(621g) An Application of Portable Raman Spectroscopy for Rapid and Intact Polymorphism Quantitative Analysis of Multi-Component Pharmaceutical Tablets

An Application of Portable Raman spectroscopy for Rapid
and Intact Polymorphism Quantitative Analysis of Multi-component Pharmaceutical
Tablets

Yufeng Quan ^{1, 2, ¡ì}, Zhixuan
Huang ^3,¡ì , Lina Jia ^{1, 2} , Yun Cao ^{1, 2},Junbo
Gong ^{1, 2,} *, Da
Chen ^3, *

¹ National Engineering
Research Center of Industry Crystallization Technology, Tianjin, China;
² Collaborative Innovation Center of Chemical Science and
Engineering (Tianjin), Tianjin, China;

³ State
Key Laboratory of Precision Measurement Technology and Instruments, Tianjin

University,
Tianjin, China

¡ì
These authors contributed equally to this work and should be considered as
co-first authors.
*junbo_gong@tju.edu.cn

 *dachen@tju.edu.cn

Keywords: portable
Raman spectroscopy, polymorphism quantitative analysis, pharmaceutical tablets

Polymorphism
phenomenon is common and important among pharmaceutical products. On the one
hand, changes from one polymorph to another may have a big effect on the
bioavailability of the final products. One the other hand, a particular form of
an active pharmaceutical ingredient (API) represents an opportunity to prolong
the patent protection period which will bring a certain economic benefit. In
this study, a detailed application of portable Raman spectroscopy (a weight of
only 1.5kg), equipped with a micro sample platform, was performed on
Vortioxetine hydrobromide tablets in the presence of five different excipients for
qualitative and quantitative analysis. API is usually under the interference of
the auxiliary materials and the substance so that a chemo metrics algorithm was
applied to extract the API¡¯s Raman signal from tablets. The algorithm adopted a
prior knowledge-oriented feature extraction, which gets the main pure excipient
spectral information through the removal of fluorescence interference. Then,
the spectrum fitting method was used to analyze the information of the
interference components, such as the auxiliary materials, from the complex
spectrum of the tablets, and the intensity information of the API in the tablets
was extracted by the differential spectrum method. The results (shown in Fig.1
and Fig.2) demonstrates that this method is more effective than the traditional
fitting algorithm to overcome the interference of different contents of the
auxiliary material to the spectrum. Furthermore, combined with a
movable platform, the whole surface of each tablet can be detected to reduce
uncertainty.

Fig.1 Raman
spectroscopy of ¦Á form, ¦Â form and excipients tablets

Fig.2
Raman spectroscopy of polymorph mixtures (bottom line) and reconstructed
spectrum