结合超和溶解配方的好处 - - 两种配方比一种更好吗?
Caroline Alvebratt1, Filip Karlén1, Michelle Åhlén2
1Department of Pharmacy, Uppsala Biomedical Centre, P.O. Box 580, Uppsala University, Uppsala SE-751 23, Sweden.
International journal of pharmaceutics
|July 13, 2024
概括
这项研究开发了一种先进的体外模型,用于预测基于脂质的配方 (LBF) 和无形固体分散 (ASD) 等复杂配方的口服药物吸收. 该模型成功地将体外表现与体内结果相关联,有助于配方开发.
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:
- 口服药物吸收不良是一个重大挑战,通常是由于胃肠道溶解不足.
- 需要进行体外测试来预测激活配方的体内性能,考虑溶解,消化和透.
- 启用吸收 (ENA) 装置已经显示出对评估基于脂质的配方 (LBFs) 的承诺.
研究的目的:
- 用Caco-2细胞或人工脂质膜的启用吸收装置 (ENA) 评估基于脂质的配方 (LBF) 和无形固体分散 (ASD) 的性能.
- 评估结合LBF和ASD策略的潜在好处.
- 为了确定这些复杂配方的体外-体内相关性 (IVIVC).
主要方法:
- 使用了一种具有两个设置的启用吸收 (ENA) 装置:Caco-2细胞单层和人工脂质膜.
- 测试了基于脂质的配方 (LBF),无形固体分散 (ASD) 和ASD与空白LBF的组合.
- 在老鼠身上进行了体内药理动力学研究,以评估体外-体内相关性.
主要成果:
- 在ENA装置中,高度的药物并不能确保高质量转移,特别是在ASD与LBF相比.
- 无形固体分散 (ASD) 显示了依赖pH的溶解性问题,导致体内性能差.
- 将ASD与空白LBF相结合,改善了体外溶解,并在体内显著增加了药物暴露.
结论:
- 在体外启用吸收 (ENA) 模型有效地捕捉了溶解度的限制,并展示了克服这些限制的策略.
- 在非pH敏感配方的体内药物暴露和ENA装置AUC之间观察到良好的相关性.
- 先进的体外模型成功地解释了复杂药物输送配方的吸收差异.
相关概念视频
Solution Formation
31.4K
There is no one solvent that can dissolve every type of solute. Some substances that readily dissolve in a certain solvent might be insoluble in a different solvent. A simple way to predict which substances dissolve in which solvent is the phrase "like dissolves like". This means that polar substances, such as salt and sugar, dissolve in a polar substance like water. In contrast, non-polar substances are more soluble in non-polar solvents such as carbon tetrachloride.
This selective...
This selective...
31.4K
Colloidal precipitates
546
The high insolubility of some precipitates can result in an unfavorable relative supersaturation. This can lead to colloidal particles with a large surface-to-mass ratio, where adsorption is promoted. For instance, in the precipitation of silver chloride, silver ions are adsorbed on the surface of the colloidal particles, forming a primary layer. This layer attracts ions of opposite charge (such as nitrate ions), forming a diffuse secondary layer of adsorbed ions. This electric double layer...
546
Combined Effects of Drugs: Synergism
3.8K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
3.8K
Factors Affecting Dissolution: Particle Size and Effective Surface Area
794
Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are...
794
Solubility
17.4K
Solution, Solubility, and Solubility Equilibrium
A solution is a homogeneous mixture composed of a solvent, the major component, and a solute, the minor component. The physical state of a solution—solid, liquid, or gas—is typically the same as that of the solvent. Solute concentrations are often described with qualitative terms such as dilute (of relatively low concentration) and concentrated (of relatively high concentration).
In a solution, the solute particles (molecules,...
A solution is a homogeneous mixture composed of a solvent, the major component, and a solute, the minor component. The physical state of a solution—solid, liquid, or gas—is typically the same as that of the solvent. Solute concentrations are often described with qualitative terms such as dilute (of relatively low concentration) and concentrated (of relatively high concentration).
In a solution, the solute particles (molecules,...
17.4K
Chemical and Solubility Equilibria
4.1K
The free energy change associated with dissolving a solute in a liter of solvent is called the free energy of a solution, ΔGsolution. The overall ΔGsolution is expressed as the balance of ΔGinteraction against the always-favorable free-energy of mixing, ΔGmixing. Solution formation is favorable if ΔGsolution is less than zero, whereas it is unfavorable if ΔGsolution is greater than zero. In short, for a solution to form and complete dissolution to take place,...
4.1K


