Analytical and Bioanalytical Chemistry

, Volume 398, Issue 1, pp 93–109 | Cite as

Practical issues of hyperspectral imaging analysis of solid dosage forms

  • José Manuel AmigoEmail author


Hyperspectral imaging techniques have widely demonstrated their usefulness in different areas of interest in pharmaceutical research during the last decade. In particular, middle infrared, near infrared, and Raman methods have gained special relevance. This rapid increase has been promoted by the capability of hyperspectral techniques to provide robust and reliable chemical and spatial information on the distribution of components in pharmaceutical solid dosage forms. Furthermore, the valuable combination of hyperspectral imaging devices with adequate data processing techniques offers the perfect landscape for developing new methods for scanning and analyzing surfaces. Nevertheless, the instrumentation and subsequent data analysis are not exempt from issues that must be thoughtfully considered. This paper describes and discusses the main advantages and drawbacks of the measurements and data analysis of hyperspectral imaging techniques in the development of solid dosage forms.


Hyperspectral imaging Near infrared Middle infrared Raman Pharmaceutical research Solid dosage forms Tablets Process analytical technologies 



J.M.A. would like to thank Carsten Ravn from Lundbeck and Rasmus Bro from the Department of Food Sciences, Quality and Technology of the University of Copenhagen for their comments and their valuable help. The author specially thanks Nuno Ratola from the Departamento de Engenharia Química da Universidade do Porto (Portugal) for his support with language correction.


  1. 1.
    Aulton ME (2007) Aulton's pharmaceutics: the design and manufacture of medicines, 3rd edn. Churchill Livingstone, OxfordGoogle Scholar
  2. 2.
    Ravn C (2009) Near-infrared chemical imaging in formulation development of solid dosage forms. PhD thesis, University of CopenhagenGoogle Scholar
  3. 3.
    The European Pharmacopeia, 6th edition (6.2). 07 Dosage Forms: Tablets. European Directorate for the Quality of Medicines & Healthcare, EDQM, 2008Google Scholar
  4. 4.
    U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for Industry: Powder Blends and Finished Dosage Units – Stratified In-Process Dosage Units Sampling and Assessment. Draft Guidance. October, 2003Google Scholar
  5. 5.
    Amigo JM, Cruz J, Bautista M, Maspoch S, Coello J, Blanco M (2008) Trends Anal Chem 27:696–713CrossRefGoogle Scholar
  6. 6.
    Gendrin C, Roggo Y, Collet C (2008) J Pharm Biomed Anal 48:533–553CrossRefGoogle Scholar
  7. 7.
    Roggo Y, Edmond A, Chalus P, Ulmschneider M (2005) Anal Chim Acta 535:79–87CrossRefGoogle Scholar
  8. 8.
    Clark D, Henson MJ, LaPlant F, Sasic S, Zhang L (2007) In: Pivonka DE, Chalmers JM, Griffiths PR (eds) The handbook of vibrational spectroscopy, applications in life, pharmaceutical and natural sciences, pharmaceutical applications. Wiley, Hoboken, pp 1–27Google Scholar
  9. 9.
    Gowen AA, O'Donnell CP, Cullen PJ, Bell SEJ (2008) Eur J Pharm Biopharm 69:10–22CrossRefGoogle Scholar
  10. 10.
    Hammond SV, Clarke FC (2002) In: Chalmers JM, Griffiths PR (eds) The handbook of vibrational spectroscopy, sampling techniques, microscopy. Wiley, Hoboken, pp 1405–1431Google Scholar
  11. 11.
    Lewis EN, Dubois J, Kidder LH, Haber KS (2007) In: Grahn H, Geladi P (eds) Techniques and applications of hyperspectral image analysis. Wiley, Hoboken, pp 335–361CrossRefGoogle Scholar
  12. 12.
    Lewis EN, Schoppelrei J, Lee E, Kidder LH (2005) Process analytical technology. Blackwell, CambridgeGoogle Scholar
  13. 13.
    Reich G (2005) Adv Drug Delivery Rev 57:1109–1143CrossRefGoogle Scholar
  14. 14.
