Impact of sonocrystallization and milling on the flow properties

Paracetamol (PCM) form I (monoclinic), is a thermodynamically stable form. It is well known that form I (commercial form) of PCM exhibits poor tableting properties due to lack a of slip planes in its crystal structure [1]. Many techniques of crystal engineering have been used with an aim of improving physical and mechanical properties but have achieved only limited success. The particle size distribution of an active pharmaceutical ingredient (API) can directly influence properties such as compaction, flow and dissolution. Particle size distribution depends on the milling conditions to which the API is exposed. The aim of this project was to investigate how wet milling (WM) and dry milling (DM) affects solid state characteristics, particle size distribution and flow properties of PCM. Particle size distribution and flow properties were also compared with crystals produced using ultra sonication (US), which is considered as good technique to narrow the particle size distribution [2, 3]. Wet and dry milling was performed using a Quadro Comil. Laser diffraction was used to analyse particle size distribution, and powder rheometry was used to investigate the flow properties. Dry milling resulted in smaller size in comparison to wet milling when the same parameters were used for both processes (Fig 1a). Agglomeration is likely to be the reason for this variation in size between wet and dry milled samples. An inspection of the span values indicated that the sonocrystallized sample exhibits a narrower particle size distribution when compared with dry milled and wet milled crystals (Fig 1a). The advantage of sonocrystallization over wet and dry milling is demonstrated by the narrower particle size distribution (lower span values) and better flow properties (low cohesion and higher flow function) (Fig 1b). These results indicate that sonocrystallization, would be a better option than dry milling and wet milling to facilitate particle size optimization with subsequent improvement in the particle size distribution and flow properties of PCM. ACKNOWLEDGMENT This work has been supported by Science Foundation Ireland and SSPC (grant number: 12/RC/2275).