Institute of Photonics, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland.
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom.
Eur J Pharm Biopharm. 2016 Aug;105:122-33. doi: 10.1016/j.ejpb.2016.06.007. Epub 2016 Jun 8.
In this study, terahertz time-domain spectroscopic (THz-TDS) technique has been used to ascertain the change in the optical properties, as a function of changing porosity and mass fraction of active pharmaceutical ingredient (API), of training sets of pharmaceutical tablets. Four training sets of pharmaceutical tablets were compressed with microcrystalline cellulose (MCC) excipient and indomethacin API by varying either the porosity, height, and API mass fraction or all three tablet parameters. It was observed, as far as we know, for the first time, that the THz time-domain and frequency-domain effective refractive index, as well as, the frequency-domain effective absorption coefficient both show linear correlations with the porosity and API mass fraction for training sets of real pharmaceutical tablets. We suggest that, the observed linear correlations can be useful in basic research and quality inspection of pharmaceutical tablets. Additionally, we propose a novel optical strain parameter, based on THz measurement, which yields information on the conventional strain parameter of a tablet as well as on the change of fill fraction of solid material during compression of porous pharmaceutical tablets. We suggest that the THz measurement and proposed method of data analysis, in addition to providing an efficient tool for basic research of porous media, can serve as one of the novel quality by design (QbD) implementation techniques to predict critical quality attributes (CQA) such as porosity, API mass fraction and strain of flat-faced pharmaceutical tablets before production.
在这项研究中，太赫兹时域光谱（THz-TDS）技术已被用于确定随多孔性和活性药物成分（API）质量分数变化的光学性质变化，这些变化是训练集的片剂。通过改变孔隙率、高度和 API 质量分数或所有三个片剂参数，用微晶纤维素（MCC）赋形剂和吲哚美辛 API 压缩了四个训练集的片剂。据我们所知，这是第一次观察到，THz 时域和频域有效折射率以及频域有效吸收系数都与真实药用片剂的训练集的孔隙率和 API 质量分数呈线性相关。我们建议，观察到的线性相关性可用于药用片剂的基础研究和质量检查。此外，我们基于太赫兹测量提出了一种新的光学应变参数，该参数可提供片剂常规应变参数以及在多孔药用片剂压缩过程中固体材料填充分数变化的信息。我们建议，太赫兹测量和提出的数据分析方法除了为多孔介质的基础研究提供一种有效的工具外，还可以作为设计质量（QbD）实施技术之一，用于预测关键质量属性（CQA），如孔隙率、API 质量分数和平坦片剂的应变在生产之前。