    Zhang L, Henson MJ, Sekulic SS (2005) Anal Chim Acta 54:262–278CrossRefGoogle Scholar
  15. 15.
    Burger JE (2006) Department of Biomass Technology and Chemistry. Swedish University of Agriculutral Sciences, UmeåGoogle Scholar
  16. 16.
    Clark D, Sasic S (2006) Cytometry Part A 69A:815–824CrossRefGoogle Scholar
  17. 17.
    Fernandez Pierna JA, Baeten V, Dardenne P, Dubois J, Lewis EN, Burger J (2009) Comprehensive chemometrics. Chemical and biochemical data analysis, Elsevier, AmsterdamGoogle Scholar
  18. 18.
    Liu Z, Yu H, MacGregor JF (2007) J Chemom 21:89–95CrossRefGoogle Scholar
  19. 19.
    Sasic S, Clark DA (2006) Appl Spectrosc 60:494–502CrossRefGoogle Scholar
  20. 20.
    Katrasnik J, Bürmen M, Pernus F, Likar B (2010) Chemom Intell Lab Syst 101:23–29. doi: 10.1016/j.chemolab.2009.11.012 CrossRefGoogle Scholar
  21. 21.
    Levin IW, Bhargava R (2005) Annu Rev Phys Chem 56:429–474CrossRefGoogle Scholar
  22. 22.
    De Juan A, Maeder M, Hancewicz T, Duponchel L, Tauler R (2009) In: Salzer R, Siesler HW (eds) Infrared and Raman spectroscopic imaging. Wiley-VCH, Weinheim, pp 65–112CrossRefGoogle Scholar
  23. 23.
    Hammond SV (1998) Eur Pharm Rev 3:47–51Google Scholar
  24. 24.
    El-Hagrasy AS, Morris HR, D'Amico F, Lodder RA, Drennen JK (2001) J Pharm Sci 90:1298–1307CrossRefGoogle Scholar
  25. 25.
    Chan KLA, Kazarian SG (2003) Appl Spectrosc 57:381–389CrossRefGoogle Scholar
  26. 26.
    Chan KLA, Hammond SV, Kazarian SG (2003) Anal Chem 75:2140–2146CrossRefGoogle Scholar
  27. 27.
    Chan KLA, Kazarian SG (2004) Mol Pharm 1:331–335CrossRefGoogle Scholar
  28. 28.
    Chan KLA, Kazarian SG (2006) Lab Chip 6:864–870CrossRefGoogle Scholar
  29. 29.
    Kazarian SG, Kong KWT, Bajomo M, Van der Weerd J, Chan KLA (2005) Food Bioprod Process 83:127–135CrossRefGoogle Scholar
  30. 30.
    van der Weerd J, Kazarian SG (2004) J Control Release 98:295–305CrossRefGoogle Scholar
  31. 31.
    van der Weerd J, Kazarian SG (2004) Appl Spectrosc 58:1413–1419CrossRefGoogle Scholar
  32. 32.
    Van der Weerd J, Kazarian SG (2005) J Pharm Sci 94:2096–2109CrossRefGoogle Scholar
  33. 33.
    Cairós C, Amigo JM, Watt R, Coello J, Maspoch S (2009) Talanta 79:657–664CrossRefGoogle Scholar
  34. 34.
    Hamilton SJ, Lodder RA (2002) Proc SPIE 4626:136–147CrossRefGoogle Scholar
  35. 35.
    Lee E, Huang WX, Chen P, Lewis EN, Vivilecchia RV (2006) Spectroscopy 21:24–32Google Scholar
  36. 36.
    Clarke FC, Hammond SV, Jee RD, Moffat AC (2002) Appl Spectrosc 56:1475–1483CrossRefGoogle Scholar
  37. 37.
    Hudak SJ, Haber KS, Sando G, Kidder LH, Lewis EN (2007) NIR News 18:6–8CrossRefGoogle Scholar
  38. 38.
    LaPlant F (2004) Am Pharm Rev 7:16–24Google Scholar
  39. 39.
