Investigation of the effects of tableting parameters on reliable quantitative terahertz spectroscopy

Particle size ratio, tablet thickness, and compaction pressure are three important tableting parameters that affect the obtained tablet spectrum. In this study, the single-factor test and response surface analysis (RSM) were adopted to examine how these three parameters and their interactions affect the analytical measurements performed over terahertz time-domain spectroscopy (THz-TDS). Tablet samples were composed of a different percent (wt-%) of acetylsalicylic acid within microcrystalline cellulose. Results indicate that change in absorption coefficient was found to be more obvious for a larger particle size ratio. Thinner tablets were sensitive to absorption coefficient effects created as the transmitted THz radiation propagates through the tablet interfaces. Compression pressure has a limited effect on the absorption coefficient. The particle size ratio had the largest effect on the coefficient of correlation of the quantitative regression model, followed by the compaction pressure, and the tablet thickness. In this study, the optimized tableting parameters were determined: tablet thickness of 0.48 mm, particle size ratio of about 1:1, and compaction pressure of 30 MPa. Under this condition, the R² of the quantitative regression model of acetylsalicylic acid content was 0.971 and 0.998 at the range of acetylsalicylic acid mass fraction between 10 and 90 wt-%, 1 and 30 wt-%, respectively. This study provides a method to effectively reduce the scattering effect of spectral detection of tablets by improving the sample’s properties, to provide a reference for enhancing the reliability and accuracy of quantitative measurements.