title: Solid-state characterization of two polymorphs of aspartame hemihydrate.
abstract: From the known crystal structure of aspartame hemihydrate, designated form 1, the theoretical powder X-ray diffraction (PXRD) pattern was calculated. This PXRD pattern differs significantly from that of the commercially available aspartame hemihydrate, which is therefore a different 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 presence of steam. The two polymorphs were compared by PXRD, differential scanning calorimetry, thermogravimetric analysis, Karl Fischer titrimetry, Fourier transform infrared (FTIR) absorption spectroscopy, 13C solid-state nuclear magnetic resonance (SSNMR) spectroscopy, scanning electron microscopy, particle size analysis, and measurements of true density and intrinsic dissolution rate. Comparison of the 13C SSNMR and FTIR 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 with aspartame molecules. At higher temperatures the anhydrate from both hemihydrate polymorphs yields 3-(carboxymethyl)-6-benzyl-2,5-dioxopiperazine (DKP) by a cyclization reaction for which the temperature, reaction enthalpy, and activation energy are very similar. Both hemihydrate forms, when in contact with liquid water, yield the 2.5-hydrate.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455-0343, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Leung
authors.forename: B E
authors.initials: BE
authors.lastname: Padden
authors.forename: E J
authors.initials: EJ
authors.lastname: Munson
authors.forename: D J
authors.initials: DJ
authors.lastname: Grant
mesh_terms: D001218:Aspartame / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D017550:Spectroscopy, Fourier Transform Infrared; D013549:Sweetening Agents / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D013549:Sweetening Agents; D001218:Aspartame