Potential of Raman Spectroscopy for Evaluating Crushing Strength of Tablets

This study evaluates the sensitivity of Raman spectroscopy to changes in physical attributes of the compacted pharmaceutical formulations prepared with lactose monohydrate (49 wt.%), microcrystalline cellulose (49 wt.%), silicone dioxide (1 wt.%), and magnesium stearate (1 wt.%). The tablets made with raw powder were subjected to two iterative dry granulation cycles, i.e., tablet crushing, sieving, and re-tableting. Different compaction forces were applied during tableting. Small- and wide-angle X-ray scattering was used to study physical changes of the granulates and their respective compacts. Small-angle X-ray scattering spectra indicated larger particle-particle interfaces with increasing compaction force. Wide-angle X-ray scattering spectra revealed no changes in the crystalline structure (morphology) of materials in the granulates and tablets before and after the dry granulation. Raman spectra showed attenuated backscattering signal with increasing compaction force or crushing strength. Principal component analysis and partial least squares regression were used for spectral pattern recognition and for quantitative crushing strength prediction. Attenuated Raman backscattering signal with increasing compaction force was due to (1) smoothing of the tablet surface, which leads to smaller surface area, hence reducing sample-light interactions and (2) larger particle-particle interfaces which lead to enhanced light scattering in the direction of the incident light, causing light absorption by the tablet.