Implementation-focused evaluation of transmission low-frequency Raman spectroscopy parameters for non-destructive quality control of solid dosage forms

Abstract

Transmission low-frequency Raman spectroscopy (TLRS) offers unique advantages for non-destructive characterization of crystalline phases in pharmaceutical solid dosage forms. While the analytical principle has been previously demonstrated, its practical implementation for routine quality control (QC) has not been systematically assessed. This study evaluates the effects of key formulation and measurement parameters—tablet thickness, compaction pressure, particle size, and laser power—on TLRS performance using intact amorphous carbamazepine tablets containing crystalline Form III. In transmission mode, spectral intensity peaked at an optimal thickness and decreased at higher compaction pressures, while smaller particle sizes provided more reproducible spectra and improved semi-quantitative accuracy. Principal component analysis (PCA) enabled clear discrimination and compositional ranking for low-level crystalline content (≥5%) across a 0–30% loading range. These findings provide practical insights into TLRS implementation and indicate its potential utility for future analytical applications.