基于粉末属性的新型指数,用于预测多组分制药混合物的分离风险
Jingzhe Li1, Zankrut Vyas2, Claudius Weiler3
1Boehringer Ingelheim Pharmaceuticals Inc., Department of Material and Analytical Sciences, Ridgefield, CT 06877, USA.
International journal of pharmaceutics
|July 22, 2025
概括
这项研究开发了新的指数,以预测药品混合物中的粉末分离. 这些指数有助于早期识别配方风险,确保药物的统一分发和产品质量.
科学领域:
- 制药制造业 制药制造业 制药制造业
- 材料科学 材料科学 材料科学
- 化学工程是化学工程的重要组成部分.
背景情况:
- 粉末分离是制药生产中的一个主要挑战,由于活性成分分布不均,影响药品质量.
- 了解分离驱动因素对于开发稳定有效的药物配方至关重要.
研究的目的:
- 为了评估不同活性药物成分 (API),辅助剂,药物负载和比例的药物混合物的粉末分离行为.
- 开发和验证用于评估分离风险的预测指数在早期的配方开发阶段.
主要方法:
- 使用近红外 (NIR) 光谱技术进行模型API (乙胺,布洛芬) 的内容分析.
- 采用修改后的 Jenike 和 Johanson 测试器来评估粉末混合物的分离倾向.
- 进行统计分析以确定关键的配方变量及其相互作用.
主要成果:
- 确定了配方变量 (药物负载,辅助剂比率) 之间的显著相互作用.
- 颗粒大小分布和流量特征是影响分离的关键因素.
- 开发了一种修改后的分离指数和两个复合参数指数,通过商业混合物验证,显示与材料特性有更好的相关性.
结论:
- 确定了预测隔离风险的关键参数 (D50,D90/D10,流动性,尺寸分布宽度).
- 开发的复合指数为早期配方开发中的快速隔离风险评估提供了一个实用的工具.
- 这种方法有助于创建强大的药物配方,使分离风险降到最低.
相关概念视频
Factors Influencing Drug Absorption: Pharmaceutical Parameters
193
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...
193
Factors Influencing Drug Absorption: Physicochemical Parameters
441
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...
441
Factors Affecting Drug Distribution: Miscellaneous Factors
534
Drug distribution in the human body is a complex process influenced by various individual factors, including age, pregnancy, obesity, diet, body water composition, pH levels, and specific disease conditions.
Age plays a significant role due to differences in body composition among different age groups. Infants, for instance, have a higher proportion of total body water and lower albumin levels, a protein that binds drugs in the bloodstream. This unique composition in infants enhances the...
Age plays a significant role due to differences in body composition among different age groups. Infants, for instance, have a higher proportion of total body water and lower albumin levels, a protein that binds drugs in the bloodstream. This unique composition in infants enhances the...
534
Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
127
Noncompartmental analyses offer an alternative method for describing drug pharmacokinetics without relying on a specific compartmental model. In this approach, the drug's pharmacokinetics are assumed to be linear, with the terminal phase log-linear. This assumption allows for simplified analysis and interpretation of the drug's behavior in the body.
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
127
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
268
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...
268
Factors Affecting Drug Biotransformation: Physicochemical and Chemical Properties of Drugs
380
A drug's physicochemical properties fundamentally influence its metabolism. For instance, a drug's molecular size and shape critically determine its interaction with enzymes and transporters — larger drugs may face difficulty reaching enzyme active sites, altering their metabolic pathways. The pKa of a drug, which establishes its ionization state, can impact its solubility and absorption, thereby influencing metabolism.
The drug's acidity or basicity is essential in...
The drug's acidity or basicity is essential in...
380


