口服药物吸收中的药物溶解:研讨会报告
Kimberly Raines1, Payal Agarwal1, Patrick Augustijns2
1Food and Drug Administration, Center for Drug Evaluation and Research, White Oak, Maryland, USA.
The AAPS journal
|November 7, 2023
概括
本次研讨会探讨了用于口服吸收的药物溶解方面的挑战,重点关注无形固体分散和体外方法. 主要讨论涉及定义"溶解药物"和推进非补充性测试,以获得更好的生物制药预测.
科学领域:
- 制药科学 制药科学
- 生物制药生物制药公司
- 药物运输 药物运输 药物运输
背景情况:
- 工作坊 工作坊 的工作坊.
- 在口服药物吸收中的药物溶解.
- 召集专家讨论药物溶解的关键方面及其对口服药物吸收的影响.
- 关键主题包括无形固体分散 (ASD),溶解和透之间的相互作用,以及用于预测体内性能的体外方法的开发.
研究的目的:
- 识别和讨论与口服药物吸收相关的药物溶解科学的当前挑战和新兴趋势.
- 探索用于评估药物性能和预测体内结果的体外方法学的进步.
- 解决新型溶解测试方法的监管考虑和潜在障碍.
主要方法:
- 研讨会包括讲座和突破性会议,促进了关于特定主题的深入讨论.
- 关注的重点领域包括复杂介质中溶解药物的表征,标准溶解试验的局限性和非补充方法的应用.
- 讨论还涉及特殊情况和生物预测方法的潜在好处.
主要成果:
- 经常出现的主题突出了定义和测量"溶解药物"的复杂性,特别是在合体系统中溶解性差的药物.
- 在溶解测试中发现了传统水槽条件的局限性,促使人们探索非补充方法和条件.
- 生物预测性溶解方法对于监管目的的潜在实用性得到了认可,例如生物豁免器.
结论:
- 精确评估溶解药物,特别是难以溶解的化合物在具有挑战性的介质,仍然是一个关键的发展领域.
- 非补充溶解方法和条件为改善生物制药预测提供了希望,但面临监管接受障碍.
- 一种平衡的方法,可能整合质量控制和生物预测方法,可能是必要的药物产品全面评估.
相关概念视频
01:27Factors Influencing Drug Absorption: Drug Dissolution
527
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...
527
01:20Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
209
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...
209
01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
860
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...
860
01:21Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
1.4K
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...
1.4K
01:15Theories of Dissolution: Diffusion Layer Model
778
Dissolution, the process by which drug particles dissolve in a solvent, is explained by the diffusion layer model, a theoretical framework that simulates the absorption of oral drugs and allows us to analyze experimental data.
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
778
01:22Factors Influencing Drug Absorption: Physicochemical Parameters
302
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...
302