Method development and validation of a near-infrared spectroscopic method for in-line API quantification during fluidized bed granulation

[Display omitted] •The first time using EIOT to monitor API content during fluidized bed granulation.•The spatial distribution of API in granules was visualized by Raman imaging.•The performance of EIOT and PLS on API quantification was compared.•The robustness of EIOT was evaluated through the design of experiment. Near-infrared spectroscopy (NIRS) is an excellent process analytical technology (PAT) tool for active pharmaceutical ingredient (API) quantification during fluidized granulation. Therefore, a portable near-infrared spectrometer combined with a new innovative method of extended iterative optimization technique (EIOT) was used to in-line monitor the API content uniformity during fluidized bed granulation. The principal component analysis (PCA) and partial least squares regression (PLSR) were also used to characterize and predict API concentration with changes from 75% to 125% of the label claim to prove the superiority of EIOT. The API content prediction accuracy of the EIOT method was verified through offline High Performance Liquid Chromatography (HPLC) measurement. Also, the spatial distribution of API in granules was visualized by Raman imaging technology. The results showed that the established NIRS method was suitable for the prediction of API content in fluidized bed granulation, which provides a new idea for the determination of API content during granulation.