    Everall NJ, Priestnall IM, Clarke F, Jayes L, Poulter G, Coombs D, George MW (2009) Appl Spectrosc 63:313–320CrossRefGoogle Scholar
  40. 40.
    Kazarian SG, Chan KLA (2006) Prog Colloid Polym Sci 132:1–6CrossRefGoogle Scholar
  41. 41.
    Russ JC (2005) Image analysis of food microstructure. CRC, Boca RatonGoogle Scholar
  42. 42.
    Wray P, Chan KLA, Kimber J, Kazarian SG (2008) J Pharm Sci 97:4269–4277CrossRefGoogle Scholar
  43. 43.
    Lewis EN, Lee E, Kidder LH (2004) Microsc Today 8–12Google Scholar
  44. 44.
    Sasic S (2008) Anal Chim Acta 611:73–79CrossRefGoogle Scholar
  45. 45.
    Onat BM, Carver G, Itzler M (2008) Proc. of SPIE, vol 7310, pp 731004–1/11Google Scholar
  46. 46.
    Burger J, Geladi P (2006) J Chemom 20:106–119CrossRefGoogle Scholar
  47. 47.
    Gendrin C, Roggo Y, Collet C (2007) Talanta 73:733–741CrossRefGoogle Scholar
  48. 48.
    de Juan A, Tauler R, Dyson R, Marcolli C, Rault M, Maeder M (2004) Trends Anal Chem 23:70–79CrossRefGoogle Scholar
  49. 49.
    Amigo JM, Ravn C (2009) Eur J Pharm Sci 37:76–82CrossRefGoogle Scholar
  50. 50.
    Furukawa T, Sato H, Shinzawa H, Noda I, Ochiai S (2007) Anal Sci 23:871–876CrossRefGoogle Scholar
  51. 51.
    Puchert T, Lochmann D, Menezes JC, Reich G (2010) J Pharm Biomed Anal 51:138–145CrossRefGoogle Scholar
  52. 52.
    Elkhider N, Chan KLA, Kazarian SG (2007) J Pharm Sci 96:351–360CrossRefGoogle Scholar
  53. 53.
    Lyon RC, Lester DS, Lewis EN, Lee E, Yu LX, Jefferson EH, Hussain AS (2002) AAPS PharmSciTech 3:1–17CrossRefGoogle Scholar
  54. 54.
    Sasic S, Clark DA, Mitchell JC, Snowden MJ (2005) Analyst 130:1530–1536CrossRefGoogle Scholar
  55. 55.
    Sasic S, Clark DA, Mitchell JC, Snowden MJ (2004) Analyst 129:1001–1007CrossRefGoogle Scholar
  56. 56.
    Dubois J, Wolff JC, Warrack JK, Schoppelrei J, Lewis EN (2007) Spectroscopy 22:40Google Scholar
  57. 57.
    Rodionova OY, Houmoller LP, Pomerantsev AL, Geladi P, Burger J, Dorofeyev VL, Arzamastsev AP (2005) Anal Chim Acta 549:151–158CrossRefGoogle Scholar
  58. 58.
    de Juan A, Maeder M, Hancewicz T, Tauler R (2005) Chemom Intell Lab Syst 77:64–74Google Scholar
  59. 59.
    de Juan A, Maeder M, Hancewicz T, Tauler R (2008) J Chemom 22:291–298CrossRefGoogle Scholar
  60. 60.
    Realpe A, Velazquez C (2003) Powder Technol 134:193–200CrossRefGoogle Scholar
  61. 61.
    Ravn C, Bro R, Skibsted E (2008) J Pharm Biomed Anal 48:554–561CrossRefGoogle Scholar
  62. 62.
    Burger J, Geladi P (2006) Analyst 131:1152–1160CrossRefGoogle Scholar
  63. 63.
    Kolomiets O, Hoffmann U, Geladi P, Siesler HW (2008) Appl Spectrosc 62:1200–1208CrossRefGoogle Scholar
  64. 64.
