Serena Schiano, Chuan-Yu Wu, Andreja Mirtic, Gavin Reynolds

Dry granulation using roll compaction (DGRC) becomes increasingly adopted in the pharmaceutical industry due to its unique advantage of not requiring liquid binder and a subsequent drying process. However the DGRC process presents also some challenges, in particular, high fine fraction generated during the milling stage significantly limits its application. Although the fines produced can be recycled in practice, it may lead to poor content uniformity of the final product. At present there is a lack of mechanistic understanding of milling of roll compacted ribbons. For instance, it is not clear how fines are generated, what are the dominant mechanisms and controlling attributes and if any measurement technique can be used to characterise ribbon milling behaviour. Therefore, the aim of this paper was to assess if ribbon milling behaviour can be assessed using some characterization methods. For this purpose, friability was evaluated for ribbons made of microcrystalline cellulose (MCC) powders using a friability tester that was originally developed for characterising the tendency of pharmaceutical tablets to generate small pieces while being abraded. Granules were also produced by milling of the ribbons and their size distributions were analysed. The correlation between the fine fraction of the granules with ribbon friability was then explored. It was found that there was a strong correlation between ribbon friability and the fine fraction of granules generated during milling. This implies that friability tests can be performed to characterise ribbon milling behaviour, and ribbon friability provides a good indication of the fraction of fines generated during ribbon milling.