Assessment of crystalline carbamazepine in bilayer tablets by transmission low-frequency Raman spectroscopy

Assessment of crystalline phases in multilayer pharmaceutical tablets is analytically challenging because differences in layer composition and thickness strongly influence light propagation, scattering, and attenuation of spectroscopic signals. In this study, transmission low-frequency Raman spectroscopy was employed to examine how measurement geometry affects the detectability of lattice vibrational features arising from crystalline carbamazepine embedded within bilayer tablets containing crystalline and amorphous regions. Bilayer tablets were prepared by systematically varying the crystalline carbamazepine fraction in the lower layer (10-60%, w/w) and the thickness of the upper excipient or amorphous layer. Transmission-mode measurements provided stable low-frequency Raman signals independent of measurement orientation, whereas conventional backscattering spectra were strongly affected by surface selection and overlayer thickness. Characteristic lattice vibrational bands of carbamazepine Form III, particularly the band at 37 cm^-1, remained clearly detectable even at low crystalline levels beneath an amorphous-rich overlayer, reflecting the depth-averaged nature of transmission Raman sampling. Multivariate analysis was applied as a supporting tool to visualize systematic spectral variations associated with crystalline content in the bilayer structure. These results clarify how transmission-mode low-frequency Raman spectroscopy preserves lattice vibrational information in optically heterogeneous layered systems and demonstrate its suitability for spectroscopic characterization of structurally complex pharmaceutical solids.