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

Abstract: The pharmaceutical industry is moving from off-line quality testing to real-time release testing (RTRT) to improve drug quality while reducing costs. The implementation of RTRT requires advanced in-line process analytics, where UV/Vis spectroscopy has proven its suitability. However, quantification of the sample size requires detailed knowledge of the penetration depth. 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 mm$<sup>3$. 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.