To elucidate the compaction behavior of drug nanocrystals based composite particles (NP) during tabletting, the compaction behavior of binary mixtures of microcrystalline cellulose (MCC) and nanocrystal particles was investigated. The force-displacement correlation of mixtures containing different ratios of MCC and micronized NP was studied in order to explain the nature on densification of NP during compaction, and the resultant compaction curves (pressure as function of in-die thickness) were systemically analyzed to elucidate the most important mechanisms of volume reduction for MCC and NP in different stages of compaction. The results showed that the close compaction of individual MCC was relatively quickly achieved, and the drug NP particles could slide into the intrinsic void spaces between MCC microparticles. This was the reason that the particles size of MCC used in this study was significantly larger compared to that of drug NP. This interstitial rearrangement phenomenon of NP occurred on a typical time scale and was strongly dependent on the speed of compaction. This migration behavior occurred on void spaces of MCC inter-particles might be identified as an elastic stress relaxation mechanism and be helpful to dissolution of NP. MCC can effectively shield the NP from significant aggregation during compaction process.
Keywords: compaction; composite particles; interstitial rearrangement; microcrystalline cellulose; nanocrystals.