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. 2015 Feb 19;3(3):1–15. doi: 10.1007/BF02830615

Near-infrared spectral imaging for quality assurance of pharmaceutical products: Analysis of tablets to assess powder blend homogeneity

Robbe C Lyon 1,✉, David S Lester 2, E Neil Lewis 3, Eunah Lee 3, Lawrence X Yu 1, Everett H Jefferson 1, Ajaz S Hussain 4
PMCID: PMC2784046  PMID: 12916932

Abstract

The objective of this study was to evaluate near-infrared (NIR) spectroscopic imaging as a tool to assess a pharmaceutical quality assurance problem—blend uniformity in the final dosage product. A system based on array detector technology was used to rapidly collect high-contrast NIR images of furosemide tablets. By varying the mixing, 5 grades of experimental tablets containing the same amount of furosemide and microcrystalline cellulose were produced, ranging from well blended to unblended. For comparison, these tablets were also analyzed by traditional NIR spectroscopy, and both approaches were used to evaluate drug product homogeneity. NIR spectral imaging was capable of clearly differentiating between each grade of blending, both qualitatively and quantitatively. The spatial distribution of the components was based on the variation or contrast in pixel intensity, which is due to the NIR spectral contribution to each pixel. The chemical nature of each pixel could be identified by the localized spectrum associated with each pixel. Both univariate and partial least squares (PLS) images were evaluated. In the suboptimal blends, the regions of heterogeneity were obvious by visual inspection of the images. A quantitative measure of blending was determined by calculating the standard deviation of the distribution of pixel intensities in the PLS score images. The percent standard deviation increased progressively from 11% to 240% from well blended to unblended tablets. The NIR spectral imaging system provides a rapid approach for acquiring spatial and spectral information on pharmaceuticals. The technique has potential for a variety of applications in product quality assurance and could affect the control of manufacturing processes.

Key Words: NIR imaging, chemical imaging, NIR spectroscopy, blend uniformity, quality assurance

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References

  • 1.Blanco M, Coello J, Iturriaga H, Maspoch S, de la Pezuela C. Near-infrared spectroscopy in the pharmaceutical industry. Analyst. 1998;123:135R–150R. doi: 10.1039/a802531b. [DOI] [PubMed] [Google Scholar]
  • 2.Bugay DE. Characterization of the solid-state: spectroscopic techniques. Adv Drug Deliv Rev. 2001;48:43–65. doi: 10.1016/S0169-409X(01)00101-6. [DOI] [PubMed] [Google Scholar]
  • 3.Wargo DJ, Drennen JK. Near-infrared spectroscopic characterization of pharmaceutical powder blends. J Pharm Biomed Anal. 2002;14:1415–1423. doi: 10.1016/0731-7085(96)01739-6. [DOI] [PubMed] [Google Scholar]
  • 4.Hailey PA, Doherty P, Tapsell P, Oliver T, Aldridge PK. Automated system for the on-line monitoring of powder blending processes using near-infrared spectroscopy. Part I. System development and control. J Pharm Biomed Anal. 2002;14:551–559. doi: 10.1016/0731-7085(95)01674-0. [DOI] [PubMed] [Google Scholar]
  • 5.Sekulic SS, Ward HW, Brannegan DR, et al. Online monitoring of powder blend homogeneity by nearinfrared spectroscopy. Anal Chem. 2002;68:509–513. doi: 10.1021/ac950964m. [DOI] [PubMed] [Google Scholar]
  • 6.El-Hagrasy AS, Morris HR, D Amico F, Lodder RA, Drennen JK. Near-infrared spectroscopy and imaging for the monitoring of powder blend homogeneity. J Pharm Sci. 2001;90:1298–1307. doi: 10.1002/jps.1082. [DOI] [PubMed] [Google Scholar]
  • 7.Delhaye M, Dhamelincourt P. Raman microprobe and microscope with laser excitation. J Raman Spectrosc. 1975;3:33–43. doi: 10.1002/jrs.1250030105. [DOI] [Google Scholar]
  • 8.Treado PJ, Morris MD. Infrared and Raman Spectroscopic Imaging. In: Morris MD, editor. Microscopic and Spectroscopic Imaging of the Chemical State. New York, NY: Marcel Dekker; 1993. pp. 71–108. [Google Scholar]
  • 9.Harthcock MA, Atkin SC. Imaging with functional group maps using infrared microspectroscopy. Appl Spectrosc. 1988;42:449–455. doi: 10.1366/0003702884427780. [DOI] [Google Scholar]
  • 10.Krishan K, Powell JR, Hill SL. Infrared microimaging. In: Humecki HJ, editor. Practical Guide to Infrared Microspectroscopy. New York, NY: Marcel Dekker; 1995. pp. 85–110. [Google Scholar]
  • 11.Gat N. Imaging spectroscopy using tunable filters: a review. Proc SPIE-Int Soc Opt Eng. 2000;4056:50–64. [Google Scholar]
  • 12.Schaeberle MD, Morris HR, Turner JF, Treado PJ. Raman chemical imaging spectroscopy. Anal Chem. 1999;5:175A–181A. doi: 10.1021/ac990251u. [DOI] [PubMed] [Google Scholar]
  • 13.Treado PJ, Levin IW, Lewis EN. High fidelity Raman imaging spectroscopy: a rapid method using an acousto-optic tunable filter. Appl Specrosc. 1992;46:1211–1216. doi: 10.1366/0003702924123980. [DOI] [Google Scholar]
  • 14.Treado PJ, Levin IW, Lewis EN. Indium antimonide (InSb) focal plane array (FPA) detection for nearinfrared imaging microscopy. Appl Specrosc. 1994;48:607–615. doi: 10.1366/0003702944924899. [DOI] [Google Scholar]
  • 15.Tran CD, Cui Y, Smirnov S. Simultaneous multispectral imaging in the visible and near-infrared region: applications in document authentication and determination of chemical inhomogeneity of copolymers. Anal Chem. 1998;70:4701–4708. doi: 10.1021/ac980647q. [DOI] [PubMed] [Google Scholar]
  • 16.Lewis EN, Treado PJ, Reeder RC, et al. Fourier transform spectroscopic imaging using an infrared focal-plane array detector. Anal Chem. 1995;67:3377–3381. doi: 10.1021/ac00115a003. [DOI] [PubMed] [Google Scholar]
  • 17.Kidder LH, Levin IW, Lewis EN, Kleiman VD, Heilweil EJ. MCT focal-plane array detection for midinfrared FT spectroscopic imaging. Opt Lett. 1997;22:742–744. doi: 10.1364/OL.22.000742. [DOI] [PubMed] [Google Scholar]
  • 18.Lewis EN, Carroll JE, Clarke F. A near-infrared view of pharmaceutical formulation analysis. NIR News. 2001;12:16–18. doi: 10.1255/nirn.618. [DOI] [Google Scholar]
  • 19.Zugates CT, Treado PK. Raman chemical imaging of pharmaceutical content uniformity. Int J Vibr Spectrosc. 1999;2:4–4. [Google Scholar]
  • 20.Breitenbach J, Schrof W, Neumann J. Confocal Raman-spectroscopy: analytical approach to solid dispersions and mapping of drugs. Pharm Res. 1999;16:1109–1113. doi: 10.1023/A:1018956304595. [DOI] [PubMed] [Google Scholar]
  • 21.The use of stratified sampling of blend and dosage units to demonstrate adequacy of mix for powder blends. Availible at: http://www.pqri.org/datamining/imagespdfs/bua052601p r.pdf. [PubMed]

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