基于并行人工膜透性分析的塔拉佐辛化片的生物等价性分析
Jianzhao Niu1, Hanhan Huang1,2, Ming Ji3
1NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing 100050, China.
Pharmaceuticals (Basel, Switzerland)
|August 29, 2024
概括
扩大规模的PAMPA试验MacroFlux确定了一些通用现在酸片的生物等价性风险. 发现活性药物成分属性,而不是辅助成分,是潜在生物不等价性的首要原因.
科学领域:
- 药理动力学和药物输送方法
- 膜运输研究 膜运输研究
- 药品分析 药品分析
背景情况:
- 平行人工膜透性试验 (PAMPA) 是评估化合物在脂质双层中的透性的关键方法.
- 宏流体 (MacroFlux) 是一种扩大规模的PAMPA方法,旨在提高体内药物性能的预测.
- 泰拉索因化 (TH) 片的生物等价性对于确保治疗疗效和患者安全至关重要.
研究的目的:
- 通过使用MacroFlux测定来评估通用现在酸 (TH) 片的生物等价性.
- 为了比较一个参考TH配方与七个通用版本的溶解概况和透性.
- 确定在MacroFlux测定中观察到的潜在生物等效差异的因素.
主要方法:
- 利用MacroFlux,一个扩大规模的并行人工膜透性测试 (PAMPA),以评估药物透.
- 在四种不同的介质中比较了参考和通用现在酸 (TH) 片的溶解概况.
- 雇佣的μFlux测定用于调查活性药物成分 (API) 属性和辅助剂配方对透性的影响.
主要成果:
- 在所有测试的介质中,通用TH片的溶解概况与参考配方相当.
- 几种通用TH片表现出较低的流量和MacroFlux的总透量,低于接受标准.
- 活性药物成分 (API) 属性被确定为生物不等价风险的主要驱动因素,而辅助剂没有显著影响.
结论:
- 宏流量试验作为一个有价值的辅助工具,用于预测仿制药的体内生物等价性.
- 活性药物成分 (API) 特征的变化是现在酸 (TH) 配方中生物等价性风险的一个主要问题.
- 辅助剂的组成似乎没有显著影响在测试的通用TH片内生物等价性风险.
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