Evaluation of laser direct infrared imaging for rapid analysis of pharmaceutical tablets.

Vibrational spectroscopic chemical imaging is an important tool in the pharmaceutical industry for characterising the spatial distribution of components within final drug products. The applicability of these techniques is currently limited by the long data acquisition times required to obtain high-definition chemical images of a sample surface. Advancements in quantum cascade laser (QCL) technology have provided an exciting new opportunity for infrared (IR) imaging. Instead of collecting a full IR spectrum at each point, it is possible to focus on distinct spectral bands to reduce imaging data collection time. This study explores a laser direct infrared (LDIR) chemical imaging approach that couples QCL technology with rapid scanning optics to provide high-definition chemical images at an order of magnitude faster than traditional imaging techniques. The capabilities of LDIR chemical imaging were evaluated for pharmaceutical formulations and compared with other established spectroscopic chemical imaging techniques including Raman, near-infrared (NIR) and scanning electron microscopy-energy dispersive X-ray (SEM-EDX) spectroscopy with regards to data acquisition time and image quality. The study showed that LDIR imaging provided high-definition component distribution maps comparable to Raman and SEM-EDX at orders of magnitude faster in terms of time. The ability to obtain high-definition chemical images of the whole tablet surface in relatively fast time frames indicates LDIR imaging could be a promising tool in the pharmaceutical industry to rapidly characterise the size and distribution of components within tablets and could help enhance drug product manufacturing understanding.

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

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 1s acquisition times, respectively.