Particle Design of Tolbutamide by the Spherical Crystallization Technique: V: Improvement of Dissolution and Bioavailability of Direct Compressed Tablets Prepared Using Tolbutamide Agglomerated Crystals

Abstract

Tolbutamide (TBM) agglomerated crystals were prepared by three spherical crystallization techniques, the solvent change (SC) method, neutralization (NT) method and quasi-emulsion solvent diffusion (QESD) method (SC-A, SC-B, NT and QESD agglomerated crystals), followed by mixture with a disintegrating agent and a lubricant (physical mixtures), and then tableting by the direct compression method. Unagglomerated TBM original crystals (bulk) were treated in the same manner. The dissolution rate and bioavailability of TBM from the physical mixtures and tablets were evaluated to look for a correlation between the in vitro dissolution profile and in vivo bioavailability. The TBM dissolution rate from the physical mixtures and tablets increased in the order of bulk QESD < SC-A < SC-B