Breakage, temperature dependency and contamination of Lactose during ball milling in ethanol

• Particle morphology depends on stabilization additives and processing temperature.
• Recrystallization effects shown in planetary ball mill, tempered ball mill and stirred media mill.
• Breakage behaviour of Lactose particles in ethanol suspension.
• Low product contamination while mill operated at optimum stress energy.
• High production rate and low product contamination received with high solids contents.

Wet stirred media milling is an established method for the production of drug nanoparticles which are increasing the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). While the processability of various organic materials has been proved in aqueous suspensions, this work focuses on the milling of the organic substance Lactose in ethanol. The aim of this study was the comparison of these results with the former studies in stirred media mills with organic materials in water as well as the analysation of recrystallization processes induced by increasing suspension temperature. Regarding the milling performance different grinding media materials as well as sizes, stirrer tip speeds and the solids contents of the suspension were varied. Furthermore the amount of generated product contamination was measured and a correlation to the process parameters and the used grinding beads was analysed. A convincing valuation of the milling results is only possible if there are no agglomeration effects in the suspensions. Therefore, at the beginning a stabiliser screening with different ionic and non-ionic additives was performed in a planetary ball mill. This showed an effect of the process temperature on the recrystallization behaviour of the particles and, thus, the final product fineness and particle shapes what was furthermore confirmed by milling the Lactose under controlled conditions in a stirred media mill.

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