Establishing quantitative in-line analysis of multiple solid-state transformations during dehydration

The aim of the study was to conduct quantitative solid phase analysis of piroxicam (PRX) and carbamazepine (CBZ) during isothermal dehydration in situ, and additionally exploit the constructed quantitative models to analyze the solid-state forms in-line during fluidized bed drying. Vibrational spectroscopy (near-infrared (NIR), Raman) was employed for monitoring the dehydration and the quantitative model was based on partial least squares (PLS) regression. PLS quantification was confirmed experimentally using isothermal thermogravimetric analysis (TGA) and X-ray powder diffractometry (XRPD). To appraise the quality of quantitative models several model parameters were evaluated. The hot-stage spectroscopy quantification results were found to be in reasonable agreement with TGA and XRPD results. Quantification of PRX forms showed complementary results with both spectroscopic techniques. The solid-state forms observed during CBZ dihydrate dehydration were quantified with Raman spectroscopy, but NIR spectroscopy failed to differentiate between the anhydrous solid-state forms of CBZ. In addition to in situ dehydration quantification, Raman spectroscopy in combination with PLS regression enabled in-line analysis of the solid-state transformations of CBZ during dehydration in a fluidized bed dryer.