Compaction of crystallographic forms of pharmaceutical granular lactoses. I. Compressibility

Physico-chemical properties of a substance including the compaction behaviour are directly connected with the crystalline structure. The aim of this work is to compare the compaction behaviour in a group of excipient and in this first part, to display the influence of lactose structures on the compressibility. alpha-Lactose monohydrate (LalphaM), anhydrous beta-lactose (LbetaA), anhydrous alpha-lactose (LalphaA) and partly amorphous lactose (FF) were compressed using instrumented presses to investigate the densification behaviour under pressure. Force-displacement curves were associated to two energy parameters, specific cycle energy and specific expansion energy. This approach was used to class the four lactose species. It is possible to differentiate three groups with the specific energy cycle, FF, LalphaA/LbetaA and LalphaM in decreasing order of this energy. At the same time, the values of specific expansion energy are relatively low for FF and LalphaA contrary to LalphaM and LbetaA. Then, Heckel's plots were obtained with two compact geometries and the mean yield pressure was calculated from the in-die-method and the out-of-die-method. Two lactoses seem to differ, LalphaM appears to be the most ductile whereas LalphaA is more brittle than the others. Finally, it is concluded, that in the case of lactoses, pseudopolymorphism seems to affect the compressibility more than anomerisation or partial amorphisation. (C) 2004 Elsevier B.V. All rights reserved.