title: Characterization of medicinal compounds confined in porous media by neutron vibrational spectroscopy and first-principles calculations: a case study with ibuprofen.
abstract: OBJECTIVE
  Amorphous formulations of ibuprofen were prepared by confining the drug molecules into the porous scaffolds. The molecular interactions between ibuprofen and porous media were investigated using neutron vibrational spectroscopy.
  
  
  METHODS
  Ibuprofen was introduced into the pores using sublimation and adsorption method. Neutron vibrational spectra of both neat and confined ibuprofen were measured, and compared to the simulated ibuprofen spectra using first-principles phonon calculations.
  
  
  RESULTS
  The neutron vibrational spectra showed marked difference between the neat crystalline and the confined ibuprofen in low-frequency region, indicating a loss of the overall structural order once the ibuprofen molecules were in the pores. Furthermore, the formation of ibuprofen dimers, which is found in the crystal structure, was greatly inhibited, possibly due to the preferential interactions between the carboxylic acid group of ibuprofen (-COOH) and the surface hydroxyl groups of porous scaffolds (Si-OH).
  
  
  CONCLUSIONS
  The experimental evidence suggests that, at the current drug loading, most, if not all, of the confined ibuprofen molecules were bound to the pore surfaces via hydrogen bonding. The structural arrangement of ibuprofen in the pores appears to be monolayer coverage. In addition, neutron vibrational spectroscopy is proven an exceedingly useful technique to study adsorbent-adsorbate interactions.
authors.affiliation: National Institute of Standards and Technology, NIST Center for Neutron Research, 100 Bureau Drive, Gaithersburg, Maryland 20899, USA. ken.qian@nist.gov
authors.forename: Ken K
authors.initials: KK
authors.lastname: Qian
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.forename: Terrence J
authors.initials: TJ
authors.lastname: Udovic
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D007052:Ibuprofen / Q000737:chemistry*; D008958:Models, Molecular; D009502:Neutrons; D033362:Powder Diffraction; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen