Developing a Virtual Flowability Sensor for Monitoring a Pharmaceutical Dry Granulation Line.

Current technologies to measure granule flowability involve at-line methods that can take hours to perform. This is problematic for a continuous dry granulation tableting line, where the quality assurance and control of the final tablet products depend on real-time monitoring and control of powder flowability. Hence, a real-time alternative is needed for measuring the flowability of the granular products coming out of the roller compactor, which is the unit operation immediately preceding the tablet press. Since particle analyzers have the potential to take inline measurements of the size and shape of granules, they can potentially serve as real-time flowability sensors, given that the size and shape measurements can be used to reliably predict flowability measurements. This paper reports on the use of Partial Least Squares (PLS) regression to utilize distributions of size and shape measurements in predicting the output of three different types of flowability measurements: rotary drum flow, orifice flow, and tapped density analysis. The prediction performance of PLS had a coefficient of determination ranging from 0.80 to 0.97, which is the best reported performance in the literature. This is attributed to the ability of PLS to handle high collinearity in the datasets and the inclusion of multiple shape characteristics-eccentricity, form factor, and elliptical form factor-into the model. The latter calls for a change in industry perspective, which normally dismisses the importance of shape in favor of size; and the former suggests the use of PLS as a better way to reduce the dimensionality of distribution datasets, instead of the widely used practice of pre-selecting distribution percentiles.