Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, CB3 0AS Cambridge, UK.
School of Pharmacy, Promis Centre, University of Eastern Finland, P.O. Box 1617, 70211 Kuopio, Finland.
Int J Pharm. 2018 Feb 15;537(1-2):102-110. doi: 10.1016/j.ijpharm.2017.12.029. Epub 2017 Dec 13.
Pharmaceutical tablets are typically manufactured by the uni-axial compaction of powder that is confined radially by a rigid die. The directional nature of the compaction process yields not only anisotropic mechanical properties (e.g. tensile strength) but also directional properties of the pore structure in the porous compact. This study derives a new quantitative parameter, S, to describe the anisotropy in pore structure of pharmaceutical tablets based on terahertz time-domain spectroscopy measurements. The S parameter analysis was applied to three different data sets including tablets with only one excipient (functionalised calcium carbonate), samples with one excipient (microcrystalline cellulose) and one drug (indomethacin), and a complex formulation (granulated product comprising several excipients and one drug). The overall porosity, tablet thickness, initial particle size distribution as well as the granule density were all found to affect the significant structural anisotropies that were observed in all investigated tablets. The S parameter provides new insights into the microstructure of a tablet and its potential was particularly demonstrated for the analysis of formulations comprising several components. The results clearly indicate that material attributes, such as particle size and granule density, cause a change of the pore structure, which, therefore, directly impacts the liquid imbibition that is part of the disintegration process. We show, for the first time, how the granule density impacts the pore structure, which will also affect the performance of the tablet. It is thus of great importance to gain a better understanding of the relationship of the physical properties of material attributes (e.g. intragranular porosity, particle shape), the compaction process and the microstructure of the finished product.
药用片剂通常通过粉末的单轴压缩来制造，粉末被刚性模具径向限制。压缩过程的方向性不仅产生各向异性的机械性能（例如拉伸强度），而且还产生多孔压块中孔结构的方向性。本研究基于太赫兹时域光谱测量，推导出了一个新的定量参数 S，用于描述药用片剂中孔结构的各向异性。S 参数分析应用于三个不同的数据集，包括仅有一种赋形剂（功能化碳酸钙）的片剂、含有一种赋形剂（微晶纤维素）和一种药物（吲哚美辛）的样品，以及一种复杂配方（由几种赋形剂和一种药物组成的颗粒产品）。发现总体孔隙率、片剂厚度、初始颗粒尺寸分布以及颗粒密度均会影响在所有研究片剂中观察到的显著结构各向异性。S 参数提供了对片剂微观结构的新见解，特别是在分析包含多种成分的配方方面具有很大的潜力。结果清楚地表明，材料特性（例如粒径和颗粒密度）会导致孔结构发生变化，从而直接影响作为崩解过程一部分的液体吸收。我们首次展示了颗粒密度如何影响孔结构，这也会影响片剂的性能。因此，深入了解材料属性（例如颗粒内孔隙率、颗粒形状）的物理性质、压缩过程和成品的微观结构之间的关系非常重要。
