Terahertz (THz) spectroscopy is expected as a new technique for nondestructive inspection of pharmaceutical tablets, because THz waves pass through a wide variety of pharmaceutical materials. We have been developing a frequency domain THz spectrometer with an injection-seeded THz parametric generation (is-TPG) technique. In this study, the frequency range of the spectrometer was successfully expanded to 0.9-4.2 THz by generating widely tunable THz waves by shifting a nonlinear crystal to balance gain and absorption of the THz waves in the crystal, and detecting the THz waves with an angle-compensation method that utilized the dispersion of the crystal. Absorption spectra of the crystal polymorphs of carbamazepine forms I and III were obtained with the THz spectrometer, and these polymorphs were identified by specific absorption peaks related to their solid state.
The pharmaceutical industry requires a simple nondestructive quantitative inspection technique that does not change the characteristic properties of the target of inspection. Terahertz (THz) spectroscopy has potential as a nondestructive inspection technique because of the high transmittance of inspected materials and the absorption peaks related to some active pharmaceutical ingredients (APIs) in THz frequency regions. We have developed a compact terahertz spectroscopy system that uses an injection-seeded terahertz parametric generator (is-TPG) as a THz light source for the inspection and quantitative analysis of pharmaceutical tablets. Using this system, acetylsalicylic acid, acetaminophen, tranexamic acid, loxoprofen sodium, and caffeine included in over-the-counter (OTC) medicine tablets were identified as APIs by their specific absorption peaks. We also conducted a quantitative analysis of acetaminophen in one of the medicines by performing multivariate analyses. The root-mean-squared error of cross-validation (RMSECV) was 0.297 wt%. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.990 wt% and 3.00 wt%, respectively. These results indicate that this is-TPG system could be applied as an inspection and quantitative analysis technique for OTC medicine tablets.
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