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.

Application of Monte Carlo Simulation-Based Photon Migration for Enhanced Understanding of Near-Infrared (NIR) Diffuse Reflectance. Part II: Photon Radial Diffusion in NIR Chemical Images

“…According to Eqs. (1)(2)(3) in Part I, 12 a larger anisotropy factor leads to a larger scattering coefficient and smaller step size. Thus, the anisotropy factor of 0.9 used in the study was believed to be too large.…”

NIR Imaging Applications in the Pharmaceutical Industry

“…In contrast to blend uniformity of powders, tablets can be analyzed as such, which avoids some of the sample integrity issues related to powders, although representative sampling of tablets (for instance, of a commercial batch) could be difficult as well. To assess blend uniformity in tablets, experimental tablets are often designed to deliberately vary the uniformity of the components by using different mixing times during the blend process [14] or varying API and excipient properties such as particle size. Using this approach, a number of objectives can be studied such as the impact of nonuniformity of specific ingredients, comparison of blend uniformity of commercial products [14,21], and the impact on uniformity caused by the tabletting process itself (Figure 11.10).…”

“…To assess blend uniformity in tablets, experimental tablets are often designed to deliberately vary the uniformity of the components by using different mixing times during the blend process [14] or varying API and excipient properties such as particle size. Using this approach, a number of objectives can be studied such as the impact of nonuniformity of specific ingredients, comparison of blend uniformity of commercial products [14,21], and the impact on uniformity caused by the tabletting process itself (Figure 11.10). The imaging approach should be chosen to achieve as much discriminating power as possible between the tablet ingredients, that is, include both an appropriate spectral range and magnification.…”

Chemical Imaging and Chemometrics: Useful Tools for Process Analytical Technology

“…Our example shows the IR images. However, NIR imaging has proved highly successful in the literature [25] .…”