A comparative study of applying backscattering and transmission Raman spectroscopy to quantify solid-state form conversion in pharmaceutical tablets

Abstract

Selecting appropriate Raman measurement and data processing method are of importance to enable effective quantification of solid form conversions upon processing or storage. Therefore, a comparative evaluation is presented herein on using backscattering and transmission Raman spectroscopy to quantify salt disproportionation in tablet matrices. The second part focuses on different spectra processing approaches and calibration models for quantifications. Finally, samples under different mechanical stresses were comprehensively analyzed using different Raman measurements. Much as transmission Raman spectrometry may provide accuracy on bulk measurements by having large sampling volume, it has the drawback of signal attenuation and may overlook process-induced phase transitions occurring on local regions of tablet surface. To overcome this limitation, backscattering Raman with deliberate subsampling can be used as an orthogonal method to probe the existence of low-level form conversion distributed over a tablet’s surface. In the present case, different levels of the form conversions were found at the edge and the center of tablets due to the uneven shear stress distribution invoked during tablet compression. In such a scenario, it would be beneficial to apply deliberate-focused backscattering and transmission Raman spectrometry together as complementary techniques to capture chemical information both locally and within the bulk of the tablet.