A Quantitative Chemometric Study of Pharmaceutical Tablet Formulations Using Multi-Spectroscopic Fibre Optic Probes.

Two fibre optic probes were custom designed to perform Raman and near-infrared spectroscopic measurements. Our long-term objective is to develop a non-destructive tool able to collect data in hard-to-access locations for real-time analysis or diagnostic purposes. This study evaluated the quantitative performances of Probe A and Probe B using model pharmaceutical tablets. Measurements were performed using pharmaceutical tablets containing hydroxyl propylcellulose, titanium dioxide (anatase), lactose monohydrate, and indomethacin (γ form). Material content and thickness of bilayer samples (samples consisting of a top layer and a bottom layer of differing materials) were also assessed using Probe A to evaluate its capabilities to collect sub-surface information. Principal component analysis and partial least squares regression models were using individual and fused data to evaluate the performances of the different probe configurations. Hydroxymethyl cellulose (RP2=0.98, RMSEP = 2.27% /) and lactose monohydrate (RP2=0.97, RMSEP = 2.96% /) content were most effectively estimated by near-infrared spectroscopy data collected using Probe A. Titanium dioxide (RP2=0.99, RMSEP = 0.21% /) content was most effectively estimated using a combination of 785 nm Raman spectroscopy and near-infrared spectroscopy using Probe B. Indomethacin (RP2=0.97, RMSEP = 1.01% /) was best estimated using a low-level fused dataset collected using 0 mm, 2.5 mm, and 5.0 mm lateral offsets of 785 nm spatially offset Raman spectroscopy using Probe A. The different probe configurations were able to reliably collect data and demonstrated robust quantitative performances. These results highlight the advantage of using multiple techniques for analysing different structures.