Terahertz Time of Flight Spectroscopy as a Coating Thickness Reference Method for Partial Least Squares Near Infrared Spectroscopy Models.

Near infrared spectroscopy (NIRS) is often used during the tablet coating process to assess coating thickness. As the coating process proceeds, the increase and decrease in NIRS signal from both the coating formulation and tablet core has been related to coating thickness. Partial least-squares models are often generated relating NIRS spectra to reference coating thickness measurements for in-line and/or at-line monitoring of the coating process. This study investigated the effect of the reference coating thickness measurements on the accuracy of the model. The two primary reference techniques used were weight gain-based coating thickness and terahertz-based coating thickness. Most NIRS coating thickness models currently use weight gain-based reference values; however, terahertz-time-of-flight spectroscopy (THz-TOF) offers a more direct reference coating thickness measurement. Results showed that the accuracy of the NIRS coating thickness model significantly improved when terahertz-based coating thickness measurements were used as reference when compared to weight gain-based coating thickness measurements. Therefore, the application of THz-TOF as a reference method is further demonstrated.