Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK; EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, University of Strathclyde, Glasgow, UK.
Int J Pharm. 2019 Dec 15;572:118766. doi: 10.1016/j.ijpharm.2019.118766. Epub 2019 Nov 6.
Optical Coherence Tomography (OCT) is a promising technology for monitoring of pharmaceutical coating processes. However, the pharmaceutical development and manufacturing require a periodic validation of the sensor's accuracy. For this purpose, we propose polyethylene terephthalate (PET) films as a model system, to periodically validate the measurements during manufacturing. This study proposes a new approach addressing the method validation requirement in the pharmaceutical industry and presents results for complementary methods. The methods investigated include direct measurement of the layer thickness using a micrometer gauge as reference, X-ray micro computed tomography, transmission and reflectance terahertz pulsed imaging, as well as 1D- and 3D-OCT. To quantify the significance of OCT for pharmaceutical coatings, we compared the OCT results for commercial Thrombo ASS and Pantoloc tablets with direct measurements of coating thickness via light microscopy of microtome cuts. The results of both methods correlate very well, indicating high intra- and inter-tablet variations in the coating thickness for the commercial tablets. The light microscopy average measured coating thickness of Thrombo ASS (Pantoloc) was 71.0 µm (83.7 µm), with an inter-coating variability of 8.7 µm (6.5 µm) and an intra-coating variability of 2.3 µm to 9.4 µm (2.1 µm to 6.7 µm).
光学相干断层扫描（OCT）是一种很有前途的药物涂层工艺监测技术。然而，药物研发和制造需要定期验证传感器的准确性。为此，我们提出使用聚对苯二甲酸乙二醇酯（PET）薄膜作为模型系统，以便在制造过程中定期验证测量结果。本研究提出了一种新方法来满足制药行业的方法验证要求，并展示了补充方法的结果。研究的方法包括使用千分尺作为参考直接测量层厚度、X 射线微计算机断层扫描、透射和反射太赫兹脉冲成像，以及 1D 和 3D-OCT。为了量化 OCT 在药物涂层中的重要性，我们将商业血栓 ASS 和 Pantoloc 片剂的 OCT 结果与通过显微镜切割的光显微镜直接测量涂层厚度的结果进行了比较。两种方法的结果相关性非常好，表明商业片剂的涂层厚度在片剂内和片剂间存在较大差异。光显微镜平均测量的血栓 ASS（Pantoloc）涂层厚度为 71.0 µm（83.7 µm），涂层间变异性为 8.7 µm（6.5 µm），涂层内变异性为 2.3 µm 至 9.4 µm（2.1 µm 至 6.7 µm）。
