
Published on: August 3, 2021
3.5K
10:33A Method for Determination and Simulation of Permeability and Diffusion in a 3D Tissue Model in a Membrane Insert System for Multi-well Plates
Published on: February 23, 2018
25.2K
相关概念视频
01:16Methods for Studying Drug Absorption: In vitro
210
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
210
01:20Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
179
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
179