在双重和三重药物固定剂量组合产品中评估里法辛的多态纯度
Marina Antonio1, Mariano Raffaghelli2, Rubén M Maggio3
1Área de Análisis de Medicamentos, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario and Instituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario S2002LRK, Argentina.
Journal of pharmaceutical sciences
|October 2, 2023
概括
这项研究开发了近红外光谱学方法来分析固剂组合结核病药物中的里法辛多态性. 这些方法准确地评估了药物的纯度,确保了这些必需药物的安全性和有效性.
科学领域:
- 分析化学 分析化学
- 制药科学 制药科学
- 频谱学是一种光谱学.
背景情况:
- 第一线抗结核药物经常被组合成固定的剂量组合 (FDC),以改善患者的坚持治疗.
- 在FDC中,可变的生物可用性是一个重要的质量挑战,里芬素 (RIF) 固态特性是关键因素.
- RIF的多态性可能会影响包含RIF的FDC的性能和质量.
研究的目的:
- 开发和验证分析方法来评估RIF多态化对FDC业绩的影响.
- 使用开发的方法来评估商业RIF-ISH和PZA-RIF-ISH FDC产品.
- 为了将RIF多态形式与药物产品质量和生物可用性相关联.
主要方法:
- 开发和验证两种近红外 (NIR) 光谱法与部分最小平方 (PLS) 回归相结合的方法.
- 使用RIF Form I/Form II与其他活性药物成分 (API) 和辅助剂的混合物编制培训和验证套件.
- 数据预处理 (SNV-D) 和PLS因子的优化,随后使用商业FDC产品和X射线粉碎衍射验证.
主要成果:
- 在验证期间,双重和三重FDC产品的回收率达到令人满意的水平 (98.5±2.0%和98.7±1.8%).
- 该NIR-PLS模型准确地估计了RIF-ISH囊中的Form II多态纯度 (1.02 ± 0.02w/w).
- 在三重FDC片中检测到低的II型纯度 (0.800 ± 0.021w/w),由X射线粉末衍射证实,但溶解仍然很高 (99-102%).
结论:
- 开发的NIR-PLS方法对于在复杂的FDC配方中量化RIF多态形式是有效的.
- 三重FDC片中的80%的II型纯度并没有对溶解产生负面影响,这表明安全性和有效性得到维持.
- 尼尔光谱为含有RIF的FDC的质量控制提供了有价值的工具,解决了与多态性相关的生物可用性问题.
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