Influence of particle size and shape on flowability and compactibility of binary mixtures of paracetamol and microcrystalline cellulose.

The influence of the size and shape of paracetamol particles on the flow and compression behavior of blends (1:1) of microcrystalline cellulose (MCC) was investigated. The effect of paracetamol particle shape was investigated by using two differently prepared samples, micronized and novel engineered Solution Atomization and Xstallization by Sonication (SAXS) particles, which exhibited similar particle size ranges (2-6 microm). The results were compared to data obtained for an untreated paracetamol sample. The blends containing SAXS particles exhibited increased bulk and tapped density and improved flow, compared to the blend containing micronized particles. This may reflect differences in shape since the SAXS particles exhibited spherical morphology. The compressibility of the blend containing untreated paracetamol was greater than blends containing the SAXS and micronized materials, which may reflect the different drug particle sizes and shapes. However, blends containing the needle-shaped particles of pure untreated sample, exhibited poor compactibility after storage at 10% RH. It was found that increasing the moisture content in the blends by storage at 44% RH resulted in an increase in the compactibility of the samples containing untreated and SAXS paracetamol with the blends containing micronized paracetamol being relatively unaffected. In general, tablets prepared from blends containing smaller particles of paracetamol exhibited significantly greater compactibility compared to tablets prepared containing the larger particle sized untreated paracetamol. The use of small, spherical drug particles may result in improvements in the bulk density, densification and compactibility of blends of paracetamol and microcrystalline cellulose.