1921
Volume 97, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

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.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.16-0971
2017-09-07
2018-09-23
Loading full text...

Full text loading...

/deliver/fulltext/14761645/97/3/tpmd160971.html?itemId=/content/journals/10.4269/ajtmh.16-0971&mimeType=html&fmt=ahah

References

  1. Pharmaceutical Security Institute, 2016. Available at: http://www.psi-inc.org/geographicDistributions.cfm. Accessed June 19, 2016.
  2. Yoshida N, Khan MH, Tabata H, Darath E, Sovannarith T, Kiet HB, Nivanna N, Akazawa M, Tsuboi H, Kimura K, , 2014. A cross-sectional investigation of the quality of selected medicines in Cambodia in 2010. BMC Pharmacol Toxicol 15: 13.
  3. Takahashi N, Tsuboi H, Yoshida N, Tanimoto T, Khan MH, Kimura K, , 2013. Investigation into the antinfluenza agent oseltamivir distributed via the internet in Japan. Ther Innov Regul Sci 47: 699705.
  4. Kimura K, Honma T, Tanimoto T, Takao C, Okumura J, Yoshida N, Akazawa M, , 2011. Public health implications of personal import of medicines through internet brokers (2); buying anti-obesity agents on-line. Jf Health Care Soc 21: 5567.
  5. Khan MH, Okumura J, Sovannarith T, Nivanna N, Akazawa M, Kimura K, , 2010. Prevalence of counterfeit anthelminthic medicines: a cross-sectional survey in Cambodia. Trop Med Int Health 15: 639644.
  6. Khan MH, Okumura J, Sovannarith T, Nivanna N, Nagai H, Tara M, Yoshida N, Akazawa M, Tanimoto T, Kimura K, , 2011. Counterfeit medicines in Cambodia: possible causes. Pharm Res 28: 484489.
  7. Newton PN, , 2001. Fake artesunate in southeast Asia. Lancet 357: 19481950.
  8. Newton PN, , 2008. A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia. PLoS Med 5: e32.
  9. Hall KA, Newton PN, Green MD, De Veij M, Vandenaabele P, Pizzanelli D, Mayfong M, Dondorp A, Fernández F, , 2006. Characterization of counterfeit artesunate antimalarial tablets from southeast Asia. Am J Trop Med Hyg 75: 804811.
  10. World Health Organization, 2015 Definitions of Substandard and Falsified (SF) Medical Products. Available at: http://www.who.int/medicines/regulation/ssffc/definitions/en/. Accessed May 14, 2016.
  11. World Health Organization. 2016. Substandard, spurious, falsely labelled, falsified and counterfeit (SSFFC) medical products. Available at: http://www.who.int/mediacentre/factsheets/fs275/en/. Accessed June 19, 2016.
  12. European Union, 2013. European Commission, Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use. Official Journal of the European Union 56: C343/01. (2103/C 343/01).
  13. Ranieri N, , 2014. Evaluation of a new handheld instrument for the detection of counterfeit artesunate by visual fluorescence comparison. Am J Trop Med Hyg 91: 920924.
  14. de Peinder P, Vredenbregt MJ, Visser T, de Kaste D, , 2008. Detection of Lipitor counterfeits: a comparison of NIR and Raman spectroscopy in combination with chemometrics. J Pharm Biomed Anal 47: 688694.
  15. Mazurek S, Szostak R, , 2006. Quantitative determination of captopril and prednisolone in tablets by FT-Raman spectroscopy. J Pharm Biomed Anal 40: 12251230.
  16. Mazurek S, Szostak R, , 2008. Quantitative determination of diclofenac sodium in solid dosage forms by FT-Raman spectroscopy. J Pharm Biomed Anal 48: 814821.
  17. Ricci C, Eliasson C, Macleod NA, Newton PN, Matousek P, Kazarian SG, , 2007. Characterization of genuine and fake artesunate anti-malarial tablets using Fourier transform infrared imaging and spatially offset Raman spectroscopy through blister packs. Anal Bioanal Chem 389: 15251532.
  18. Ricci C, Nyadong L, Yang F, Fernandez FM, Brown CD, Newton PN, Kazarian SG, , 2008. Assessment of hand-held Raman instrumentation for in situ screening for potentially counterfeit artesunate antimalarial tablets by FT-Raman spectroscopy and direct ionization mass spectrometry. Anal Chim Acta 623: 178186.
  19. Dowell FE, Maghirang EB, Fernandez FM, Newton PN, Green MD, , 2008. Detecting counterfeit antimalarial tablets by near-infrared spectroscopy. J Pharm Biomed Anal 48: 10111014.
  20. Lopes MB, Wolff J-C, , 2009. Investigation into classification/sourcing of suspect counterfeit Heptodintrade mark tablets by near infrared chemical imaging. Anal Chim Acta 633: 149155.
