Campbell University College of Pharmacy & Health Sciences, Buies Creek, NC 27506, United States.
Division of Pharmaceutics Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, The Long Island University, Brooklyn, NY 11201-5497, United States.
Eur J Pharm Biopharm. 2018 Nov;132:83-92. doi: 10.1016/j.ejpb.2018.09.006. Epub 2018 Sep 10.
Anisotropic features with other crystallographic properties like d-spacing, and attachment energy (E) can predict material performance during the secondary pharmaceutical processing. A newly developed state-of-the-art compression cell lodged in a powder X-ray diffractometer was used to measure anisotropic Young's moduli (YM) of flufenamic acid (FFA) polymorphs in this study. Methodology is based on the generation of a single crystal deformation in this cell, which reflects as a change in the d-spacing in the PXRD pattern. Anisotropic YM was calculated from such information gathered along different FFA planes. Measured FFA crystallographic molecular features were concatenated to understand macroscopic compaction (Heckel and Shapirao's parameters) and tableting performance. Block shaped crystals of FFA form I, and III after initial characterization with SEM, DSC, PXRD, and FTIR were compressed normal to X, Y, and Z-planes, identified from calculated PXRD pattern using the reported single crystal structure. YM of X and Y planes of form I was significantly higher than corresponding planes of form III. Z plane of form III showed significantly higher YM than that for form I. Low YM of form III can be attributed to its large d-spacing regardless of their high E than form I, as well as orientation of supramolecular acid dimer (OH⋯O) homosynthon chains in the FFA planes. FFA form I stiffness was further confirmed with lower densification and higher yield pressure of deformation than form III. Clearly, form III exhibited better compressibility, compactibility, and tableting performance than form I due to favorable molecular and macroscopic features. Thus, developed anisotropic measurement approach can be used to distinguish material performance in the early development stage of the pharmaceutical processes.
各向异性特征与其他晶体学性质（如 d 间距和附着能（E））可预测药物加工过程中的二次材料性能。在这项研究中，使用一种新开发的最先进的压缩室安装在粉末 X 射线衍射仪中，以测量 flufenamic 酸（FFA）多晶型物的各向异性杨氏模量（YM）。该方法基于在该细胞中产生单晶变形，这反映为 PXRD 图案中 d 间距的变化。从沿不同 FFA 平面收集的这些信息计算各向异性 YM。测量的 FFA 晶体学分子特征被串联起来，以了解宏观压缩（Heckel 和 Shapirao 参数）和压片性能。在 SEM、DSC、PXRD 和 FTIR 对 FFA 形式 I 和 III 的初始特征进行初始表征后，形成块状晶体，然后在 X、Y 和 Z 平面上垂直压缩，这些平面是根据报告的单晶结构从计算的 PXRD 图案中识别出来的。形式 I 的 X 和 Y 平面的 YM 明显高于形式 III 的相应平面。形式 III 的 Z 平面的 YM 明显高于形式 I 的 YM。尽管 III 形式的 E 值高于 I 形式，但其 YM 较低，这可以归因于其较大的 d 间距，以及 FFA 平面中超分子酸二聚体（OH⋯O）同系物链的取向。与形式 III 相比，FFA 形式 I 的硬度更低，这是由于其较低的致密化和较高的屈服压力变形。显然，由于有利的分子和宏观特征，形式 III 表现出比形式 I 更好的可压缩性、可压缩性和压片性能。因此，这种开发的各向异性测量方法可用于在药物加工过程的早期开发阶段区分材料性能。
