Dehydration kinetics of neotame monohydrate

The dehydration of neotame monohydrate was monitored at various temperatures by differential scanning calorimetry (DSC), thermogravimetry (TGA), hot-stage microscopy (HSM), powder X-ray diffractometry (PXRD), and C-13 solid-state nuclear magnetic resonance (SSNMR) spectroscopy. This work emphasizes kinetic analysis of isothermal TGA data by fitting to various solid-state reaction models and by model-free kinetic treatment. The dehydration of neotame monohydrate follows the kinetics of a two-dimensional phase boundary reaction (R2) at 40-50degreesC with an activation energy of 75 +/- 9 kJ/mol, agreeing well with 60-80 kJ/mol from model-free kinetics. At a low heating rate in DSC and TGA, neotame monohydrate undergoes dehydration to produce anhydrate Form E, which then converts to anhydrate Form A, followed by the melting of A. Neotame monohydrate under dry nitrogen purge at 50 mL/min undergoes partial isothermal dehydration at 50degreesC to produce neotame anhydrate Form A. When neotame monohydrate is heated very slowly from 50 to 65-70degreesC over 24 h, pure Form A is obtained. C 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1423-1431, 2002.