    Awa K, Okumura T, Shinzawa H, Otsuka M, Ozaki Y (2008) Anal Chim Acta 619:81–86CrossRefGoogle Scholar
  65. 65.
    Cruz J, Bautista M, Amigo JM, Blanco M (2009) Talanta 80:473–478CrossRefGoogle Scholar
  66. 66.
    de Juan A, Tauler R (2006) Crit Rev Anal Chem 36:163–176CrossRefGoogle Scholar
  67. 67.
    Gendrin C, Roggo Y, Collet C (2008) J Near Infrared Spectrosc 16:151–157CrossRefGoogle Scholar
  68. 68.
    Lopes MB, Wolff JC (2009) Anal Chim Acta 633:149–155CrossRefGoogle Scholar
  69. 69.
    Lin WQ, Jiang JH, Yang HF, Ozaki Y, Shen GL, Yu RQ (2006) Anal Chem 78:6003–6011CrossRefGoogle Scholar
  70. 70.
    Amigo JM, Ravn C, Gallagher NB, Bro R (2009) Int J Pharm 373:179–182CrossRefGoogle Scholar
  71. 71.
    Jovanovic N, Gerich A, Bouchard A, Jiskoot W (2006) Pharm Res 23:2002–2013CrossRefGoogle Scholar
  72. 72.
    Lopes MB, Wolff JC, Bioucas-Dias JM, Figueiredo MAT (2009) Anal Chim Acta 641:46–51CrossRefGoogle Scholar
  73. 73.
    Weiyong L, Woldu A, Kelly R (2008) Int J Pharm 350:369–373CrossRefGoogle Scholar
  74. 74.
    Li WY, Woldu A, Kelly R, McCool J, Bruce R, Rasmussen H, Cunningham J, Winstead D (2008) Int J Pharm 350:369–373CrossRefGoogle Scholar
  75. 75.
    Otsu N (1979) IEEE Trans Syst Man Cybern 9:62–66CrossRefGoogle Scholar
  76. 76.
    Ma H, Anderson CA (2007) J Near Infrared Spectrosc 15:137–151CrossRefGoogle Scholar
  77. 77.
    Lewis EN, Kidder LH, Lee E (2006) Innov Pharm Technol 17Google Scholar
  78. 78.
    Gosselin R, Duchesne C, Rodrigue D (2008) Powder Technol 183:177–188CrossRefGoogle Scholar
  79. 79.
    Hilden LR, Pommier CJ, Badawy SIF, Friedman EA (2008) Int J Pharm 353:283–290Google Scholar
  80. 80.
    Hamad ML, Ellison CD, Khan MA, Lyon RC (2007) J Pharm Sci 96:3390–3401CrossRefGoogle Scholar
  81. 81.
    Svensson O, Abrahamsson K, Engelbrektsson J, Nicholas M, Wikstrom H, Josefson M (2006) Chemom Intell Lab Syst 84:3–8CrossRefGoogle Scholar
  82. 82.
    Clarke FC, Jamieson MJ, Clark DA, Hammond SV, Jee RD, Moffat AC (2001) Anal Chem 73:2213–2220CrossRefGoogle Scholar
  83. 83.
    Gupper A, Wilhelm P, Schmied M, Kazarian SG, Chan KLA, Reussner J (2002) Appl Spectrosc 56:1515–1523CrossRefGoogle Scholar
  84. 84.
    Hamilton SJ, Lowell AE, Lodder RA (2002) J Biomed Opt 7:561–570CrossRefGoogle Scholar
  85. 85.
    Kazarian SG, Chan KLA (2003) Macromolecules 36:9866–9872CrossRefGoogle Scholar
  86. 86.
    Lewis EN, Carroll JD, Clarke FM (2001) NIR News 12:16Google Scholar
  87. 87.
    Lyon RC, Jefferson EH, Ellison CD, Buhse LF, Spencer JA, Nasr MM, Hussain AS (2003) Am Pharm Rev 6:62–70Google Scholar
  88. 88.
    Reich G (2002) Pharm Ind 64:870–874Google Scholar
  89. 89.
  90. 90.
