新的双相体外溶解方法正确预测了黄素在人类的口服生物可用性
Marvin Benedikt Brenner1, Sandra Flory2, Matthias Wüst3
1Department of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Pharmaceutical Institute, Gerhard-Domagk-Str. 3, 53121 Bonn, Germany.
Journal of agricultural and food chemistry
|October 12, 2023
概括
一种新的体外溶解方法BiPHa+准确地预测了复杂配方的体内黄素生物可用性. 与传统系统相比,这种方法提供了优越的体内相关表征.
科学领域:
- 药理动力学和药物输送方法
- 配方科学科学 配方科学
- 分析化学 分析化学
背景情况:
- 需要准确的体外溶解方法来预测复杂混合物中化合物的体内生物可用性.
- 现有的方法往往无法有效地与人类的药理动力学数据相关联.
- 由于其复杂的配方要求,黄素的生物可用性是一个重大挑战.
研究的目的:
- 开发和验证复杂的黄素配方的体内预测溶解方法 (BiPHa+).
- 评估BiPHa+在表征具有已知的体内生物可用性的黄素配方中的性能.
- 为改善配方评估建立体外-体内关系.
主要方法:
- 利用了生物可用性改善的黄素配方的人类药理学试验的数据.
- 应用了新的BiPHa+溶解方法来描述之前研究的八种黄素配方.
- 分析了黄素在水和有机层中的溶解,以了解释放特征.
- 已确立的BiPHa+和常规方法的体外-体内相关性 (IVIVC).
主要成果:
- 与传统系统相比,BiPHa+在黄素配方的体内相关表征方面表现出优异.
- 该方法精确地根据其对人类的生物可用性对所有测试配方进行了分类.
- 在体外-体内关系中,BiPHa+实现了很高的线性 (r2 = 0.9975).
- 溶解行为显示了水相中的配方依赖性减少和有机相中的稳定性.
结论:
- BiPHa+试验准确地预测了复杂混合物中库尔库米诺酸的体内生物可用性.
- BiPHa+为配方依赖的释放特征提供了有价值的机械洞察力.
- 这种新的方法提高了用于药物开发的体外溶解测试的可靠性.
相关概念视频
01:27Factors Influencing Drug Absorption: Drug Dissolution
535
The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
535
01:21Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
1.5K
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
1.5K
01:15Theories of Dissolution: Diffusion Layer Model
790
Dissolution, the process by which drug particles dissolve in a solvent, is explained by the diffusion layer model, a theoretical framework that simulates the absorption of oral drugs and allows us to analyze experimental data.
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
790
01:20Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
211
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...
211
01:23Factors Influencing Bioavailability: First-Pass Elimination
6.4K
When a drug is taken orally, it undergoes a journey starting from the gastrointestinal (GI) tract, passing through the portal vein, reaching the liver, and finally entering the systemic circulation. This process involves the absorption of the drug across the GI tract. The liver is the primary site for metabolizing the drug, with some metabolism also occurring in the gut wall. This journey significantly reduces the quantity of the drug that reaches the systemic circulation, a phenomenon known as...
6.4K
01:16Methods for Studying Drug Absorption: In vitro
238
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...
238