拉曼技术在药物逆向工程中的应用

Application of Raman Technique in Pharmaceutical Reverse Engineering

逆向工程以目标产品进行逆向分析及研究,是仿制药开发过程中的一个重要环节,在目前的仿制药一致性评价中发挥显著功效。尽管物理、化学方法众多,但原研制剂的逆向工程分析仍然极具挑战、极其耗时。逆向工程的最终目的不仅是确定原研制剂中所有可能的化学成分,还要深入揭示其制剂原则和药物释放机制。而如何高效合理地应用各种分析技术,是深入了解原研药的第一步。文章概述了一种光谱技术——拉曼光谱在药物逆向分析工程中的实用性,特别介绍在某些情况下,当其他常用固态分析技术如X射线粉末衍射、差示扫描量热法等不适用时,拉曼光谱对原研制剂中药物活性成分(API)晶型的鉴定。文章通过对拉曼光谱在某些特定条件下应用的具体案例的演示,展示了分子振动相关光谱分析手段在药物逆向分析工程中的应用前景。

Pharmaceutical reverse engineering, a reverse analysis of the final drug product, is important for the development of generic formulations, and has played a critical role in the current quality consistency evaluation for generic drugs. Although various chemical and physical methods are available for deformulating a product, reverse engineering of innovator products can often be rather challenging and time consuming. The ultimate aim for reverse engineering is not only to identify all possible chemical components, but also to reveal the underlying formulation principles and release mechanisms. Efficient utilization of various analytical techniques is certainly the first step to achieve an insightful understanding of the innovator products. This review introduced the applications of one spectroscopic technique Raman spectroscopy in pharmaceutical reverse engineering, especially in identification ofAPI polymorph when other commonly employed solid state techniques such as X ray powder diffraction （XRPD） and Differential scanning calorimetry （DSC） are unsuccessful. Examples were presented to demonstrate how Raman spectroscopy was applied under those specific conditions, and to illustrate the potential future of the vibrational approaches in the pharmaceutical reverse engineering.