Monitoring of Blend Uniformity and Drug Concentration Using NIR Spectroscopy in a Continuous Mixing Process

A non-invasive NIR spectroscopic method was used to obtain in-line spectra of a continuous mixing process for pharmaceutical blends. The mixing performance and flow behavior were studied. Partial least squares (PLS) calibration models were constructed to predict the active pharmaceutical ingredient (API) concentration within the blend in real time. A design of experiments (DOE) varying the API concentration [acetaminophen - APAP] over the range of 0 to 15% (w/w) was used. Mixing performance was characterized by the relative standard deviation (RSD) of scanned powder flowing through an optical window mounted on a chute. The flow behavior was analyzed with the residence time distribution (RTD). Mixing performance was observed to produce RSD’s between 5-9% which was highly affected by the APAP concentration. As APAP concentration increased, its cohesive properties made the powder to adhere to the NIR window thus affecting the spectral data acquisition. Residence time distributions showed that as flow rate and rotation rate increased the mean residence time decreased affecting blend homogeneity significantly. As a result, intermediate flow rates and rotation rates showed the best mixing performance.