Lyon Robbe C, Lester David S, Lewis E Neil, Lee Eunah, Yu Lawrence X, Jefferson Everett H, Hussain Ajaz S
Division of Product Quality Research, Food and Drug Administration, Kensington, MD 20895, USA.
AAPS PharmSciTech. 2002;3(3):E17. doi: 10.1208/pt030317.
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.
本研究的目的是评估近红外（NIR）光谱成像作为一种工具，以解决药品质量保证问题——最终剂型产品中的混合均匀性。基于阵列探测器技术的系统被用于快速收集速尿片的高对比度近红外图像。通过改变混合程度，制备了5个等级的实验片剂，它们含有相同量的速尿和微晶纤维素，从混合良好到未混合不等。为作比较，这些片剂也采用传统近红外光谱法进行分析，两种方法都用于评估药品的均匀性。近红外光谱成像能够在定性和定量方面清晰地区分每个混合等级。各成分的空间分布基于像素强度的变化或对比度，这是由于近红外光谱对每个像素的贡献所致。每个像素的化学性质可通过与每个像素相关的局部光谱来识别。单变量图像和偏最小二乘法（PLS）图像均进行了评估。在次优混合的片剂中，通过图像目视检查可明显看出不均匀区域。通过计算PLS得分图像中像素强度分布的标准差来确定混合的定量指标。从混合良好的片剂到未混合的片剂，标准差百分比从11%逐渐增加到240%。近红外光谱成像系统为获取药品的空间和光谱信息提供了一种快速方法。该技术在产品质量保证方面有多种应用潜力，并可能影响制造过程的控制。
