用小规模双相溶解和同时溶解-透装置进行生物等价性预测 - 一个阿里皮普拉尔病例研究
Szabina Kádár1, Andrew Kennedy2, Samuel Lee2
1Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 3 Műegyetem rkp, H-1111, Budapest, Hungary.
概括
这项研究比较了两种用于预测药物等价性的体外系统. 在优化了测试条件后,这两种系统在预测最大血度 (Cmax) 和曲线下的面积 (AUC) 的生物等价性方面都达到了100%的准确性.
科学领域:
- 药理动力学和药物开发
- 在体外-体外相对应性研究研究.
- 生物制药生物制药公司
背景情况:
- 简单的溶解试验在预测体内药物性能方面存在局限性.
- 双相溶解和溶解-透 (D-P) 系统提供了改善的体外-体内相关性潜力.
- 检测条件和评估方法的完善对于在药物开发中有效使用这些系统至关重要.
研究的目的:
- 为了比较小体积DP和双相溶解系统的预测精度,用于生物等价性预测.
- 调查剂量依赖对这些小规模系统预测准确性的影响.
- 评估在预测药物吸收的机械模型中使用完整的体外流量概况.
主要方法:
- 小体积 (16-20毫升) D-P系统和小体积 (40-80毫升) 双相溶解装置的比较.
- 对五种含有阿里皮普拉 (ARP) 的销售药物产品的评估.
- 优化测定条件,包括剂量降低,以克服系统限制.
- 机械建模的应用 (消化肠道统一理论) 使用整个体外流量概况.
主要成果:
- 这两种系统都在预测最大血度 (Cmax) 比率与剂量降低策略的生物等价性方面实现了100%的准确性.
- 曲线下面积 (AUC) 比率的预测准确性与剂量无关,两种装置均显示100%的准确性.
- 使用整个体外流量概况的机械建模,准确预测在±15%的可接受范围内吸收的分数.
结论:
- 小容量DP和双相溶解系统,当优化时,可以准确预测Cmax和AUC比率的生物等价性.
- 剂量减少是提高小规模溶解系统预测性能的关键策略.
- 将全面的体外流量概况集成到机械模型中,为预测药物吸收率提供了可靠的方法.
相关概念视频
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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...
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01:21Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
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01:20Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
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01:15Theories of Dissolution: Diffusion Layer Model
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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.
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01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
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