使用精细的可开发性分类系统 (rDCS) 来指导口服配方的设计
Kristian Beran1, Eline Hermans2, René Holm3
1Fraunhofer Institute for Translational Medicine and Pharmacology, Frankfurt am Main, Germany; Janssen Pharmaceutica NV, Pharmaceutical & Material Sciences, Beerse, Belgium.
Journal of pharmaceutical sciences
|October 7, 2024
概括
精细的可开发性分类系统 (rDCS) 为口服药物配方提供了详细的,不使用动物的方法. 它提供了比生物制药分类系统 (BCS) 更细致的风险评估,有助于成功开发口服药物.
科学领域:
- 制药科学 制药科学
- 药物开发 药物开发
- 生物制药生物制药公司
背景情况:
- 评估生物制药风险对于口服药物配方开发至关重要.
- 像生物制药分类系统 (BCS) 这样的现有系统提供了基本的分类,但可能缺乏细微差别.
- 需要全面的,不使用动物的方法来指导配方设计.
研究的目的:
- 为了展示改进的可开发性分类系统 (rDCS) 框架的实际应用.
- 为各种活性药物成分 (API) 的口服配方设计提供指导.
- 将rDCS分类与BCS分类进行比较,并评估rDCS可靠性.
主要方法:
- 将先进的rDCS框架应用于六个不同的API.
- 使用rDCS和BCS的API的分类.
- rDCS和BCS分类的比较.
- 对rDCS预测与发展和药理动学的文献数据的验证.
主要成果:
- 与BCS相比,rDCS为几个API提供了更细致的风险评估.
- 乙氨基,伏利可纳和莱姆博雷克桑都被这两种系统有利地分类.
- 费德拉提尼布在rDCS中显示分层风险,取决于体内超和.
- 沃克塞洛托和伊斯特拉德菲林被归类为rDCSIIb类,表明需要提高溶解度.
结论:
- rDCS可靠地支持口服配方设计,跨越广泛的API特性.
- rDCS提供了一种全面的,不涉及动物的方法来评估生物制药风险.
- 这一框架为指导口服药物配方的开发提供了坚实的基础.
相关概念视频
Factors Affecting Dissolution: Particle Size and Effective Surface Area
753
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...
753
Factors Influencing Drug Absorption: Pharmaceutical Parameters
122
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...
122
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
179
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...
179
Factors Influencing Drug Absorption: Drug Dissolution
425
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...
425
Structure-Activity Relationships and Drug Design
676
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
676
Routes of Drug Administration: Enteral
3.3K
Medications can be administered through the enteral route using liquids, capsules, or tablets.
Enteral administration involves drug administration via the mouth in two ways: orally or sublingually.
Unlike sublingually drugs, drugs that are taken orally pass through the gastrointestinal (GI) tract and get metabolized by the liver. Once metabolized, the drug is absorbed into the systemic circulation, reaching different body parts via the bloodstream. However, while passing through the stomach,...
Enteral administration involves drug administration via the mouth in two ways: orally or sublingually.
Unlike sublingually drugs, drugs that are taken orally pass through the gastrointestinal (GI) tract and get metabolized by the liver. Once metabolized, the drug is absorbed into the systemic circulation, reaching different body parts via the bloodstream. However, while passing through the stomach,...
3.3K


