Schomberg Ann Kathrin, Diener Alexander, Wünsch Isabell, Finke Jan Henrik, Kwade Arno
Technische Universität Braunschweig, Institute for Particle Technology, Volkmaroder Straße 5, 38104 Braunschweig, Germany.
Technische Universität Braunschweig, Center of Pharmaceutical Engineering (PVZ), Franz-Liszt-Straße 35A, 38106 Braunschweig, Germany.
Int J Pharm X. 2021 Jul 10;3:100090. doi: 10.1016/j.ijpx.2021.100090. eCollection 2021 Dec.
Within this study, tablets microstructure was investigated by X-ray microtomgraphy. The aim was to gain information about their microstructure, and thus, derive deeper interpretation of tablet properties (mechanical strength, component distribution) and qualified property functions. Challenges in image processing are discussed for the correct identification of solids and voids. Furthermore, XMT measurements are critically compared with complementary physical methods for characterizing active pharmaceutical ingredient (API) content and porosity and its distribution (mercury porosimetry, calculated tablet porosity, Focused Ion Beam-Scanning Electron Microscopy (FIB-SEM)). The derived porosity by XMT is generally lower than the calculated porosity based on geometrical data due to the resolution of the XMT in relation to the pore sizes in tablets. With rising compactions stress and API concentration, deviations between the actual and the calculated API decrease. XMT showed that API clusters are present for all tablets containing >1 wt% of ibuprofen. The 3D orientation of the components is assessable by deriving cord lengths along all dimensions of the tablets. An increasing compaction stress leads to rising cord lengths, showing higher connectivity of the respective material. Its lesser extent in the z-direction illustrates the anisotropy of the compaction process. Additionally, cracks in the fabric are identified in tablets without visible macroscopic damage. Finally, the application of XMT provides valuable structural insights if its limitations are taken into account and its strengths are fostered by advanced pre- and post-processing.
在本研究中,通过X射线显微断层扫描技术对片剂的微观结构进行了研究。目的是获取有关其微观结构的信息,从而更深入地解释片剂的性能(机械强度、成分分布)及其合格的性能功能。讨论了图像处理中在正确识别固体和空隙方面的挑战。此外,还对XMT测量结果与用于表征活性药物成分(API)含量、孔隙率及其分布的补充物理方法(压汞法、计算片剂孔隙率、聚焦离子束扫描电子显微镜(FIB-SEM))进行了严格比较。由于XMT相对于片剂孔隙尺寸的分辨率,通过XMT得出的孔隙率通常低于基于几何数据计算得出的孔隙率。随着压制应力和API浓度的增加,实际API与计算API之间的偏差减小。XMT显示,对于所有含有>1 wt%布洛芬的片剂,均存在API聚集体。通过沿片剂所有维度得出弦长,可以评估各成分的三维取向。压制应力的增加会导致弦长增加,表明相应材料的连通性更高。其在z方向上程度较小说明了压制过程的各向异性。此外,在没有明显宏观损伤的片剂中发现了结构中的裂纹。最后,如果考虑到XMT的局限性并通过先进的预处理和后处理发挥其优势,XMT的应用将提供有价值的结构见解。