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Classification and Visualization of Physical and Chemical Properties of Falsified Medicines with Handheld Raman Spectroscopy and X-Ray Computed Tomography

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  • 1 Analytical Development, Pharmaceutical Sciences, Takeda Pharmaceutical Company, Ltd., Osaka, Japan;
  • | 2 Drug Management and Policy, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan;
  • | 3 Global Product Protection, Takeda Pharmaceuticals U.S.A., Inc., Deerfield, Illinois
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Analytical methods for the detection of substandard and falsified medical products (SFs) are important for public health and patient safety. Research to understand how the physical and chemical properties of SFs can be most effectively applied to distinguish the SFs from authentic products has not yet been investigated enough. Here, we investigated the usefulness of two analytical methods, handheld Raman spectroscopy (handheld Raman) and X-ray computed tomography (X-ray CT), for detecting SFs among oral solid antihypertensive pharmaceutical products containing candesartan cilexetil as an active pharmaceutical ingredient (API). X-ray CT visualized at least two different types of falsified tablets, one containing many cracks and voids and the other containing aggregates with high electron density, such as from the presence of the heavy elements. Generic products that purported to contain equivalent amounts of API to the authentic products were discriminated from the authentic products by the handheld Raman and the different physical structure on X-ray CT. Approach to investigate both the chemical and physical properties with handheld Raman and X-ray CT, respectively, promise the accurate discrimination of the SFs, even if their visual appearance is similar with authentic products. We present a decision tree for investigating the authenticity of samples purporting to be authentic commercial tablets. Our results indicate that the combination approach of visual observation, handheld Raman and X-ray CT is a powerful strategy for nondestructive discrimination of suspect samples.

Author Notes

Address correspondence to Tomoko Kakio, Analytical Development, Pharmaceutical Sciences, Takeda Pharmaceutical Company, Ltd., Osaka, Japan. E-mail: tomoko.kakio@takeda.com

Authors’ addresses: Tomoko Kakio, Kazunobu Moriguchi, Takashi Hiroshima, and Yukihiro Ikeda, Analytical Development, Pharmaceutical Sciences, Takeda Parmaceutical Company Limited, Osaka, Japan, E-mails: kakio.tomoko@gmail.com, kazunobu.moriguchi@takeda.com, takashi.hiroshima@takeda.com, and yukihiro.ikeda@takeda.com. Naoko Yoshida, Hirohito Tsuboi, and Kazuko Kimura, Drug Management and Policy, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan, E-mails: naoko@p.kanazawa-u.ac.jp, tsuboih@p.kanazawa-u.ac.jp, and kimurak@p.kanazawa-u.ac.jp. Susan Macha, Takeda Pharmaceuticals USA Inc., Global Product Protection, Deerfield, IL, E-mail: susan.macha@takeda.com.

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