    Bellamy LJ, Nordon A, Littlejohn D (2008) Int J Pharm 361:87–91CrossRefGoogle Scholar
  91. 91.
    Shah RB, Tawakkul MA, Khan MA (2007) J Pharm Sci 96:1356–1365CrossRefGoogle Scholar
  92. 92.
    Chan KLA, Kazarian SG (2005) J Comb Chem 7:185–189CrossRefGoogle Scholar
  93. 93.
    Chan KLA, Kazarian SG, Vassou D, Gionis V, Chryssikos GD (2007) Vib Spectrosc 43:221–226CrossRefGoogle Scholar
  94. 94.
    Kazarian SG (2007) Anal Bioanal Chem 388:529–532CrossRefGoogle Scholar
  95. 95.
    Makein LJ, Kidder LH, Lewis EN, Valleri M (2008) NIR News 7:11–15CrossRefGoogle Scholar
  96. 96.
    Duponchel L, Milanfar P, Ruckebusch C, Huvenne JP (2008) Anal Chim Acta 607:168–175CrossRefGoogle Scholar
  97. 97.
    Chan KLA, Fleming OS, Kazarian SG, Vassou D, Chryssikos GD, Gionis V (2004) J Raman Spectrosc 35:353–359CrossRefGoogle Scholar
  98. 98.
    Belu A, Mahoney C, Wormuth K (2008) J Control Release 126:111–121CrossRefGoogle Scholar
  99. 99.
    BurgerMetrics (2008) BurgerMetrics JIMI. Accessed Jan 2010
  100. 100.
    Eigenvector Research (2010) Eigenvector Research, Inc. Accessed Jan 2010
  101. 101.
    UmBio (2010) Welcome to UmBio AB. Accessed Apr 2010
  102. 102.
    McMaster University (2000–2010) MACCMIA-software for multivariate image analysis | McMaster Advanced Control Consortium. Accessed Apr 2010
  103. 103.
    The MathWorks (1994–2010) MathWorks-MATLAB and Simulink for Technical Computing. Accessed Jan 2010
  104. 104.
    Geeknet (2010) matlabhyperspec. Accessed Jan 2010
  105. 105.
    Rigby SP, Van der Walle CF, Raistrick JH (2004) J Control Release 96:97–100CrossRefGoogle Scholar
  106. 106.
    Shen YC, Taday PF (2008) IEEE J Sel Top Quantum Electron 14:407–415CrossRefGoogle Scholar
  107. 107.
    Wallace VP, Taday PF, Fitzgerald AJ, Woodward RM, Cluff J, Pye RJ, Arnone DD (2004) Faraday Discuss 126:255–263CrossRefGoogle Scholar
  108. 108.
    Zeitler JA, Taday PF, Newnham DA, Pepper M, Gordon KC, Rades T (2007) J Pharm Pharmacol 59:209–223CrossRefGoogle Scholar
  109. 109.
    Ho L, Muller R, Romer M, Gordon KC, Heinamaki J, Kleinebudde P, Pepper M, Rades T, Shen YC, Strachan CJ, Taday PF, Zeitler JA (2007) J Control Release 119:253–261CrossRefGoogle Scholar
  110. 110.
    Maurer L, Leuenberger H (2009) Int J Pharm 370:8–16CrossRefGoogle Scholar
  111. 111.
    Palermo R, Cogdill RP, Short SM, Drennen JK, Taday PF (2008) J Pharm Biomed Anal 46:36–44CrossRefGoogle Scholar
  112. 112.
    Clarke F (2004) Vib Spectrosc 34:25–35CrossRefGoogle Scholar
  113. 113.
    Koehler F, Lee E, Kidder LH, Lewis EN (2002) Spectrosc Eur 14:12–19Google Scholar
  114. 114.
    Lewis EN, Kidder LH, Lee E (2005) NIR News 16:2–4Google Scholar
  115. 115.
    Lewis EN, Schoppelrei J, Lee E (2004) Spectroscopy 19Google Scholar
  116. 116.
