Cohesive, multicomponent, dense powder flow characterization by NIR

Non-aerated powder flows are frequently encountered in downstream pharmaceutical processes. Such flows occur at the entrance of powder compression units, and their characteristics are of great interest because any powder agglomeration or segregation can be detrimental to the quality of the final solid oral dosage form. This work was aimed at developing a process analytical technology (PAT) method, based on near-infrared spectroscopy (NIR) for the in-line powder flow characterization of pharmaceutical formulations. An Ibuprofen drug formulation was selected for study. A bench-scale hopper system was assembled to monitor powder flow behaviour. An in-line commercial NIR Axsun spectrometer and probe were chosen to collect in-line spectral data on dense, multicomponent, non-aerated powder flow prior to compression. Spectra were collected on flowing mannitol and pharmaceutical product blends. A specially designed, non-contact sampling interface allowed the collection of representative process powder flow spectra without affecting blend uniformity. A partial least squares chemometric model was developed for laboratory-prepared samples, to quantitatively determine the flowing powder's active pharmaceutical ingredient (API) level. Static sample spectra and flowing pure mannitol spectra proved to have a high degree of reproducibility. The model's standard error of calibration was 2.95% of the API level with a R2 of 0.991. Flowing blend powder spectra and API estimates showed variations consistent with those seen in model samples. The average values for flowing pharmaceutical blends were close to the API concentration, indicating that the proposed procedure was statistically acceptable. The model is considered very promising, and some improvements would lead to its final acceptance at production scale as a PAT tool.