通过采用实验设计来开发阿比拉酸的高效过程
Shravan Kumar Komati1,2, Mukesh Kumar Madhra2, Amarendhar Manda1,2
1Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India.
ACS omega
|July 15, 2024
概括
这项研究优化了使用设计质量 (QbD) 和实验设计 (DoE) 的阿比拉酸合成. QbD方法提高了工艺效率,控制了关键杂质,提高了整体产品质量和产量.
科学领域:
- 制药化学 制药化学 制药化学
- 过程化学 过程化学
- 药物合成 药物合成
背景情况:
- 阿比拉酸是前列腺癌治疗的关键药物.
- 高效和高纯度的合成对于制药制造至关重要.
- 现有的合成路线可能面临杂质控制和产量方面的挑战.
研究的目的:
- 为了开发一个有效的合成过程的阿比拉酸.
- 应用设计质量 (QbD) 原则和实验的统计设计 (DoE).
- 识别和控制关键质量属性 (CQA),材料属性 (MA) 和关键过程参数 (CPP).
主要方法:
- 通过设计 (QbD) 实现质量原则.
- 实验的统计设计 (DOE) 用于过程优化.
- 风险评估以确定水,乙烯酸和最终API合成中的关键因素.
主要成果:
- 成功控制关键杂质:脱糖,17-甲基,氧和二烯杂质.
- 在中间产品和最终的API中实现了高选择性 (95%,85%,82%) 和纯度 (99%,96%,99%).
- 通过DoE识别的参数优化,从25%提高到57%的过程吞吐量.
结论:
- QbD和DoE的方法使阿比拉酸的高效和强大的合成成为可能.
- 这种优化的工艺通过最小化关键杂质来提高产品质量.
- 开发的方法提供了一个可扩展和改进的制造过程,为abiraterone酸.
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