Discrimination of Pharmaceutical Tablets Based on the Analysis of Solid-State Structures of Ingredients Using...

A frequency-domain terahertz (THz) spectrometer that uses a tunable source, called an injection-seeded THz parametric generator, was applied to the analysis of solid-state structures of ingredients in pharmaceutical tablets, and its performance on discriminating pharmaceutical products was evaluated. The spectrometer has a dynamic range of 70 dB at 2 THz and is suitable for analyzing materials such as pharmaceutical ingredients that often have characteristic absorption peaks between 0.5 and 2.5 THz. Nine ofloxacin (racemate) and four levofloxacin (levorotatory enantiomer) tablet products commercially available in Japan were used as samples. They contain 8-12 additives in addition to the API. The sample tablets were filed down to a thickness of 1.2 mm (ofloxacin tablets) and 1.6 mm (levofloxacin tablets) to obtain transmission spectra over the wide spectral range of 0.8-2.1 THz. The absorption spectra obtained from the spectrometer were preprocessed by the second derivative; then, principal component analysis (PCA) was conducted on the results. Next, quadratic discriminant analysis (DA) was conducted on the scores of the three PCA components. The accuracy of the DA for all 13 products was 96.1%. In addition to the difference in crystal forms of the active ingredient, the small differences in the formulation were clearly discriminated using the THz absorption spectra. The spectrometer combined with data analysis shows potential for applications such as identifying pharmaceutical tablets, monitoring the stability of production processes, evaluating the stability of formulations during storage, and detecting counterfeit drugs on the market.