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Enhanced Quality Control in Pharmaceutical Applications by Combining Raman Spectroscopy and Machine Learning Techniques

  • J. C. Martinez
  • J. R. Guzmán-Sepúlveda
  • G. R. Bolañoz Evia
  • T. Córdova
  • R. Guzmán-Cabrera
ATPC 2016
Part of the following topical collections:
  1. Asian Thermophysical Properties Conference Papers

Abstract

In this work, we applied machine learning techniques to Raman spectra for the characterization and classification of manufactured pharmaceutical products. Our measurements were taken with commercial equipment, for accurate assessment of variations with respect to one calibrated control sample. Unlike the typical use of Raman spectroscopy in pharmaceutical applications, in our approach the principal components of the Raman spectrum are used concurrently as attributes in machine learning algorithms. This permits an efficient comparison and classification of the spectra measured from the samples under study. This also allows for accurate quality control as all relevant spectral components are considered simultaneously. We demonstrate our approach with respect to the specific case of acetaminophen, which is one of the most widely used analgesics in the market. In the experiments, commercial samples from thirteen different laboratories were analyzed and compared against a control sample. The raw data were analyzed based on an arithmetic difference between the nominal active substance and the measured values in each commercial sample. The principal component analysis was applied to the data for quantitative verification (i.e., without considering the actual concentration of the active substance) of the difference in the calibrated sample. Our results show that by following this approach adulterations in pharmaceutical compositions can be clearly identified and accurately quantified.

Keywords

Acetaminophen Machine learning Polymorph detection Principal components analysis Raman spectroscopy 

