Analytical and Bioanalytical Chemistry

, Volume 405, Issue 29, pp 9401–9409 | Cite as

Application of a newly developed portable NIR imaging device to monitor the dissolution process of tablets

  • Daitaro Ishikawa
  • Kodai Murayama
  • Kimie Awa
  • Takuma Genkawa
  • Makoto Komiyama
  • Sergei G. Kazarian
  • Yukihiro OzakiEmail author
Research Paper


We have recently developed a novel portable NIR imaging device (D-NIRs), which has a high speed and high wavelength resolution. This NIR imaging approach has been developed by utilizing D-NIRs for studying the dissolution of a model tablet containing 20 % ascorbic acid (AsA) as an active pharmaceutical ingredient and 80 % hydroxypropyl methylcellulose, where the tablet is sealed by a special cell. Diffuse reflectance NIR spectra in the 1,000 to 1,600 nm region were measured during the dissolution of the tablet. A unique band at around 1,361 nm of AsA was identified by the second derivative spectra of tablet and used for AsA distribution NIR imaging. Two-dimensional change of AsA concentration of the tablet due to water penetration is clearly shown by using the band-based image at 1,361 nm in NIR spectra obtained with high speed. Moreover, it is significantly enhanced by using the intensity ratio of two bands at 1,361 and 1,354 nm corresponding to AsA and water absorption, respectively, showing the dissolution process. The imaging results suggest that the amount of AsA in the imaged area decreases with increasing water penetration. The proposed NIR imaging approach using the intensity of a specific band or the ratio of two bands combined with the developed portable NIR imaging instrument, is a potentially useful practical way to evaluate the tablet at every moment during dissolution and to monitor the concentration distribution of each drug component in the tablet.


Visible photo and NIR image for tablet dissolution obtained by using a newly developed portable NIR imaging device: D-NIRs


Single wavelength-based image Dissolution process monitoring NIR imaging Pharmaceutical application Portable spectrometer Ratio-based image 



The study was supported by the “Innovation Promotion Program” of the New Energy and Industrial Technology Development Organization (NEDO), Ministry of Economy, Trade and Industry, Japan.


