了解脂质对人类肠液溶解能力的影响
Brecht Goovaerts1, Joachim Brouwers1, Zahari Vinarov2
1Drug Delivery and Disposition, KU Leuven, Leuven 3000, Belgium.
Molecular pharmaceutics
|November 19, 2024
概括
人体肠液 (HIF) 阶段分离显著影响药物的溶解性. 在HIF中的脂质分数增强了脂性药物溶解度,这是当前模拟肠液 (SIF) 错过的一个因素.
科学领域:
- 药理动力学和药物新陈代谢
- 胃肠道生理学 胃肠道生理学
- 配方科学科学 配方科学
背景情况:
- 人类肠道液体 (HIF) 呈现出分化成脂质和菌根的阶段分离.
- 当前的食状态模拟肠液 (SIF) 不能复制这种相位分离.
- 精确模拟肠道药物溶解需要了解HIF分量的作用.
研究的目的:
- 研究HIF相分离对脂友药物溶解性的影响.
- 为了比较HIF中的药物溶解率与当前SIF.
- 分析HIF成分对药物溶解能力的影响.
主要方法:
- 在禁食和食状态下从健康的志愿者那里收集了十二指肠液.
- 生成HIF池和分析药物的明显溶解度,分为和总分数.
- 评估液体组成 (脂质,胆盐,胆固醇,pH,蛋白质).
主要成果:
- 美联储国家SIF准确预测了平均细胞溶解度,但错过了HIF变异性.
- 在HIF中的脂质分数平均增加了13.9倍的脂友药物溶解度.
- 微粒脂质度的变化,受胆盐和pH的影响,与溶解能力有很强的相关性.
结论:
- 脂质分数对于在养状态下准确预测肠道药物溶解度至关重要.
- 目前的SIF模型低估了药物溶解度,因为缺乏相位分离.
- 了解HIF成分的变化是改善口服药物配方和输送的关键.
相关概念视频
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
1.1K
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...
1.1K
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
178
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...
178
Lipid Digestion
90.8K
Lipids are large molecules that are generally not water-soluble. Since most of the digestive enzymes in the human body are water-based, there are specific steps the body must take to break down lipids and make them available for use.
90.8K
Membrane Fluidity
11.0K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
11.0K
Factors Influencing Drug Absorption: Physicochemical Parameters
237
The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
237
Factors Influencing Drug Absorption: Drug Dissolution
422
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...
422