  21. Rodionova OYe, Pomerantsev AL, , 2010. NIR-based approach to counterfeit-drug detection. Trends Analyt Chem 29: 795803.
  22. Puchert T, Lochmann D, Menezes JC, Reich G, , 2010. Near-infrared chemical imaging (NIR-CI) for counterfeit drug identification: a four-stage concept with a novel approach of data processing (Linear Image Signature). J Pharm Biomed Anal 51: 138145.
  23. Been F, Yves RKD, Esseiva P, Margot P, , 2011. Profiling of counterfeit medicines by vibrational spectroscopy. Forensic Sci Int 211: 83100.
  24. Xiang D, Lobrutto R, Cheney J, Wabuyele B, Berry J, Lyon R, Wu H, Khan MA, Hussain AS, , 2009. Evaluation of transmission and reflection modalities for measuring content uniformity of pharmaceutical tablets with near-infrared spectroscopy. Appl Spectrosc 63: 3347.
  25. Xiang D, Berry J, Buntz S, Gargiulo P, Cheney J, Joshi Y, Wabuyele B, Wu H, Hamed M, Hussain AS, Khan MA, , 2009. Robust calibration design in the pharmaceutical quantitative measurements with near-infrared (NIR) spectroscopy: avoiding the chemometric pitfalls. J Pharm Sci 98: 11551166.
  26. Rantanen J, Räsänen E, Tenhunen J, Känsäkoski M, Mannermaa J-P, Yliruusi J, , 2000. In-line moisture measurement during granulation with a four-wavelength near infrared sensor: an evaluation of particle size and binder effects. Eur J Pharm Biopharm 50: 271276.
  27. De Beer T, Burggraeve A, Fonteyne M, Saerens L, Remon JP, Vervaet C, , 2011. Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes. Int J Pharm 417: 3247.
  28. Kakio T, Hiroshima T, Ikeda Y, , 2014. Development of quantitative analysis for polymorph of drug substances in pharmaceutical oral dosage forms by XRPD and raman spectroscopy. J Pharm Mach Eng 23.
  29. Newman AW, Byrn SR, , 2003. Solid-state analysis of the active pharmaceutical ingredient in drug products. Drug Discov Today 8: 898905.
  30. Holzgrabe U, Malet-Martino M, , 2011. Analytical challenges in drug counterfeiting and falsification-The NMR approach. J Pharm Biomed Anal 55: 679687.
  31. Shen Y-C, , 2011. Terahertz pulsed spectroscopy and imaging for pharmaceutical applications: a review. Int J Pharm 417: 4860.
  32. Sacre P-Y, De Bleye C, Chavez P-F, Netchacovitch L, Hubert Ph, Ziemons E, , 2014. Data processing of vibrational chemical imaging for pharmaceutical applications. J Pharm Biomed Anal 101: 123140.
  33. Stephenson GA, Forbes RA, Reutzel-Edens SM, , 2001. Characterization of the solid state: quantitative issues. Adv Drug Deliv Rev 48: 6790.
  34. Wold S, Trygg J, Berglund A, Antti H, , 2001. Some recent developments in PLS modeling. Chemom Intell Lab Syst 58: 131150.
  35. Xiang D, Konigsberger M, Wabuyele B, Hornung K, Cheney J, , 2009. Development of robust quantitative methods by near-infrared spectroscopy for rapid pharmaceutical determination of content uniformity in complex tablet matrix. Analyst (Lond) 134: 14051415.
  36. Bakeev KA, Chimenti RV, 2013. Pros and Cons of Using Correlation Versus Multivariate Algorithms for Material Identification via Handheld Spectroscopy. Available at: http://www.americanpharmaceuticalreview.com/1504-White-Papers-Application-Notes/147135-Pros-and-Cons-of-Using-Correlation-Versus-Multivariate-Algorithms-for-Material-Identification-via-Handheld-Spectroscopy/. Accessed August 30, 2013.
  37. Kovacs S, Hawes SE, Maley SN, Mosites E, Wong K, Stergachis A, , 2014. Technologies for detecting falsified and substandard drugs in low and middle-income countries. PLoS One 9: e90601.
  38. Pfizer Global Security, 2007. A Serious Threat to Patient Safety, Counterfeit Pharmaceuticals, Available at: http://www.pfizer.com/files/products/CounterfeitBrochure.pdf. Accessed May 13, 2016.
  39. Bruno C, , Hancock, Matthew P. Mullarney, 2005. X-ray microtomography of solid dosage forms. Pharm Tech. Available at: http://www.pharmtech.com/x-ray-microtomography-solid-dosage-forms-0. Accessed June 19, 2016.
  40. Schneider CA, Rasband WS, Eliceiri KW, , 2012. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9: 671675.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.16-0971
Loading
/content/journals/10.4269/ajtmh.16-0971
Loading

Data & Media loading...

  • Received : 10 Dec 2016
  • Accepted : 09 May 2017

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error