Penetration depth and effective sample size characterization of UV/Vis radiation into pharmaceutical tablets.

The pharmaceutical industry is moving from off-line to real-time release testing (RTRT) to enhance quality while reducing costs. UV/Vis spectroscopy has emerged as a promising tool for RTRT given its simplicity, sensitivity and cost-effectiveness. Nevertheless, the effective sample size must be characterized in relation to the penetration depth to justify its representativeness and suitability for RTRT. In this study, bilayer tablets were produced using a hydraulic tablet press. The lower layer contained titanium dioxide and microcrystalline cellulose (MCC), while the upper layer consisted of MCC, lactose or a combination with theophylline. The thickness of the upper layer was stepwise increased. Spectra from 224 to 820 nm were recorded with an orthogonally aligned UV/Vis probe. Thereby, the experimental penetration depth reached up to 0.4 mm, while the Kubelka-Munk model yielded a theoretical maximum penetration depth of 1.38 mm. Based on these values, the effective sample sizes were determined. Considering a parabolic penetration profile, the maximum volume was 2.01 mm³. The results indicated a wavelength and particle size dependency. Micro-CT analysis confirmed the even distribution of the API in the tablets proving the sufficiency of the UV/Vis sample size. Consequently, UV/Vis spectroscopy is a reliable alternative for RTRT in tableting.