title: Neotame anhydrate polymorphs I: preparation and characterization.
abstract: OBJECTIVE
  To prepare, characterize, and compare polymorphs of neotame anhydrate.
  
  
  METHODS
  Neotame anhydrate polymorphs were prepared from amorphous or crystalline anhydrate by crystallization or suspension in various organic solvents, or by dehydration of neotame monohydrate. The following techniques were used for characterization: differential scanning calorimetry, thermogravimetry, hot-stage microscopy, powder X-ray diffractometry (PXRD), 13C solid-state nuclear magnetic resonance (SSNMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, dynamic water vapor sorption/desorption, and density measurements.
  
  
  RESULTS
  Seven polymorphs (Forms A-G) of neotame anhydrate were prepared and show different thermal properties and PXRD patterns. Two enantiotropically related pairs were identified: B and C; E and A. 13C SSNMR and FTIR spectroscopy clearly distinguish between Forms A, D, F, and G, which show similar needle-shaped morphology but distinct differences in dynamic water vapor sorption/desorption and density. The 13C SSNMR chemical shifts suggest conformational polymorphism. The stability in the presence of water vapor follows the rank order, G > A > D approximately = F, which resembles the rank orders of the molar volume and of the polarity of the solvents from which they crystallized.
  
  
  CONCLUSIONS
  The neotame anhydrate polymorphs appear to show different molecular conformations. The less dense polymorphic structures crystallize from solvents of greater polarity and sorb water vapor less rapidly and less completely. Two enantiotropic pairs were discerned.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455-0343, USA.
authors.forename: Zedong
authors.initials: Z
authors.lastname: Doug
authors.forename: Brian E
authors.initials: BE
authors.lastname: Padden
authors.forename: Jonathon S
authors.initials: JS
authors.lastname: Salsbury
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Munson
authors.forename: Steve A
authors.initials: SA
authors.lastname: Schroeder
authors.forename: Indra
authors.initials: I
authors.lastname: Prakash
authors.forename: David J W
authors.initials: DJ
authors.lastname: Grant
mesh_terms: D000812:Anhydrides / Q000138:chemical synthesis / Q000737:chemistry; D003460:Crystallization; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000812:Anhydrides; D004151:Dipeptides; C404525:neotame