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AAPS PharmSciTech. 2002 September; 3(3): 1–15.
Published online 2015 February 19. doi:  10.1007/BF02830615
PMCID: PMC2784046

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

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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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. [PubMed] [Cross Ref]
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. [PubMed] [Cross Ref]
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. [PubMed] [Cross Ref]
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. [PubMed] [Cross Ref]
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. [PubMed] [Cross Ref]
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. [PubMed] [Cross Ref]
7. Delhaye M, Dhamelincourt P. Raman microprobe and microscope with laser excitation. J Raman Spectrosc. 1975;3:33–43. doi: 10.1002/jrs.1250030105. [Cross Ref]
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.
9. Harthcock MA, Atkin SC. Imaging with functional group maps using infrared microspectroscopy. Appl Spectrosc. 1988;42:449–455. doi: 10.1366/0003702884427780. [Cross Ref]
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.
11. Gat N. Imaging spectroscopy using tunable filters: a review. Proc SPIE-Int Soc Opt Eng. 2000;4056:50–64.
12. Schaeberle MD, Morris HR, Turner JF, Treado PJ. Raman chemical imaging spectroscopy. Anal Chem. 1999;5:175A–181A. doi: 10.1021/ac990251u. [PubMed] [Cross Ref]
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. [Cross Ref]
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. [Cross Ref]
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. [PubMed] [Cross Ref]
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. [PubMed] [Cross Ref]
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. [PubMed] [Cross Ref]
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. [Cross Ref]
19. Zugates CT, Treado PK. Raman chemical imaging of pharmaceutical content uniformity. Int J Vibr Spectrosc. 1999;2:4–4.
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. [PubMed] [Cross Ref]
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]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists