Mechanistic approach in powder blending PAT: Bi-layer mixing and asymptotic end point prediction

Abstract

We derive a simple first order kinetics model for the powder mixing in a bin blender and adapt it to fit the NIR spectra obtained during the real-time mixing. The model is tested on a full drug product formulation mixing consisting of API and multiple excipients. It allows to extract a quantitative mixing rate for individual ingredients, which may be used in the drug development and production scale-up design. We further propose an algorithm for a calibration-free blending end-point determination from the NIR data, which allows for a robust and easily transferable blending process control.