Non-invasive quantitative assessment of the content of pharmaceutical capsules using transmission Raman spectroscopy

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This study demonstrates how transmission Raman spectroscopy can be used in the quantitative, non-invasive probing of the bulk content of production line relevant pharmaceutical products contained within capsules with a strong interfering Raman signal (principally TiO 2). This approach is particularly beneficial in situations where the conventional Raman backscattering method is hampered or fails due to excessive Raman or fluorescence signals emanating from surface layers (capsule or coating) that pollute the much weaker subsurface Raman signals. In these feasibility experiments the interfering surface Raman signal was effectively suppressed, relative to the Raman signal of the internal content, by a factor of 33, in the transmission geometry in comparison with the conventional backscattering Raman approach. In conjunction with the superior bulk probing ability of the transmission Raman geometry, which effectively removes the sub-sampling problem inherent to conventional Raman spectroscopy, and multivariate analysis (principal component analysis (PCA), partial least squares (PLS) and classical least squares (CLS) regression), this provides an analytical tool well suited for rapid control monitoring applications in the pharmaceutical industry. The measured relative root mean square error of prediction (RMSEP) of the concentration of the active pharmaceutical ingredient (API) was 1.2 and 1.8% with 5 and 1 s acquisition times, respectively.