title: 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.
authors.affiliation: Division of Product Quality Research, Food and Drug Administration, Kensington, MD 20895, USA. lyonr@cder.fda.gov
authors.forename: Robbe C
authors.initials: RC
authors.lastname: Lyon
authors.forename: David S
authors.initials: DS
authors.lastname: Lester
authors.forename: E Neil
authors.initials: EN
authors.lastname: Lewis
authors.forename: Eunah
authors.initials: E
authors.lastname: Lee
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
authors.forename: Everett H
authors.initials: EH
authors.lastname: Jefferson
authors.forename: Ajaz S
authors.initials: AS
authors.lastname: Hussain
mesh_terms: D002482:Cellulose / Q000378:metabolism; D005665:Furosemide / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011208:Powders / Q000737:chemistry* / Q000378:metabolism; D011786:Quality Control; D012015:Reference Standards; D019265:Spectroscopy, Near-Infrared / Q000379:methods / Q000592:standards*; D013229:Stearic Acids / Q000378:metabolism; D013607:Tablets / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders; D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid; D005665:Furosemide; D002482:Cellulose