title: A solid-state NMR study of amorphous ezetimibe dispersions in mesoporous silica.
abstract: OBJECTIVE
  The purpose of this work is to examine the ability of methods based on multinuclear and multidimensional solid-state NMR (SSNMR) to perform detailed characterization of amorphous dispersions of ezetimibe adsorbed on mesoporous silica.
  
  
  METHODS
  Ezetimibe was loaded into two types of mesoporous silica with average pore sizes of 2.5 and 21 nm. The mesoporous materials were characterized by powder X-ray diffraction (PXRD), vibrational spectroscopy, differential scanning calorimetry, and (1)H, (13)C, (19)F, and (29)Si SSNMR analysis including relaxation time measurements. Interactions between the drug and silica were investigated using 1D and 2D SSNMR methods based on dipolar correlation using cross-polarization (CP) and spin diffusion.
  
  
  RESULTS
  PXRD was used to show the absence of crystalline ezetimibe in the mesoporous materials, and (19)F SSNMR was used to assess drug physical state and study mobility. (19)F-(29)Si CP methods were used to directly detect adsorbed ezetimibe. (1)H-(13)C, (1)H-(19)F, and (1)H-(29)Si, and heteronuclear correlation and (1)H homonuclear correlation experiments were used to investigate interactions between the drug and silica through (1)H environments.
  
  
  CONCLUSIONS
  SSNMR methods were able to detect interactions between the drug and the silica substrate. Differences between the drug loaded onto silica with two different pore sizes were observed, including differences in hydrogen bonding environment and molecular mobility. These methods should be useful for characterization of similar systems.
authors.affiliation: Product Development, GlaxoSmithKline plc., 709 Swedeland Road, King of Prussia, Pennsylvania 19406, USA. fvogt@morganlewis.com
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Vogt
authors.forename: Karen
authors.initials: K
authors.lastname: Roberts-Skilton
authors.forename: Sonya A
authors.initials: SA
authors.lastname: Kennedy-Gabb
mesh_terms: D000327:Adsorption; D000924:Anticholesteremic Agents / Q000737:chemistry*; D001384:Azetidines / Q000737:chemistry*; D003460:Crystallization; D000069438:Ezetimibe; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D016062:Porosity; D033362:Powder Diffraction; D012822:Silicon Dioxide / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D012822:Silicon Dioxide; D000069438:Ezetimibe