References

  1. 1.
    Organización Mundial de la Salud, La falsificación de medicamentos: una amenaza creciente. OMS 88, 241–320 (2010)Google Scholar
  2. 2.
  3. 3.
    C.S. Gautam, A. Utreja, G.L. Singal, Spurious and counterfeit drugs: a growing industry in the developing world. Postgrad. Med. J. 85, 251–256 (2009)CrossRefGoogle Scholar
  4. 4.
    S. Nitin, S. Tanushree, Generic drug industry in India: the counterfeit spin. J. Intellect. Prop. Rights 14, 236–240 (2009)Google Scholar
  5. 5.
    K. Theodore, K. Iosif, I.R. Petros, E.F. Matthew, Counterfeit or substandard antimicrobial drugs: a review of scientific evidence. J. Antimicrob. Chemother. 60, 214–236 (2007)CrossRefGoogle Scholar
  6. 6.
    A. Tariq, C. Imti, S. Helen, Substandard and counterfeit medicines: a systematic review of the literature. BMJ Open 3, 1–7 (2013)Google Scholar
  7. 7.
    P. Yashwant, Emerging techniques for polymorph detection. Int. J. Chem. Pharm. Anal. 3(1), 2–3Google Scholar
  8. 8.
    K. Wichmann, A. Klamt, Drug solubility and reaction thermodynamics. Chem. Eng. Pharm. Ind. R&D Manuf. 1, 457–476 (2010)CrossRefGoogle Scholar
  9. 9.
    J. Luyapaert, D.L. Massart, Y. Vander, Near-infrared spectroscopy applications in pharmaceutical analysis. Talanta 72, 865–883 (2007)CrossRefGoogle Scholar
  10. 10.
    S.M. Raoul, S.D. Yung, D. Volker, Z. Renato, Nanoscale chemical analysis by tip-enhanced Raman spectroscopy. Chem. Phys. 318, 131–136 (2000)Google Scholar
  11. 11.
    S.R. Goodyear, R.M. Aspden, Raman microscopy of bone, in Bone Research Protocols, ed. by M.H. Helfrich (Humana Press, Totowa, NJ, 2012), pp. 15–30Google Scholar
  12. 12.
    R.M. El-Abassy, P. Donfack, A. Materny, Visible Raman spectroscopy for the discrimination of olive oils from different vegetable oils and the detection of adulteration. J. Raman Spectrosc. 40, 1284–1289 (2009)ADSCrossRefGoogle Scholar
  13. 13.
    L. Olga, S.C. Nilam, Y.R. Chanda, W.T. Joseph, R.G. Matthew, V.D. Richard, Real-time glucose sensing by surface-enhanced Raman spectroscopy in bovine plasma facilitated by a mixed decanethiol/mercaptohexanol partition layer. Anal. Chem. 19, 6134–6139 (2005)Google Scholar
  14. 14.
    S. Ruchita, Y. Agrawal, Raman spectroscopy: recent advancements, techniques and applications. Vib. Spectrosc. 57, 163–176 (2011)CrossRefGoogle Scholar
  15. 15.
    L.M. Richard, Raman scattering, Chap. 2, in The Raman spectroscopy for chemical analysis, ed. by L.M. Richard (Wiley, Columbus, Ohio, 2000), pp. 15–30Google Scholar
  16. 16.
    S. Ewen, D. Geoffrey, Raman spectroscopy, Chap. 3, in The modern Raman spectroscopy: a practical approach, ed. by E. Smith, G. Dent (Wiley, Chichester, West Sussex, 2005), pp. 71–91Google Scholar
  17. 17.
    C.L. Haynes, A.D. McFarland, R.P. Van Duyne, Surface-enhanced Raman spectroscopy. Am. Chem. Soc. 77, 338 (2005)Google Scholar
  18. 18.
    S.Y. Lin, An overview of famotidine polymorphs: solid-state characteristics, thermodynamics, polymorphic transformation and quality control. Pharm. Res. 31, 1619–1631 (2014)CrossRefGoogle Scholar
  19. 19.
    S.Y. Lin, W.T. Cheng, The use of hot-stage microscopy and thermal micro-Raman spectroscopy in the study of phase transformation of metoclopramide HCl monohydrate. J. Raman Spectrosc. 43, 1166–1170 (2012)ADSCrossRefGoogle Scholar
  20. 20.
    T. Kojima, S. Onoue, N. Murase, F. Katoh, T. Mano, Y. Matsuda, Crystalline form information from multiwell plate salt screening by use of Raman microscopy. Pharm. Res. 23, 806–812 (2006)CrossRefGoogle Scholar
  21. 21.
    A. Heinz, M. Savolainen, T. Rades, C.J. Strachan, Quantifying ternary mixtures of different solid-state forms of indomethacin by Raman and near-infrared spectroscopy. Eur. J. Pharm. Sci. 32(3), 182–192 (2007)CrossRefGoogle Scholar
  22. 22.
    A.P. Ayala, Polymorphism in drugs investigated by low wavenumber Raman scattering. Vib. Spectrosc. 45, 112–116 (2007)CrossRefGoogle Scholar
  23. 23.
    C.M. McGoverin, T. Rades, K.C. Gordon, Recent pharmaceutical applications of Raman and terahertz spectroscopies. J. Pharm. Sci. 97, 4598–4621 (2008)CrossRefGoogle Scholar
  24. 24.
    S. Stewart, R.J. Priore, M.P. Nelson, P.J. Treado, Raman imaging. Annu. Rev. Anal. Chem. 5, 337–360 (2012)CrossRefGoogle Scholar
  25. 25.
    A. Paudel, D. Raijada, J. Rantanen, Raman spectroscopy in pharmaceutical product design. Adv. Drug Deliv. Rev. 89, 3–20 (2015)CrossRefGoogle Scholar
  26. 26.
    Y. Shen, T. Paul, E. Claire, P. Andrew, P. Nikin, Detection of low levels of amorphous lactose using H/D exchange and FT-Raman spectroscopy. Pharm. Res. 25, 2650–2656 (2008)CrossRefGoogle Scholar
  27. 27.
    Z. Huang, X. Chen, Y. Chen, J. Chen, M. Dou, S. Feng, H. Zeng, R. Chen, Raman spectroscopic characterization and differentiation of seminal plasma. J. Biomed. Opt. 16, 110501 (2011)ADSCrossRefGoogle Scholar
  28. 28.
    M. Hoehse, A. Paul, I. Gornushkin, U. Panne, Multivariate classification of pigments and inks using combined Raman spectroscopy and LIBS. Anal. Bioanal. Chem. 402, 1443–1450 (2012)CrossRefGoogle Scholar
  29. 29.
    R. Kast, R. Rabah, H. Wills, J. Poulik, G.W. Auner, M.D. Klein, Differentiation of small round blue cell tumors using Raman spectroscopy. J. Pediatr. Surg. 45, 1110–1114 (2010)CrossRefGoogle Scholar
  30. 30.
    F. Nishioka, I. Nakanishi, T. Fujiwara, K. Tomita, The crystal and molecular structure of the β-cyclodextrin inclusion complex with aspirin and salicylic acid. J. Incl. Phenom. 2, 701–714 (1984)CrossRefGoogle Scholar
  31. 31.
    J. Peng, S. Peng, A. Jiang, J. Wei, C. Li, J. Tan, Asymmetric least squares for multiple spectra baseline correction. Anal. Chim. Acta 683, 63–68 (2010)CrossRefGoogle Scholar
  32. 32.
    T. Vankeirsbilck, A. Vercauteren, W. Baeyens, F. Verport, Applications of Raman spectroscopy in pharmaceutical analysis. Trends Anal. Chem. 12, 869–877 (2002)CrossRefGoogle Scholar
  33. 33.
    W. Siegfried, H.H. Reinhard, Pharmaceutical applications of mid-IR and Raman spectroscopy. Adv. Drug Deliv. Rev. 57, 1144–1170 (2005)CrossRefGoogle Scholar
  34. 34.
    P.D. Schmitt, E.L. DeWalt, X.Y. Dow, G.J. Simpson, Rapid discrimination of polymorphic crystal forms by nonlinear optical Stokes ellipsometric microscopy. Anal. Chem. 88, 5760–5768 (2016)CrossRefGoogle Scholar
  35. 35.
    J.F. Kauffman, L.M. Batykefer, D.D. Tuschel, Raman detected differential scanning calorimetry of polymorphic transformations in acetaminophen. J. Pharm. Biomed. Anal. 48, 1310–1315 (2008)CrossRefGoogle Scholar
  36. 36.
    ChemImage™, Discrimination of acetaminophen polymorphs using Raman chemical imaging. Application Note (2010)Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • J. C. Martinez
    • 1
  • J. R. Guzmán-Sepúlveda
    • 2
  • G. R. Bolañoz Evia
    • 1
  • T. Córdova
    • 4
  • R. Guzmán-Cabrera
    • 3
  1. 1.Instituto Politécnico Nacional-Unidad Profesional Interdisciplinaria de Ingeniería Campus GuanajuatoSilao de la VictoriaMéxico
  2. 2.CREOL, The College of Optics and PhotonicsUniversity of Central FloridaOrlandoUSA
  3. 3.Universidad de Guanajuato-División de IngenieríasSalamancaMéxico
  4. 4.Universidad de Guanajuato-División de Ciencias e IngenieríasLeónMéxico

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