Evaluation of the compaction of sulfathiazole polymorphs

The aim of this study was to relate the tableting performance assessed by an instrumented tableting machine to the mechanical properties measured by nanoindentation. Three different polymorphic forms of sulfathiazole were prepared by recrystallization, and the density and X‐ray powder diffraction patterns were measured and compared with theoretical density and simulated powder patterns, respectively. Tablets were prepared using a series of applied pressures, and the results were subjected to energy analysis, three dimensional (3D) modeling, and the traditional Heckel analysis. With these approaches, form I was found to be consistently the most brittle material, but the subtle differences between forms II and III were only revealed by 3D modeling. The rank order of the crushing force was found to be I ≌ II < III. From nanoindentation, form III was found to be much harder than forms I and II, and III also had a much higher Young's modulus. The energy calculations of the nanoindentation curves showed that form III was distinct from forms I and II, which is consistent with the presence of slip planes that are only present in form III. However, in this system, there was little correspondence between the macroscopic and microscopic measurements, and thus particle-particle interactions may to be of paramount importance. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:2111-2124, 2007