Application of a compaction simulator to the design of a high-dose tablet formulation .1.

The compaction properties of an investigational drug are studied by the use of a compaction simulator. The effects of punch velocity over the range of 30-640 mm(-1) on the compaction properties of the pure drug and a variety of formulas incorporating a high dose of the active compound have been investigated. The data were analyzed by applying the Heckel equation. The pure drug was found to have a high yield pressure at a relatively low punch velocity of 31 mm(-1). As the punch velocity was increased there was a decrease in crushing strength, primarily as a result of increasing yield pressure. These findings indicate that the pure drug predominantly consolidated by fragmentation and elastic deformation, with a slow plastically deforming component. The information obtained on the consolidation mechanism of the pure drug and, subsequently, on model formulas were instrumental in the design and selection of a robust formula and granulation process. The advantages of conducting dosage form design and characterization studies during the early phase of tablet formulation using means such as a compaction simulator are emphasized in this investigation.