Abstract
Dry granulation is commonly used in the pharmaceutical industry to compress powders into compacts (e.g. ribbons) followed by milling of ribbons into granules with pre-defined size distributions (GSDs). One of the major challenges associated with ribbon production and ribbon milling processes is that the undesirable interactions between diverse process variables (e.g. roll compactor/mill designs and operating conditions) and the feed material properties can often result in the production of large amount of fines. Consequently, to produce granules with the desired attributes, it is crucial to optimise both the ribbon production and ribbon milling processes for a given feed material. The significance of the feed screw speed and roll speed during ribbon production was highlighted in recent publications but the synergetic effects of these parameters on ribbon porosity was rarely examined. However, in this thesis, the impact of the screw-to-roll speed ratio was investigated and the resultant ribbons were characterised. Since the interactions between process variables and feed materials can significantly influence the resultant ribbon and granule properties, it is therefore vital to develop models such as population balances that can predict the GSDs from ribbon milling, However, limited population balance models (PBMs) in the literature have investigated the effects of ribbon properties during ribbon milling. So this thesis presents the bimodal GSDs obtained experimentally from ribbon milling and these GSDs were simulated using a population balance model (PBM) coupled with a new breakage function. Additionally, a thorough understanding of the breakage of single compacts (e.g. tablets) can potentially unravel the complex interactions that exist between process variables and the feed materials. However, limited studies in the literature have examined the breakage of single pharmaceutical compacts. So in this thesis, single tablets produced from diverse pharmaceutical materials and with different porosities and thicknesses were subjected to impact breakage in a custom-built air gun for the first time and the tablet breakage phenomena were analysed using an ultrahigh-speed camera. Therefore, the work in this thesis provides the fundamental understanding that can be used to describe the breakage behaviour of different pharmaceutical compacts. Furthermore, the compact breakage phenomena and predictive models discussed in this work can potentially aid the optimisation and improvement of the pharmaceutical ribbon milling process.