    Westenberger BJ, Ellison CD, Fussner AS, Jenney S, Kolinski TG, Lipe TG, Lyon RC, Moore TW, Revelle LK, Smith AP, Spencer JA, Story KD, Toler DY, Wokovich AM, Buhse LF (2005) Int J Pharm 306:56–70CrossRefGoogle Scholar
  117. 117.
    Henson MJ, Zhang L (2006) Appl Spectrosc 60:1247–1255CrossRefGoogle Scholar
  118. 118.
    Sasic S (2007) Appl Spectrosc 61:239–250CrossRefGoogle Scholar
  119. 119.
    Sasic S (2007) Pharm Res 24:58–65CrossRefGoogle Scholar
  120. 120.
    Sasic S, Clark DA, Mitchell JC, Snowden MJ (2005) Appl Spectrosc 59:630–638CrossRefGoogle Scholar
  121. 121.
    Sasic S, Morimoto M, Otsuka M, Ozaki Y (2005) Vib Spectrosc 37:217–224CrossRefGoogle Scholar
  122. 122.
    Vajna B, Farkas I, Szabo A, Zsigmond Z, Marosi G (2010) J Pharm Biomed Anal 51:30–38CrossRefGoogle Scholar
  123. 123.
    Chan KLA, Elkhider N, Kazarian SG (2005) Chem Eng Res Des 83:1303–1310CrossRefGoogle Scholar
  124. 124.
    Chan KLA, Kazarian SG (2006) Analyst 131:126–131CrossRefGoogle Scholar
  125. 125.
    Kazarian SG, van der Weerd J (2008) Pharm Res 25:853–860CrossRefGoogle Scholar
  126. 126.
    Roggo Y, Jent N, Edmond A, Chalus P, Ulmschneider M (2005) Eur J Pharm Biopharm 61:100–110CrossRefGoogle Scholar
  127. 127.
    Grahn H, Geladi P (2007) Techniques and applications of hyperspectral image analysis. Wiley, HobokenCrossRefGoogle Scholar
  128. 128.
    Gosselin R, Rodrigue D, Gonzalez-Nunez R, Duchesne C (2009) Ind Eng Chem Res 48:3033–3042CrossRefGoogle Scholar
  129. 129.
    Ma H, Anderson CA (2008) J Pharm Sci 97:369–373CrossRefGoogle Scholar
  130. 130.
    Zidan AS, Sammour OA, Hammad MA, Megrab NA, Habib MJ, Khan MA (2008) J Microencapsulation 25:145–153CrossRefGoogle Scholar
  131. 131.
    Chan KLA, Kazarian SG (2004) Vib Spectrosc 35:45–49CrossRefGoogle Scholar
  132. 132.
    van der Weerd J, Chan KLA, Kazarian SG (2004) Vib Spectrosc 35:9–13CrossRefGoogle Scholar
  133. 133.
    Gendrin C, Roggo Y, Spiegel C, Collet C (2008) Eur J Pharm Biopharm 68:828–837CrossRefGoogle Scholar
  134. 134.
    Ellison CD, Ennis BJ, Hamad ML, Lyon RC (2008) J Pharm Biomed Anal 48:1–7CrossRefGoogle Scholar
  135. 135.
    Lopes MB, Wolff JC, Bioucas-Dias JM, Figueiredo MAT (2010) Anal Chem 82:1462–1469CrossRefGoogle Scholar
  136. 136.
    Ricci C, Eliasson C, Macleod NA, Newton PN, Matousek P, Kazarian SG (2007) Anal Bioanal Chem 389:1525–1532CrossRefGoogle Scholar
  137. 137.
    Ricci C, Nyadong L, Fernandez FM, Newton PN, Kazarian SG (2007) Anal Bioanal Chem 387:551–559CrossRefGoogle Scholar
  138. 138.
    Chan KLA, Kazarian SG (2006) J Comb Chem 8:26–31CrossRefGoogle Scholar
  139. 139.
    Fleming OS, Chan KLA, Kazarian SG (2004) Vib Spectrosc 35:3–7CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Food Science Quality and Technology, Faculty of Life SciencesUniversity of CopenhagenFrederiksberg CDenmark

Personalised recommendations