title: Structural characterization and aging of glassy pharmaceuticals made using acoustic levitation.
abstract: Here, we report the structural characterization of several amorphous drugs made using the method of quenching molten droplets suspended in an acoustic levitator. (13) C NMR, X-ray, and neutron diffraction results are discussed for glassy cinnarizine, carbamazepine, miconazole nitrate, probucol, and clotrimazole. The (13) C NMR results did not find any change in chemical bonding induced by the amorphization process. High-energy X-ray diffraction results were used to characterize the ratio of crystalline to amorphous material present in the glasses over a period of 8 months. All the glasses were stable for at least 6 months except carbamazepine, which has a strong tendency to crystallize within a few months. Neutron and X-ray pair distribution function analyses were applied to the glassy materials, and the results were compared with their crystalline counterparts. The two diffraction techniques yielded similar results in most cases and identified distinct intramolecular and intermolecular correlations. The intramolecular scattering was calculated based on the crystal structure and fit to the measured X-ray structure factor. The resulting intermolecular pair distribution functions revealed broad-nearest and next-nearest neighbor molecule-molecule correlations. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1290-1300, 2013.
authors: X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Illinois 60439, USA. benmore@anl.gov
authors: Chris J
authors: CJ
authors: Benmore
authors: J K R
authors: JK
authors: Weber
authors: Amit N
authors: AN
authors: Tailor
authors: Brian R
authors: BR
authors: Cherry
authors: Jeffery L
authors: JL
authors: Yarger
authors: Qiushi
authors: Q
authors: Mou
authors: Warner
authors: W
authors: Weber
authors: Joerg
authors: J
authors: Neuefeind
authors: Stephen R
authors: SR
authors: Byrn
mesh_terms: D000162:Acoustics; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D033362:Powder Diffraction; D014961:X-Ray Diffraction
chemical_list: D004364:Pharmaceutical Preparations