立即释放固体口服剂型的生物豁免专著:伊萨夫科纳硫酸
David Plano1, Niklas Rudolph1, Christoph Saal2
1Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, 60596 Frankfurt am Main, Germany.
Journal of pharmaceutical sciences
|November 11, 2023
概括
研究了一份基于生物制药分类系统 (BCS) 的生物豁免专著,用于isavuconazonium硫酸盐. 虽然该药物显示出快速溶解,但配方挑战可能会阻碍仅通过体外数据的通用批准.
科学领域:
- 制药科学 制药科学
- 药物开发 药物开发
- 监管科学 监管科学
背景情况:
- 硫酸伊萨夫科纳是伊萨夫科纳的前药物,是一种抗真菌药物.
- 前药 (BCS III类) 和母药 (BCS II类) 具有不同的生物制药分类系统 (BCS) 属性.
- 在体内,isavuconazonium硫酸盐表现为BCS I类药物,表明具有高溶解性和透性.
研究的目的:
- 评估基于BCS的isavuconazonium硫酸立即释放口服剂型生物豁免专著的可行性.
- 评估isavuconazonium硫酸盐是否适用于监管批准,使用体外数据代替体内生物等价性研究.
- 审查与原药生物豁免相关的风险,并分析配方特定的溶解限制.
主要方法:
- 对isavuconazonium硫酸盐的实验和文献溶解度和溶解数据的评估.
- 与监管指南 (FDA,EMA,ICH) 进行数据比较,用于基于BCS的生物豁免.
- 商业囊配方 (Cresemba) 的溶解概况分析.
主要成果:
- 硫酸伊萨夫科纳酸盐在水性介质中具有高溶解性,但不稳定.
- 活性药物成分 (API) 从囊含量中的溶解速度很快.
- 囊的材料限制了硫酸伊萨夫科纳的释放,阻碍了生物豁免的批准.
结论:
- 目前对基于BCS的生物豁免的监管准则是限制性的,特别是对于前药物.
- 配方因素,特别是囊外,是通过BCS-Biowaiver方法对isavuconazonium硫酸盐的通用批准构成重大障碍.
- 尽管API溶解迅速,但药物产品的整体性能可能由于配方限制而不能满足生物豁免标准.
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