Determination of breakage rate and breakage mode of roller compacted pharmaceutical materials

• Breakage rates of MCC and mannitol ribbons were measured.
• Rates were determined from mass throughput and the change in largest size class.
• Breakage rate did not depend on media fill level.
• Breakage rate was found to depend on impeller speed, mesh size, and porosity.
• Analysis of breakage rate can be used to estimate the breakage mode.

Roller compaction is a common unit operation in the manufacture of oral solid dose pharmaceutical products. The roller compactor can produce intermediate ribbons of compacted material that exhibit a range of mechanical properties. Both the breakage rate and the breakage mode of these intermediates will have an effect on the final particle size distribution (PSD), and are therefore important parameters in determining the performance of the final product in pharmaceutical manufacturing. The breakage rates of roller compacted ribbons of two pharmaceutical excipients, microcrystalline cellulose (MCC) and mannitol, were determined with two different approaches, i.e. by analysing the milling mass throughput and the change in mass in the largest granule size class. The self-similar solution of the breakage population balance equation provided an insight into size dependencies of breakage rates and the prevailing breakage mode for specific process parameters. The breakage rate was found to be dependent on the impeller speed, milling mesh aperture size and ribbon porosity, but not on grinding media fill level. For MCC ribbons the milling kinetic profile changed with the mesh aperture size, suggesting dependence of the breakage mode on screen size. Our work shows clear correlation between the amount of fines produced during milling and the underlying breakage mode. For the materials studied, it is evident that mannitol ribbons tend more toward an attrition breakage mode than MCC ribbons of equal porosity when milling with the same process settings.

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