  1. 1.
    Bakeev KA (2005) Process analytical technology—spectroscopic tools and implementation strategies for the chemical and pharmaceutical industries. Blackwell, LondonCrossRefGoogle Scholar
  2. 2.
    Hinz CD (2006) Process analytical technologies in the pharmaceutical industry the FDA's PAT initiative. Anal Bioanal Chem 384:1036–1042CrossRefGoogle Scholar
  3. 3.
    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (2009) ICH Harmonised Tripartite Guideline Pharmaceutical Development Q8 (R2)Google Scholar
  4. 4.
    Rathore SA, Bhambure R, Ghare V (2010) Process analytical technology (PAT) for biopharmaceutical products. Anal Bioanal Chem 398:137–154CrossRefGoogle Scholar
  5. 5.
    Ozaki Y (2012) Near-infrared spectroscopy—its versatility in analytical chemistry. Anal Sci 28:545–562CrossRefGoogle Scholar
  6. 6.
    Trafford AD, Jee RD, Moffat AC, Graham P (1999) A rapid quantitative assay of intact paracetamol tablets by reflectance near-infrared spectroscopy. Analyst 124:163–167CrossRefGoogle Scholar
  7. 7.
    Andersson M, Folestad S, Gottfries J, Johansson MO, Josefson M, Wahlund KG (2000) Quantitative analysis of film coating in a fluidized bed process by in-line NIR spectrometry and multivariate batch calibration. Anal Chem 2099–2108Google Scholar
  8. 8.
    Rantanen J, Räsänen E, Tenhunen J, Lansakosli M, Mannermaa JP, Yliruusi J (2000) In-line moisture measurement during granulation with a four-wavelength near infrared sensor: an evaluation of particle size and binder effect. Eur J Pharm Biopharm 50:271–276CrossRefGoogle Scholar
  9. 9.
    Ufret C, Morris K (2001) Modeling of powder blending using on-line near infrared measurements. Drug Dev Ind Pharm 27:719–729CrossRefGoogle Scholar
  10. 10.
    Li W, Worosila GD, Wang W, Mascaro T (2005) Determination of polymorphconversion of an active pharmaceutical ingredient in wet granulation using NIR calibration models generated from the premix blends. J Pharm Sci 94:2800–2806CrossRefGoogle Scholar
  11. 11.
    Roggo Y, Chalus P, Manurer L, Martinez CL, Edmond A, Jent N (2007) A review of near infrared spectroscopy and chemometrics in pharmaceutical technology. J Pharm Biomed Anal 44(3):683–700CrossRefGoogle Scholar
  12. 12.
    Kogermann K, Aaltonen J, Strachan CJ, Pollanen K, Heinamaki J, Yliruusi J, Rantanen J (2008) Establishing quantitative in-line analysis of multiple solid-state transformations during dehydration. J Pharm Sci 97:4983–4999CrossRefGoogle Scholar
  13. 13.
    Siesler HW, Ozaki Y, Kawata S, Heise HM (2002) Near-infrared spectroscopy. Wiley, WeinheimGoogle Scholar
  14. 14.
    Ozaki Y, Morita S (2009) Encyclopedia of applied spectroscopy. Wiley, WeinheimGoogle Scholar
  15. 15.
    Komiyama M, Sanpei Y, Miura A, Sakakibara K, Yakihara T, Fujita T, Kobayashi S, Oka S, Akasaka Y (2003) US Patent 6,552,325 B1Google Scholar
  16. 16.
    Murayama K, Genkawa T, Ishikawa D, Komiyama M, Ozaki Y (2013) A polychromator-type near-infrared spectrometer with a high-sensitivity and high-resolution photodiode array detector for pharmaceutical process monitoring on the millisecond time scale. Rev Sci Instrum 84:023104CrossRefGoogle Scholar
  17. 17.
    Bettini R, Catellani PL, Santi P, Massimo G, Peppas PN, Colombo P (2001) Translocation of drug particles in HPMC matrix gel layer: effect of drug solubility and influence on release rate. J Control Release 70:383–391CrossRefGoogle Scholar
  18. 18.
    Gao P, Meury RH (1996) Swelling of hydroxypropyl methylcellulosematrix tablets. 1. Characterization of swelling using a novel optical imaging method. J Pharm Sci 85:725–731CrossRefGoogle Scholar
  19. 19.
    Kimber JA, Kazarian SG, Štěpánek F (2013) Formulation design space analysis for drug release from swelling polymer tablets. Powder Technol 236:179–187CrossRefGoogle Scholar
  20. 20.
    Van der Weerd J, Kazarian SG (2004) Combined approach of FTIR imaging and conventional dissolution tests applied to drug release. J Control Release 98:295–305CrossRefGoogle Scholar
  21. 21.
    Kazarian SG, Van der Weerd J (2008) Simultaneous FTIR spectroscopic imaging and visible photography to monitor tablet dissolution and drug release. Pharm Res 25(4):853–860CrossRefGoogle Scholar
  22. 22.
    Hattori Y, Otsuka M (2011) NIR spectroscopic study of the dissolution process in pharmaceutical tablets. Vib Spectrosc 57(2):275–281Google Scholar
  23. 23.
    Morita S, Shinzawa H, Noda I, Ozaki Y (2006) Perturbation-correlation moving-window two-dimensional correlation spectroscopy. Appl Spectrosc 60:398–406CrossRefGoogle Scholar
  24. 24.
    Šašić S, Ozaki Y (2009) Raman, infrared, and near-infrared chemical imaging. Wiley, New YorkGoogle Scholar
  25. 25.
    Lewis NE, Schoppelrei J, Lee E (2004) Near-infrared chemical imaging and the PAT initiative—NIR-CI adds a completely new dimension to conventional NIR spectroscopy. Spectroscopy 19(4):28–34Google Scholar
  26. 26.
    EL-Hagrasy AS, Morris HR, D’amico F, Lodder RA, Dernnen JK III (2001) Near-infrared spectroscopy and imaging for the monitoring of powder blend homogeneity. J Pharm Sci 90(9):1298–1307CrossRefGoogle Scholar
  27. 27.
    Amigo JM, Ravn C (2009) Direct quantification and distribution assessment of major and minor component in pharmaceutical tablets by NIR-chemical imaging. Eur J Pharm Sci 37(2):76–82CrossRefGoogle Scholar
  28. 28.
    Lewis EN, Carroll JE, Clarke FM (2001) A near-infrared view of pharmaceutical formulation analysis. NIR News 12(3):16–18CrossRefGoogle Scholar
  29. 29.
    Awa K, Okumura T, Shinzawa H, Otsuka M, Ozaki Y (2008) Self-modeling curve resolution (SMCR) analysis of near-infrared (NIR) imaging data of pharmaceutical tablets. Anal Chim Acta 619:81–86CrossRefGoogle Scholar
  30. 30.
    Ishikawa D, Murayama K, Genkawa T, Awa K, Komiyama M, Ozaki Y (2012) Development of compact near infrared imaging device with high-speed and portability for pharmaceutical process monitoring. NIR News 23(8):14–17CrossRefGoogle Scholar
  31. 31.
    Griffiths PR, Olinger MJ (2002) In: Chalmers JM, Griffiths PR (eds) Handbook of vibrational spectroscopy, vol 1. Wiley, New YorkGoogle Scholar
  32. 32.
    Savitzky A, Golay MJE (1964) Smoothing and differentiation of data by simplified least squares procedures. Anal Chem 36(8):1627–1639CrossRefGoogle Scholar
  33. 33.
    Kasemsumran Y, Du P, Murayama K, Huehne M, Ozaki Y (2004) Near-infrared spectroscopic determination of human serum albumin, γ-globulin, and glucose in a control serum solution with searching combination moving window partial least squares. Anal Chim Acta 512:223–230CrossRefGoogle Scholar
  34. 34.
    Sahoo S, Kanti C, Mishra CS, Naik S (2011) Analytical characterization of a gelling biodegradable polymer. Drug Invention Today 3(6):78–82Google Scholar
  35. 35.
    Pérez-Ramos DJ, Findlay PW, Peck G, Morris RK (2005) Quantitative analysis of film coating in a pan coater based on in-line sensor measurements. AAPS Pharma Sci Tech 6(1):127–136CrossRefGoogle Scholar
  36. 36.
    Lui H, Xiang BR, Qu LB (2006) Structure analysis of ascorbic acid using near-infrared spectroscopy and generalized two-dimensional correlation spectroscopy. Molecular Structure 794:12–17CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Daitaro Ishikawa
    • 1
  • Kodai Murayama
    • 2
  • Kimie Awa
    • 3
  • Takuma Genkawa
    • 4
  • Makoto Komiyama
    • 2
  • Sergei G. Kazarian
    • 5
  • Yukihiro Ozaki
    • 1
    Email author
  1. 1.School of Science and Technology, Kwansei Gakuin UniversitySandaJapan
  2. 2.Yokogawa Electric CorporationMusashinoJapan
  3. 3.Dainippon Sumitomo Pharma Co., LtdOsakaJapan
  4. 4.Faculty of Life and Environmental SciencesUniversity of TsukubaTsukubaJapan
  5. 5.Department of Chemical EngineeringImperial College LondonLondonUK

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