"Soft tableting": a new concept to tablet pressure-sensitive materials.

The aim of this study was to confirm the hypothesis that tableting using excipients with greater elastic deformation results in improved performance of pressure-sensitive drugs relative to the excipients with low elastic deformation. Tableting with highly elastic deforming excipients and the resultant minimization of the process damage is referred to in this article as "soft tableting." Carrageenans, chitosans, and polyethylene oxides were tested as potentially useful tableting excipients. alpha-Amylase, amorphous indomethacin, theophylline monohydrate, and enteric-coated pellets were used as models for pressure-sensitive materials. Three-dimensional modeling of the tableting data and elastic recovery of the tablets were the tools for mechanical characterization. The crushing force of the tablets was analyzed. Inactivation of alpha-amylase was determined by using the starch iodine reaction method. Pseudopolymorphic and polymorphic changes were analyzed using Fourier transform (FT) Raman spectroscopy. The effects of pressure on the integrity of the pellets were tested by release studies and scanning electron microscopy. The process of tablet formation was characterized for potentially useful tableting excipients. The results were compared with the results of traditional excipients as microcrystalline cellulose (MCC), dicalcium phosphate dihydrate, and hydroxypropyl methylcellulose (HPMC). A ranking order for soft tableting was deduced from the mechanical properties. The tableting excipients were ranked according to their general plasticity (GP): GP(carrageenans)<GP(chitosans)<GP(MCC)<GP(HPMC)<GP(polyethylene oxides). This theoretical order of suitability has been experimentally proven to be valid for the pressure-sensitive materials. In conclusion, the new concept for soft tableting is valid.