Quantitation of active pharmaceutical ingredient through the packaging using Raman handheld spectrophotometers: A comparison study.

Handheld Raman spectroscopy is actually booming. Recent devices improvements aim at addressing the usual Raman spectroscopy issues: fluorescence with shifted-excitation Raman difference spectroscopy (SERDS), poor sensitivity with surface enhanced Raman scattering (SERS) and information only about the sample surface with spatially offset Raman spectroscopy (SORS). While qualitative performances of handheld devices are generally well established, the quantitative analysis of pharmaceutical samples remains challenging. The aim of this study was to compare the quantitative performances of three commercially available handheld Raman spectroscopy devices. Two of them (TruScan and IDRaman mini) are equipped with a 785 nm laser wavelength and operate in a conventional backscattering mode. The IDRaman has the Orbital Raster Scanning (ORS) option to increase the analyzed surface. The third device (Resolve) operates with an 830 nm laser wavelength both in backscattering and in SORS modes. The comparative study was carried out on ibuprofen-mannitol-microcrystalline cellulose ternary mixtures. The concentration of ibuprofen ranged from 24 to 52% (w/w) while the proportions of the two excipients were varied to avoid cross-correlation as much as possible. Analyses were performed either directly through a glass vial or with the glass vial in an opaque polypropylene flask, using a validated FT-NIR spectroscopy method as a reference method. Chemometric analyses were carried out with the Partial Least Squares Regression (PLS-R) algorithm. The quantitative models were validated using the total error approach and the ICH Q2 (R1) guidelines with ± 15% as acceptance limits.