优化水友性药物纳入SEDDS使用干逆:对准备方法的比较研究
Sera Lindner1, Fabrizio Ricci1, Matthias Sandmeier1
1Thiomatrix Forschungs- und Beratungs GmbH, Trientlgasse 65, 6020, Innsbruck, Austria.
Drug delivery and translational research
|January 17, 2025
概括
有机溶剂辅助 (OS) 方法与干添加 (DA) 方法相比,在自乳化药物输送系统 (SEDDS) 中显著提高了水性药物溶解度和保留率. 在脂友性配方中,OS-RM的结合改善了药物输送和细胞吸收.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 制定 发展 制定 发展
背景情况:
- 水友性药物由于溶解性和生物可用性差,对口服药物构成挑战.
- 自乳化药物递送系统 (SEDDS) 是一种有前途的方法,可以提高脂性药物的溶解性和吸收性.
- 将水友性药物纳入SEDDS需要专门的配方策略,例如使用反向微粒 (RM).
研究的目的:
- 为了比较两种不同的干逆菌 (RM) 制备方法的疗效,将水友性药物纳入口服SEDDS中.
- 评估不同RM制备方法对SEDDS中的药物溶解性,保留和细胞吸收的影响.
主要方法:
- 研究了两种干燥RM制备方法:干燥添加 (DA) 和有机溶剂辅助 (OS).
- 含有特定表面活性剂和油 (squalane) 的水友型药物 (乙里丁乳酸盐,素盐,细素) 被纳入含有特定表面活性剂和油 (squalane) 的RM中.
- 该OS方法涉及在乙醇或2-醇中预溶解药物,然后蒸发溶剂.
主要成果:
- 运用OS方法,特别是用酸多和大豆酸胆,显著增加了药物溶解度 (对于乙他克里丁来说高达109倍).
- 与DA-RM相比,OS-RM的整合增强了SEDDS中的药物保留,并导致细胞吸收率提高了1.6倍.
- 虽然DA方法更简单,但OS方法在溶解和保留水友性药物方面表现出卓越的性能.
结论:
- 有机溶剂辅助 (OS) 方法是一种更有效的方法,用于提高高脂性SEDDS配方中的水友药物的溶解性和保留性.
- 将OS-RM纳入SEDDS提供了一个有前途的策略,用于改善具有挑战性的水友性药物化合物的口服输送.
- 对OS-RM制备的进一步研究可以优化SEDDS以提高药物的生物可用性.
相关概念视频
Factors Affecting Dissolution: Particle Size and Effective Surface Area
708
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...
708
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
173
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...
173
Factors Influencing Drug Absorption: Pharmaceutical Parameters
113
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
113
Factors Influencing Drug Absorption: Physicochemical Parameters
210
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...
210
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
1.0K
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...
1.0K
Factors Influencing Drug Absorption: Drug Dissolution
403
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...
403


