Fluorescence spectroscopy on smooth and rough solid pharmaceutical surfaces

Fluorescence spectroscopy is an inherently sensitive and fast method that could be a powerful addition to existing process analytical technology (PAT) tools for non-destructive quantification of active pharmaceutical ingredients (API) in low-dose formulations. However, the fundamental physical factors influencing the fluorescence signal response remain poorly understood. In this study, bench-top solid state fluorescence spectroscopy was used to systematically examine the effects of API concentration, surface roughness, and compaction pressure on the fluorescence response of low-dose solid pharmaceutical samples. A solid formulation using tryptophan as a model fluorophore was prepared across a range of blend concentrations (0.10 - 0.50 % w/w), three compaction pressures, and three granule milling screen sizes. Clear and systematic distinctions in fluorescent signal were observed across API concentrations in powder blends, compacts, and granules. Compaction pressure induced systematic changes in fluorescent signal across both smooth and rough sample surfaces. Milling screen size showed no noticeable effect on the signal, whereas the granule particle size influenced the fluorescence response alongside changes in API concentration. Despite this influence of the particle size, a regression model showed promising concentration predictions upon cross-validation. These findings advance the fundamental understanding of fluorescence signal behaviour in solid pharmaceutical systems, supporting further development of fluorescence spectroscopy as a relevant technique for pharmaceutical challenges.