Improving the prediction of exceptionally poor tableting performance: An investigation into Hiestand's “special case”

The mechanical and flow properties of selected pharmaceutical powdered excipients and drug substances were evaluated to investigate their behavior as extremely poor tableting, or “special case,” materials. The compaction stress, dynamic indentation hardness, and tensile strength of compacts compressed to 15% porosity and their powder's effective angle of internal friction were measured using the tableting indices technology and a simple shear cell, respectively. It has been previously demonstrated that compacts of special case materials exhibit a dynamic indentation hardness greater than the stress required to form the compact under slow compression conditions. In addition, new data suggest that special case materials also exhibit low compact dynamic indentation hardness, low compact tensile strength, and low powder effective angle of internal friction. These findings support the theory that the particles of such materials preferentially rearrange rather than deform under compressive conditions because bonding between them is weak. The added special case indicator measurements can be used to clearly identify exceptionally poor tableting powders during the selection of components for solid dosage formulations. Careful consideration of the data will provide guidance to the proper use of the bonding indices equations. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2017−2021, 2004