Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, UK.
J Pharm Sci. 2011 Apr;100(4):1535-44. doi: 10.1002/jps.22359. Epub 2010 Oct 18.
We present a new in-line measurement technique to determine the coating thickness of individual pharmaceutical tablets during film coating in a pan coating unit using pulsed terahertz technology. Results of these real-time terahertz measurements acquired during a production scale coating run are validated using both off-line high-resolution terahertz pulsed imaging of the whole dosage form as well as weight-gain measurements made on sample tablets removed at discrete time intervals during the process run. The terahertz measurements provide a direct method of determining the coating thickness, and no chemometric calibration models are required for the quantification. The results, and their repeatability, demonstrate that real-time monitoring of pharmaceutical tablet coating is not only possible but also provides substantially more information of the coating quality than the standard quality control method. Rather than providing the average coating thickness of a large number of tablets, the terahertz sensor provides the thickness of up to 100 individual tablet coatings per minute. Using this information, the operator can get additional information about the thickness distribution in the coating pan and adjust the process accordingly. At present, a minimum coating thickness of 40 μm is required to determine the coating thickness. The technique is applicable for coatings up to 1 mm in thickness. Within that range, it provides thickness measurements of sub-micron resolution. Terahertz in-line coating process measurements show considerable potential for applications in real-time release, process analytical technology and quality by design.
我们提出了一种新的在线测量技术，用于在盘式涂层机中使用脉冲太赫兹技术在薄膜涂层过程中确定单个药片的涂层厚度。通过离线高分辨率太赫兹脉冲成像以及在过程运行期间离散时间间隔从样品片中进行的增重测量，对生产规模涂层运行过程中实时太赫兹测量结果进行了验证。太赫兹测量提供了一种直接确定涂层厚度的方法，不需要进行化学计量校准模型进行定量。结果及其重复性表明，不仅可以实时监测药物片剂的涂层，而且与标准质量控制方法相比，还可以提供更多有关涂层质量的信息。太赫兹传感器每分钟提供多达 100 个单个片剂涂层的厚度，而不是提供大量片剂的平均涂层厚度。使用此信息，操作人员可以获得有关涂层锅中厚度分布的其他信息，并相应地调整过程。目前，需要 40μm 的最小涂层厚度来确定涂层厚度。该技术适用于厚度达 1mm 的涂层。在该范围内，它提供了亚微米分辨率的厚度测量。太赫兹在线涂层过程测量在实时释放、过程分析技术和设计质量方面具有很大的应用潜力。
