Compaction simulator studies of a new drug substance: effect of particle size and shape, and its binary mixtures with microcrystalline cellulose.

The compaction characteristics of a new drug substance with two crystal habits and particle size fractions as well as its binary mixtures with microcrystalline cellulose were studied using an integrated compaction research system under 300 and 450 MPa pressures. The results indicate that the drug substance has poor intrinsic compaction properties. The three-dimensional hexagonal crystal habit or smaller particle size consistently produced a slightly higher total work of compaction as compared with the cubic brick habit or larger particle size, respectively. However, neither crystal habit produced a coherent compact. The compactability of the drug substance was improved by the inclusion of microcrystalline cellulose, and the crushing strength of the compacts increased as the amount of microcrystalline cellulose in the binary mixture was increased. Such correlation was not observed when the compaction data were evaluated using either the Heckel equation or the percentage porosity change as a function of applied pressure.