旧的多形态,新技术:使用低频拉曼光谱评估里托纳维尔结晶性
Manolya K Hatipoglu1, Yeakub Zaker1, Daniel R Willett1
1Division of Complex Drug Analysis, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, St. Louis, Missouri 63110, United States.
Analytical chemistry
|October 5, 2023
概括
开发了定量拉曼光谱法来检测药片中的利托纳维尔多态体. 低频拉曼 (LFR) 分析为药物质量控制提供了更快,更节省样本的X射线粉末衍射 (XRPD) 替代方案.
科学领域:
- 制药科学 制药科学
- 分析化学 分析化学
- 材料科学 材料科学 材料科学
背景情况:
- 里托纳维尔的低溶解度晶体形式 (形式II) 在市场上发现后需要重制成无形状态.
- 热挤出是稳定无形里托纳维尔的关键过程,防止结晶.
研究的目的:
- 开发和验证定量低频和中频拉曼光谱 (LFR和MFR) 方法.
- 在商用药片中表征里托纳维尔多态 (I型和II型).
- 将拉曼光谱与X射线粉末衍射 (XRPD) 进行多态度评估.
主要方法:
- 开发和验证了定量LFR和MFR光谱学.
- 来自多家制造商的商业里托纳维尔片在加速条件下 (40°C,75%RH) 储存.
- 评估了多态结晶,并与定量XRPD结果进行了比较.
主要成果:
- 在两个产品中发生了I型结晶,在另一个产品中发生了II型结晶,经过四周.
- 拉曼光谱检测显示,XRPD的检测极限与两种多态体的检测极限相似.
- 传输LFR允许在缩短测量时间 (10秒与XRPD的66分钟相比) 的平板电脑中直接识别和检测多态生物.
结论:
- LFR是一种可行的,快速的,无需样本准备的技术,用于评估在现实世界制药样本中的利托纳维尔多态性.
- 拉曼光谱技术提供了与XRPD类似的分析性能,但节省了大量的时间.
- 这种方法提高了药品质量控制和制造效率.
相关概念视频
01:26Raman Spectroscopy Instrumentation: Overview
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A conventional Raman spectrophotometer includes a laser source, a sample holding system, a wavelength selector, and a detector.
The monochromatic laser source, typically using visible or near-infrared radiation, generates a highly focused beam of light. This light interacts with the molecules of the sample, scattering some of the light. Liquid and gaseous samples are usually tested in ordinary glass capillaries, while solids can be analyzed as powders packed in capillaries or as potassium...
The monochromatic laser source, typically using visible or near-infrared radiation, generates a highly focused beam of light. This light interacts with the molecules of the sample, scattering some of the light. Liquid and gaseous samples are usually tested in ordinary glass capillaries, while solids can be analyzed as powders packed in capillaries or as potassium...
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01:20Raman Spectroscopy: Overview
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The underlying principle of Raman spectroscopy is based on the interaction between light and matter, specifically molecules' inelastic scattering of photons. When a monochromatic beam of light, typically from a laser source, interacts with a sample, most scattered light has the same frequency as the incident light. This is known as Rayleigh scattering.
However, a small fraction of the scattered light exhibits a frequency shift due to the exchange of energy between the incident photons and...
However, a small fraction of the scattered light exhibits a frequency shift due to the exchange of energy between the incident photons and...
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