title: The Slow Relaxation Dynamics in the Amorphous Pharmaceutical Drugs Cimetidine, Nizatidine, and Famotidine.
abstract: The slow molecular mobility in the amorphous solid state of 3 active pharmaceutical drugs (cimetidine, nizatidine, and famotidine) has been studied using differential scanning calorimetry and the 2 dielectric-related techniques of dielectric relaxation spectroscopy and thermally stimulated depolarization currents. The glass-forming ability, the glass stability, and the tendency for crystallization from the equilibrium melt were investigated by differential scanning calorimetry, which also provided the characterization of the main relaxation of the 3 glass formers. The chemical instability of famotidine at the melting temperature and above it prevented the preparation of the amorphous for dielectric studies. In contrast, for cimetidine and nizatidine, the dielectric study yielded the main kinetic features of the α relaxation and of the secondary relaxations. According to the obtained results, nizatidine displays the higher fragility index of the 3 studied glass-forming drugs. The thermally stimulated depolarization current technique has proved useful to identify the Johari-Goldstein relaxation and to measure τβJGin the amorphous solid state, that is, in a frequency range which is not easily accessible by dielectric relaxation spectroscopy.
authors: Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors: M Teresa
authors: MT
authors: Viciosa
authors: Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors: Joaquim J
authors: JJ
authors: Moura Ramos
authors: Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal. Electronic address: hdiogo@tecnico.ulisboa.pt.
authors: Hermínio P
authors: HP
authors: Diogo
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002927:Cimetidine / Q000737:chemistry* / Q000378:metabolism; D015738:Famotidine / Q000737:chemistry* / Q000378:metabolism; D016567:Nizatidine / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors
chemical_list: D015738:Famotidine; D002927:Cimetidine; D016567:Nizatidine
keywords: DRS; DSC; TSDC; amorphous pharmaceuticals; cimetidine; dynamic fragility; famotidine; nizatidine