在固态状态下稳定生物学的分子机制.
Jing Ling1, Yong Du2, W Peter Wuelfing1
1Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., Rahway, NJ 07065, USA.
Journal of pharmaceutical sciences
|December 1, 2024
概括
固态生物药物通过糖替代和矩阵玻璃化来增强蛋白质药物稳定性. 了解这些机制有助于设计更稳定的蛋白质药物配方.
科学领域:
- 生物物理学的生物物理.
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
背景情况:
- 由于其复杂的结构和动态,蛋白质药物面临着稳定性挑战.
- 固态配方与生物制剂的液态配方相比,提供了更好的稳定性.
- 了解稳定机制对于有效的药物产品设计至关重要.
研究的目的:
- 审查固态配方中蛋白质药物稳定性的分子机制.
- 阐明水为糖的替代和矩阵玻璃化的作用.
- 为设计稳定的固体生物药物产品提供科学依据.
主要方法:
- 使用先进的生物物理技术进行实验调查的审查.
- 分析蛋白质结构和蛋白质与辅助剂的相互作用.
- 在各种状态下评估分子动力学和微环境属性.
主要成果:
- 详细检查热力学和动力学稳定模型.
- 蛋白质-糖和蛋白质-盐的混合性和微环境酸度的阐明.
- 对影响蛋白质稳定性的分子级相互作用的洞察.
结论:
- 机理性理解有助于预测蛋白质药物稳定性.
- 这些知识使得固体生物制药产品的合理设计成为可能.
- 先进的生物物理技术是分析固态蛋白质行为的关键.
相关概念视频
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
177
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...
177
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
287
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...
287
Factors Influencing Drug Absorption: Pharmaceutical Parameters
121
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...
121
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
Biopharmaceutics and Pharmacokinetics: Overview
1.8K
Understanding drugs, drug products, and their performance in pharmaceutical science is pivotal. Drugs, whether simple molecules or complex compounds, are designed to interact with the body's biological systems to diagnose, treat, or prevent diseases. Drug products include various delivery systems such as tablets, capsules, injections, and inhalers. The performance of these drug products is gauged by their ability to deliver the active ingredient to the desired site of action at the...
1.8K
Drug Distribution: Tissue Binding
2.6K
Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
For...
For...
2.6K


