title: Toward a Better Understanding of the Physical Stability of Amorphous Anti-Inflammatory Agents: The Roles of Molecular Mobility and Molecular Interaction Patterns.
abstract: The aim of this article is to examine the crystallization tendencies of three chemically related amorphous anti-inflammatory agents, etoricoxib, celecoxib, and rofecoxib. Since the molecular mobility is considered as one of the factors affecting the crystallization behavior of a given material, broadband dielectric spectroscopy was used to gain insight into the molecular dynamics of the selected active pharmaceutical ingredients. Interestingly, our experiments did not reveal any significant differences in their relaxation behavior either in the supercooled liquid or in the glassy state. Hence, as a possible explanation for the enhanced physical stability of etoricoxib, its ability to undergo a tautomerization reaction was recognized. The occurrence of intramolecular proton transfer in the disordered etoricoxib was proven experimentally by time-dependent dielectric and infrared (IR) measurements. Additionally, IR spectroscopy combined with density functional theory calculations pointed out that in the etoricoxib drug, being in fact a binary mixture of tautomers, the individual isomers may interact with each other through a hydrogen bonding network. A possible explanation of this issue was achieved by performing dielectric experiments at elevated pressure. Since compression results in etoricoxib recrystallization, the possible influence of pressure on the observed stabilization effect is also carefully discussed.
authors: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: M
authors: M
authors: Rams-Baron
authors: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: Z
authors: Z
authors: Wojnarowska
authors: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: K
authors: K
authors: Grzybowska
authors: Institute of Material Sciences, University of Silesia , 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: M
authors: M
authors: Dulski
authors: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: J
authors: J
authors: Knapik
authors: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: K
authors: K
authors: Jurkiewicz
authors: Department of Otolaryngology, Silesian Medical University , Francuska 20/27, 40-027 Katowice, Poland.
authors: W
authors: W
authors: Smolka
authors: Department of Physical Chemistry, Medical University of Gdansk , Hallera 107, 84-416 Gdansk, Poland.
authors: W
authors: W
authors: Sawicki
authors: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: A
authors: A
authors: Ratuszna
authors: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: M
authors: M
authors: Paluch
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D000068579:Celecoxib / Q000737:chemistry*; D003460:Crystallization; D058266:Dielectric Spectroscopy; D004355:Drug Stability; D000077613:Etoricoxib; D007783:Lactones / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D013450:Sulfones / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D007783:Lactones; D011725:Pyridines; D013450:Sulfones; C116926:rofecoxib; D000068579:Celecoxib; D000077613:Etoricoxib
keywords: amorphous drug; hydrogen bonding; molecular dynamics; molecular interactions; physical stability; tautomerization