Mixture Experiments on Roll Compaction
Part 1
Ralf Grulkea, Peter Kleinebuddeb, and George Shlieoutc
School of Pharmacy, Institute of Pharmaceutics and Biopharmaceutics, Martin Luther-University Halle-Wittenberga, Halle/Saale, Institute of Pharmaceutics and Biopharmaceutics,
Heinrich Heine-University Düsseldorfb, Düsseldorf, and Solvay Pharmaceuticals GmbHc, Hannover (Germany)
Three substances and mixtures of these materials were compacted at two different specific compaction forces in a roll compactor and the ribbons were granulated under constant conditions. The received granules were analysed regarding bulk density, tapped density, flowability, amount of fines and quartiles of particle size distribution. The used materials are microcrystalline cellulose (MCC), lactose monohydrate (LM) and dicalcium phosphate dihydrate (DCPD).
A higher specific compaction force resulted in higher bulk and tapped densities, lower amounts of fines, higher particle sizes and better flow rates for all compositions. Bulk and tapped density of the mixtures were directly proportional to the composition of the mixture. However, in the presence of MCC other granule characteristics deviated from a direct proportionality to the composition of the mixture. For mixtures including MCC, the amount of fines was higher and the corresponding quartiles of the particle size distribution were lower compared to the expected value calculated from the pure components.
These facts led to the hypothesis that MCC as the material with the lowest yield pressure encloses the other materials with a higher yield pressure. During granulation proceß the enclosed material would appear in a higher proportion within the amount of fines. First analyses corroborate this hypothesis.
Key words Dicalcium phosphate dehydrate • Dry granulation • Granules, mixtures • Lactose monohydrate • Microcrystalline cellulose • Roll compaction
