SOLID-STATE CHARACTERIZATION OF 2 POLYMORPHS OF ASPARTAME HEMIHYDRATE

From the known crystal structure of aspartame hemihydrate, designated form I, the theoretical powder X-ray diffraction (PXRD) pattern was ca lculated. This PXRD pattern differs significantly from that of the com mercially available aspartame hemihydrate, which is therefore a differ ent polymorph, designated form II. Form II transforms to form I during ball-milling or on heating for 30 min at 160 degrees C in the presenc e of steam. The two polymorphs were compared by PXRD, differential sca nning calorimetry, thermogravimetric analysis, Karl Fischer titrimetry , Fourier transform infrared (FTIR) absorption spectroscopy, C-13 soli d-state nuclear magnetic resonance (SSNMR) spectroscopy, scanning elec tron microscopy, particle size analysis, and measurements of true dens ity and intrinsic dissolution rate. Comparison of the C-13 SSNMR and F TIR spectra of the two polymorphs suggests that the crystal structure of form II is less symmetric, with the side chains located in multiple environments. Although both hemihydrate polymorphs on heating in the absence of moisture dehydrate to a crystalline anhydrate, form I does so at a lower temperature, suggesting weaker interactions of water wit h aspartame molecules. At higher temperatures the anhydrate from both hemihydrate polymorphs yields 3-(carboxymethyl)-6-benzyl-2,5-dioxopipe razine (DKP) by a cyclization reaction for which the temperature, reac tion enthalpy, and activation energy are very similar. Both hemihydrat e forms, when in contact with liquid water, yield the 2.5-hydrate.