Department of Chemical Engineering and Biotechnology, University of Cambridge, Pembroke Street, Cambridge CB2 3RA, U.K.
Mol Pharm. 2012 Dec 3;9(12):3551-9. doi: 10.1021/mp300383y. Epub 2012 Nov 12.
Terahertz pulsed imaging (TPI) is a recently developed nondestructive and noncontact method to measure the coating thickness of coated pharmaceutical tablets. The method requires no calibration in order to resolve the coating structure of tablets. The relative coating thickness over a tablet surface or between different tablets of the same batch can be determined with high precision. However, in order to determine the absolute coating thickness accurately the refractive index, n, of the coating layer needs to be known. For all published studies to date the value of n was based on estimates or bulk measurements, which were based on the assumption that n is constant for a given coating formulation. We have developed a measurement technique using X-ray microtomography to independently quantify the coating thickness. These data were then used to validate the terahertz imaging results, and we found that the intertablet variation of n for coating layers of 25-270 μm thickness is less than 4% and that there is less than 3% intratablet variation in n. Based on our results we estimate that, depending on the pigment content, the absolute value of n in a typical pharmaceutical coating formulation will be in the range of 1.45 < n < 2.01. We conclude that TPI is a robust technique and that, due to its very simple measurement principle, it is an ideal measurement technique to quantify the coating thickness in process control and quality monitoring applications.
太赫兹脉冲成像（TPI）是一种最近开发的无损、非接触式方法，用于测量涂层药物片剂的涂层厚度。该方法不需要校准即可解析片剂的涂层结构。可以高精度地确定片剂表面或同一批次中不同片剂之间的相对涂层厚度。然而，为了准确确定绝对涂层厚度，需要知道涂层层的折射率 n。迄今为止，所有已发表的研究都基于估计值或基于假设 n 对于给定的涂层配方是恒定的的批量测量来确定 n 的值。我们已经开发了一种使用 X 射线微断层扫描的测量技术，可独立定量涂层厚度。然后将这些数据用于验证太赫兹成像结果，我们发现，对于 25-270μm 厚度的涂层，n 在片剂之间的变化小于 4%，而在片剂内部，n 的变化小于 3%。根据我们的结果，我们估计，取决于颜料含量，典型药物涂层配方中 n 的绝对值将在 1.45<n<2.01 的范围内。我们得出结论，TPI 是一种稳健的技术，由于其非常简单的测量原理，它是一种理想的测量技术，可在过程控制和质量监测应用中定量涂层厚度。
