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.
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