Consolidation mechanisms of pharmaceutical solids: a multi-compression cycle approach.

PURPOSE: The consolidation behavior of various pharmaceutical solids were characterized using compression-cycle profiles. Compression-cycle profiles for both uncompacted powder and formed tablets were obtained. These profiles were used to qualitatively and quantitatively characterize the consolidation mechanism of pharmaceutical solids.

METHODS: An Instron Universal Testing apparatus and a specially instrumented die coupled with a computerized data acquisition system were utilized to measure the upper-punch pressure and the corresponding die-wall pressure during the compression cycle.

RESULTS: Compression cycle profiles were obtained for a variety of pharmaceutical materials. Based on these profiles, parameters such as hysteresis areas, loading slopes, and unloading slopes were calculated for the materials studied.

CONCLUSIONS: Materials that consolidate by plastic deformation have similar compression cycle profiles for the first and subsequent compression cycles indicating that the plastic deformation process occurs to the same extent on the first as well as subsequent compression cycles. For brittle materials, the brittle fracture process occurs during the first compression cycle. During subsequent cycles the tabletted material does not undergo further yield or failure and primarily undergoes elastic deformation. Low molecular-weight polyethylene glycol is an excellent model material for plastically deforming materials, whereas sucrose or sodium citrate are excellent examples of materials that consolidate by brittle fracture.