title: Crystallization of D-mannitol in binary mixtures with NaCl: phase diagram and polymorphism.
abstract: OBJECTIVE
  To study the crystallization, polymorphism, and phase behavior of D-mannitol in binary mixtures with NaCl to better understand their interactions in frozen aqueous solutions.
  
  
  METHODS
  Differential scanning calorimetry, hot-stage microscopy, Raman microscopy, and variable-temperature X-ray diffractometry were used to characterize D-mannitol-NaCl mixtures.
  
  
  RESULTS
  NaCl and D-mannitol exhibited significant melt miscibility (up to 7.5% w/w or 0.20 mole fraction of NaCl) and a eutectic phase diagram (eutectic composition 7.5% w/w NaCl; eutectic temperature 150 degrees C for the alpha and beta polymorphs of D-mannitol and 139 degrees C for the delta). The presence of NaCl did not prevent mannitol from crystallizing but, depending on sample size, affected the polymorph crystallized: below 10 mg, delta was obtained; above 100 mg, alpha was obtained. Pure mannitol crystallized under the same conditions first as the delta polymorph and then as the a polymorph, with the latter nucleating on the former. KCl showed similar eutectic points and melt miscibility with D-mannitol as NaCl. LiCl yielded lower eutectic melting points, inhibited the crystallization of D-mannitol during cooling, and enabled the observation of its glass transition.
  
  
  CONCLUSIONS
  Despite their structural dissimilarity, significant melt miscibility exists between D-mannitol and NaCl. Their phase diagram has been determined and features polymorph-dependent eutectic points. NaCl influences the polymorphic behavior of mannitol, and the effect is linked to the crystallization of mannitol in two polymorphic stages.
authors.affiliation: College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Chitra
authors.initials: C
authors.lastname: Telang
authors.forename: Raj
authors.initials: R
authors.lastname: Suryanarayanan
authors.forename: Lian
authors.initials: L
authors.lastname: Yu
mesh_terms: D000465:Algorithms; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D005612:Freeze Drying; D008353:Mannitol / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013818:Thermogravimetry
chemical_list: D008353:Mannitol; D012965:Sodium Chloride