IMPACT OF EXCIPIENT PARTICLE SIZE DISTRIBUTION VARIABILITY ON POWDER RHEOLOGY AND MIXING

Abstract

The impact of particle size distribution (PSD) variability, in excipients, on solids mixing is underexplored. Resultantly, manufacturers rely on raw material control and over-processing to avoid risks - which is problematic. This project strived to uncover how and why PSD variability affects mixing; and implement an automated robust mixing operation. Lactose, which exhibited commercially-encountered PSD variability, was mixed with chlorpheniramine and microcrystalline cellulose. The effects of PSD variability on mixing were analysed. Avalanche flow characterisation, coupled with multivariate image analysis, was performed to uncover mechanisms. Near infrared spectroscopy was adopted for in-line PSD and blend homogeneity characterisation, for feedforward and feedback control in an automated robust mixing operation. Results showed PSD variability affected mixing. Due to rheological variations, the optimal rotation speed differed with PSD. Automated mixing operation successfully modulated mixing for time-efficiency. Findings yield knowledge and tools to enhance robustness in mixing, which align manufacturing practice with regulatory expectations.