Nose temperature and anticorrelation between recrystallization kinetics and molecular relaxation dynamics in amorphous morniflumate at high pressure

We probe the dielectric response of the supercooled liquid phase of Morniflumate, a drug with anti-inflammatory and antipyretic properties, studying in particular the pressure and temperature dependence of the relaxation dynamics, glass transition temperature Tg, and recrystallization kinetics. Tg i...

Descripción completa

Detalles Bibliográficos
Autores: Romanini, Michela|||0000-0002-1685-855X, Valenti, Sofia, Barrio Casado, María del|||0000-0003-3467-7581, Tamarit Mur, José Luis|||0000-0002-7965-0000, Macovez, Roberto|||0000-0001-5026-9372, Rodríguez Martín, Sergio
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/179466
Acceso en línea:https://hdl.handle.net/2117/179466
https://dx.doi.org/10.1021/acs.molpharmaceut.9b00351
Access Level:acceso abierto
Palabra clave:Molecular dynamics
Crystallization
Glassy drug stability
Dielectric spectroscopy
Secondary relaxation
Recrystallization kinetics
Optimum crystal growth temperature
Cristal·lització
Dinàmica molecular
Àrees temàtiques de la UPC::Física
Descripción
Sumario:We probe the dielectric response of the supercooled liquid phase of Morniflumate, a drug with anti-inflammatory and antipyretic properties, studying in particular the pressure and temperature dependence of the relaxation dynamics, glass transition temperature Tg, and recrystallization kinetics. Tg increases by roughly 20 K every 100 MPa at low applied pressure, where the ratio Tg/Tm has a constant value of ~0.8 (Tm = melting point). Liquid Morniflumate displays two dielectric relaxations: the structural a relaxation associated with the collective reorientational motions, which become arrested at Tg, and a secondary relaxation likely corresponding to an intramolecular dynamics. The relaxation times of both processes scale approximately with the inverse reduced temperature Tg/T. Near room temperature and under an applied pressure of 50 MPa, supercooled Morniflumate recrystallizes in a characteristic time of few hours, with an Avrami exponent of 1.15. Under these conditions, the recrystallization rate is a nonmonotonic function of temperature, displaying a maximum at around 298 K, which can be taken to be the optimum crystal growth temperature Tnose. The ß relaxation becomes kinetically frozen at ambient temperature under an applied hydrostatic pressure higher than 320 MPa, suggesting that the Morniflumate glass should be kinetically stable under these conditions.