Pneumatic Dry Granulation (PDG) in solid dosage form manufacture

E. Heilakka 1, P. Rahja 1, R. Lammens 2, N. Sandler 3 1 Atacama Labs, Helsinki, 2 University of Bonn, 3 Abo Akademi University, Pharmaceutical Sciences Purpose. Pneumatic dry granulation (PDG) is a novel dry granulation technology making use of conventional roller compaction by combining it with gas-flow based fractionation. This allows lower compaction forces to be used compared to standard dry granulation in order to preserve maximum reworkability of the granules. The purpose of this study was to compare the use of PDG and conventional roller compaction with a model high-dose metformin formulation. Methods. The PDG technology was compared with conventional roller compaction with Hosokawa Bepex Pharmapaktor using a model formulation consisting of metformin hydrochloride (80 % w/w) and microcrystallilline cellulose and maize starch. Five 500 g batches were produced with both technologies using five different roll pressures between the range 10-70 kN. The granules were assessed in terms of particle size, powder flow, tablet compression behavior, and physical end-product characteristics. Results. The results indicated that the PDG granules show significantly better flow properties than conventional RC granules. This can be explained by the efficient fractionation, which resulted in larger particle sizes with regard the PDG granules. The granule size distributions show that RC samples consisted of a substantial amount of fines compared to PDG granules. Similar PDG and RC granules possessed similar crushing strengths and disintegration times with similar compression forces used. In general, the weight variations (RSD %) were smaller for PDG granules indicating more consistent die filling during tabletting. Conclusion. The PDG technology proved to be capable of producing granules with improved downstream processability (especially powder flowability) compared to conventional roller compaction with all roll pressure forces used. The technology allowed the use of high-dose formulations without any processing complications.