title: Comparison of molecular mobility in the glassy state between amorphous indomethacin and salicin based on spin-lattice relaxation times.
abstract: OBJECTIVE
  The purpose of the current study was to evaluate the molecular mobility of amorphous indomethacin and salicin in the relaxed glassy state based on spin-lattice relaxation times (T(1c)) and to clarify the effects of molecular mobility on their physical stability.
  
  
  METHODS
  Pulverized glassy amorphous indomethacin and salicin samples were completely relaxed, and the T(1c) values were investigated using solid-state (13)C-nuclear magnetic resonance (NMR) at temperatures below the glass transition temperature (T(g)). All NMR spectra were obtained using the T(1c) measurement method combined with variable-amplitude cross-polarization, the Torchia method, and total sideband suppression method.
  
  
  RESULTS
  The T(1c) value of amorphous indomethacin indicated that 73% of carbons were in a state of monodispersive relaxation, suggesting that the amorphous state was relatively homogeneous and restricted, particularly in backbone carbons. On the other hand, 92% of carbons of amorphous salicin exhibited both fast and slow biphasic relaxation. Individual structures of the salicin molecules behaved heterogeneously, and thus the entire molecule showed relatively fast local as well as slow mobility.
  
  
  CONCLUSIONS
  At temperatures below T(g), amorphous salicin had relatively greater molecular mobility than amorphous indomethacin. This difference in the molecular mobility of the two compounds is correlated with their crystallization behavior. Solid-state (13)C NMR provides valuable information on the physical stability of amorphous pharmaceuticals.
authors.affiliation: Department of Pharmaceutics, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan. Masuda.Katsuhiko@mk.m-pharma.co.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Masuda
authors.forename: Sachio
authors.initials: S
authors.lastname: Tabata
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sakata
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hayase
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yonemochi
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D001592:Benzyl Alcohols / Q000032:analysis* / Q000737:chemistry*; D002247:Carbon Isotopes; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005960:Glucosides; D007213:Indomethacin / Q000032:analysis / Q000737:chemistry*; D008968:Molecular Conformation; D009038:Motion; D011208:Powders; D013696:Temperature; D013997:Time Factors
chemical_list: D001592:Benzyl Alcohols; D002247:Carbon Isotopes; D005960:Glucosides; D011208:Powders; C005696:salicin; D007213:Indomethacin