Time-Resolved NIR/Vis Spectroscopy for Analysis of Solids: Pharmaceutical Tablets

Abstract

Time-resolved spectroscopy in the visible and near-infrared (NIR) regions was used in a feasibility study for analysis of solid pharmaceuticals. The objective of the experiments was to study the interaction of light with pharmaceutical solids and to investigate the usefulness of the method as an analytical tool for spectroscopic analysis. In these experiments, a pulsed Ti:sapphire laser and white light generation in water was utilized to form a pulsed light source in the visible/NIR region. The light was focused onto the surface of tablets, and the transmitted light was detected by a time-resolving streak camera. Two types of measurements were performed. First, a spectrometer was put in front of the streak camera for spectral resolution. Secondly, the signal originating from different locations of the sample was collected. Time-resolved and wavelength/spatially resolved data were generated and compared for a number of different samples. The most striking result from the experiments is that the typical optical path length through a 3.5-mm-thick tablet is about 20–25 cm. This indicates very strong multiple scattering in these samples. Monte Carlo simulations and comparison with experimental data support very high scattering coefficients on the order of 500 cm−1. Furthermore, the data evaluation shows that photons with a particular propagation time through the sample contain a higher chemical contrast than other propagation times or than steady-state information. In conclusion, time-resolved NIR spectroscopy yields more information about solid pharmaceutical samples than conventional steady-state spectroscopy.