Impact of feed material properties on the milling of pharmaceutical ribbons: A PBM analysis.

Dry granulation is commonly used in the pharmaceutical industry for compressing heat and moisture sensitive feed materials into compacts, subsequently followed by milling. Population balance models (PBMs) are often used to explore the effects of milling conditions on the granule size distribution (GSD) but limited studies have investigated the effects of the feed material and ribbon properties on the resulting GSD. In this work, a variety of feed materials and ribbons with different mechanical properties were used to validate a mass-based bi-modal breakage function developed in a previous study (Olaleye et al., 2019). Ribbon like tablets (referred to as ribblets) with a range of precisely controlled porosities were produced using an Instron machine and pharmaceutical excipients including the microcrystalline cellulose MCC 101, MCC DG and a DCPA/MCC mixture. Roll compacted ribbons were also produced using MCC 102 and MCC DG excipients. The ribblets and ribbons were milled in an impact-dominated cutting mill and PBM parameters were obtained from the ribblet milling data. Mechanistic models related to the feed ribbon property were then developed. It was found that the PBM with the mass-based bi-modal breakage function can accurately predict the GSDs of both the milled ribblets and roll compacted ribbons. The model developed was successfully linked to ribbon properties such as porosity for the first time and the model parameter a that reflects the fines mode in the bi-modal breakage function increased linearly with ribblet porosity. This work demonstrates the versatility of the developed PBM and provides a systematic approach for describing the ribbon milling process.