The continuous feeding-mixing system ensures the composition uniformity down to the tableting continuous manufacturing line so that a quality end-product is consistently delivered. Near-infrared spectroscopy (NIRS) enables in-line assessment of the blend's critical quality attributes in real-time. In this study, the effect of total feed rate and impeller speed on the continuous blending process monitored in-line by NIRS was examined by principal component analysis (PCA), ANOVA simultaneous component analysis (ASCA) and partial least squares (PLS) regression. Process data were generated by a factorial experimental design with process parameters and a constant formulation comprised of: 30 % (wt/wt) ibuprofen, 67.5 % (wt/wt) microcrystalline cellulose, 2 % (wt/wt) of sodium starch glycolate and 0.5 % (wt/wt) of magnesium stearate. The PCA hinted at the prevalence of impeller speed effect on ibuprofen concentration due to path length variation of the NIR light caused by the fluidized behaviour in the powder blend as a result of high speed ranges (>300 rpm). The ASCA model indicated that while both impeller speed and total feed rate effects were statistically significant (p-value=0.004), the impeller speed was the factor that contributed the most to the spectral variance (55.5 %). The PLS regression model for the ibuprofen content resulted in a RMSECV of 1.3 % (wt/wt) and showed that impeller speed was yet again the factor that exerted the major influence on spectral variance, owing to its wavelength-dependent effect that prevents common pre-processing techniques from eliminating it across the entire NIR range. The best sample presentation to the NIR probe was achieved at low impeller speed ranges (<600 rpm) and low total feed rates (<15 kg/h), such that it enhanced the PLS model ability to predict the ibuprofen concentration in the blend.
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