In-line monitoring of Ibuprofen during and after tablet compression using near-infrared spectroscopy

Abstract

Near infrared spectroscopy (NIRS) used as process analytical technology tool to monitor Active Pharmaceutical Ingredient concentrations during tablet manufacturing has been reported to enhance overall product quality assurance. NIRS applications in different manufacturing stages are facilitated by their ability to handle different sample presentations - be it solids, liquids, gels or powders. The present study evaluates NIRS suitability for monitoring Ibuprofen concentrations (coated pellets form) inside the feed frame of a tableting press as well as in output tablets. Process monitoring was undertaken with quantitative chemometric analysis. NIRS-based predictions of concentrations both inside the feed frame and in tablets were compared to ultraviolet (UV) spectroscopy assays of temporally stratified tablet samples. Process dynamics were also compared in terms of concurrent concentrations change kinetics in the feed frame and in output tablets. NIRS showed good sensitivity to Ibuprofen concentrations despite the use of coated pellets. Ibuprofen contents as low as 1.7% w/w were detected effectively. NIRS-based quantitative predictions in the feed frame and in tablets closely matched the UV assay values of sampled tablets. As anticipated from the 2-wheel feed frame geometry, upon the addition of each consecutive blend, results show that the predicted concentration inside the feed frame were delayed compared with that of the tablets exiting the tablet press. For these tests, the delay was estimated to be 1.25 min. This finding highlights the importance of NIRS probe position inside the feed frame as a function of its geometry. Successive feed frame and tablet monitoring by NIRS could prove beneficial for real time release testing of tablet formulations.

Keywords: Chemometric analysis; Feed frame; NIRS; PAT; Real time release testing; Tablet.