Chemical and Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, NJ 08854, USA.
Chemical and Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, NJ 08854, USA.
Int J Pharm. 2022 Jan 5;611:121331. doi: 10.1016/j.ijpharm.2021.121331. Epub 2021 Dec 2.
A better understanding of a pharmaceutical tablet's microstructure has the potential to unlock the black box between material attributes, process parameters and the critical quality attributes. Microstructure determination requires measuring the spatial-, particle size-distributions (absolute and relative) of the ingredients, and the void space, which is the overt goal of chemical Imaging (CI). Reliable quantitative results can be obtained by imaging multiple layers per tablet, with each layer having a minimal surface roughness. This study utilized scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) and Raman chemical imaging (RCI) to provide a comparative discussion of results obtained when determining the microstructure of commercial zinc sulfate tablets, using three methods of tablet surface preparation: scoring & hand-fracturing, microtoming, and grating. A description of the working principles of the measurement and surface preparation methods is followed by a comparison of microstructure (particle size distribution and homogeneity of distribution) using chemical images. A comparison of the general advantages and disadvantages of SEM/EDX and RCI and the common errors in analyzing microstructure are also discussed. The results indicate that in addition to selecting the correct tablet surface preparation method, chemical imaging method, and the subsequent microstructural analyses method, correct problem formulation is also critical.
更好地了解药物片剂的微观结构有可能揭示材料属性、工艺参数和关键质量属性之间的“黑箱”。微观结构的确定需要测量成分的空间、粒径分布（绝对和相对）和空隙空间，这是化学成像（CI）的明显目标。通过对每个片剂的多层进行成像，可以获得可靠的定量结果，每层的表面粗糙度最小。本研究利用扫描电子显微镜/能量色散 X 射线光谱（SEM/EDX）和拉曼化学成像（RCI），对使用三种片剂表面制备方法（划痕和手动断裂、微切割和格栅）确定商业硫酸锌片剂微观结构时获得的结果进行了比较讨论。首先描述了测量和表面制备方法的工作原理，然后使用化学图像比较了微观结构（粒径分布和分布均匀性）。还讨论了 SEM/EDX 和 RCI 的一般优缺点以及分析微观结构时的常见错误。结果表明，除了选择正确的片剂表面制备方法、化学成像方法和随后的微观结构分析方法外，正确的问题表述也至关重要。
