Detecting Blending End-Point Using Mean Squares Successive Difference Test and Near-Infrared Spectroscopy

An algorithm based on mean squares successive difference test applied to near-infrared and principal component analysis scores was developed to monitor and determine the blending profile and to assess the end-point in the statistical stabile phase. Model formulations consisting of an active compound (acetylsalicylic acid), together with microcrystalline cellulose and two grades of calcium carbonate with dramatically different particle shapes, were prepared. The formulation comprising angular-shaped calcium carbonate reached blending end-point slower when compared with the formulation comprising equant-shaped calcium carbonate. Utilizing the ring shear test, this distinction in end-point could be related to the difference in flowability of the formulations. On the basis of the two model formulations, a design of experiments was conducted to characterize the blending process by studying the effect of CaCO3 grades and fill level of the bin on blending end-point. Calcium carbonate grades, fill level, and their interaction were shown to have a significant impact on the blending process