药物载荷和微环境pH在产生纳米物种中的作用 在溶解基于尤德拉吉特的无形固体分散过程中
Soumalya Chakraborty1, Utsab Mondal1, Arvind K Bansal1
1Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab-160062, India.
Molecular pharmaceutics
|June 2, 2025
概括
在无形固体分散 (ASD) 溶解过程中纳米物种的形成是复杂的. 离子聚合物相互作用和微环境pH影响纳米物种的产生,可能是通过未水层中的液态-液态相分离.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 物理化学 物理化学
背景情况:
- 无形固体分散 (ASDs) 提高了药物的溶解性和生物可用性.
- 在ASD溶解过程中形成纳米物种是生物制药性能的一个关键因素.
- 了解以离子聚合物为基础的ASD溶解机制对于药物配方至关重要.
研究的目的:
- 为了研究在阿普雷皮坦 (APR) 溶解过程中纳米物种形成的机制-Eudragit L100-55 ASDs.
- 阐明药物负载和微环境pH对纳米物种产生的影响.
- 探索潜在的机制,包括液-液相分离 (LLPS) 和离子对形成.
主要方法:
- 表面正常释放 (SNR) 测试.
- 粉末X射线衍射 (pXRD) 用于结晶性分析.
- 同焦激光扫描显微镜 (CLSM) 和偏光显微镜 (PLM) 用于相隔分析.
- 不水层 (UWL) 模拟.
主要成果:
- 在所有药物装载中观察到APR和Eudragit L100-55的同等释放.
- 散装介质中纳米物种的形成仅在较低的药物负载 (5 和 20% w/w) 时才发生.
- 在水合的ASD表面上没有结晶性和无形-无形相分离 (AAPS).
- 微环境pH,受药物负载的影响,影响APR无形溶解度.
- 在UWL和离子对形成中的LLPS被确定为潜在的纳米物种生成机制.
结论:
- 基于离子聚合物的ASD溶解是复杂的,涉及复杂的药物-聚合物相互作用.
- 纳米物种的产生受到微环境pH值和药物负载的显著影响.
- 在UWL中的LLPS和离子对形成是这个系统中纳米物种形成的关键机制.
- 结果为设计使用离子聚合物有效的ASD提供了洞察力.
相关概念视频
Factors Affecting Dissolution: Particle Size and Effective Surface Area
1.1K
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...
1.1K
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
2.0K
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...
2.0K
Factors Influencing Drug Absorption: Pharmaceutical Parameters
198
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...
198
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
407
Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
407
Factors Influencing Drug Absorption: Drug Dissolution
734
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...
734
Factors Influencing Drug Absorption: Physicochemical Parameters
458
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...
458


