Tuning the Kinetic Stability of the Amorphous Phase of the Chloramphenicol Antibiotic
We employ broadband dielectric spectroscopy to study the relaxation dynamics and crystallization kinetics of a broad-spectrum antibiotic, chloramphenicol, in its supercooled liquid form. Two dynamic processes are observed: the structural a relaxation, which becomes kinetically frozen at Tg = 302 ± 1...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| 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:2117/125730 |
| Acceso en línea: | https://hdl.handle.net/2117/125730 https://dx.doi.org/10.1021/acs.molpharmaceut.8b00786 |
| Access Level: | acceso abierto |
| Palabra clave: | Crystallization Supercooled drug molecular mobility crystallization kinetics chemical degradation dielectric spectroscopy polylactic acid Cristal·lització Àrees temàtiques de la UPC::Enginyeria química Àrees temàtiques de la UPC::Física |
| Sumario: | We employ broadband dielectric spectroscopy to study the relaxation dynamics and crystallization kinetics of a broad-spectrum antibiotic, chloramphenicol, in its supercooled liquid form. Two dynamic processes are observed: the structural a relaxation, which becomes kinetically frozen at Tg = 302 ± 1 K, and an intramolecular secondary relaxation. Under isothermal conditions, the supercooled drug displays interconversion between different isomers, followed by recrystallization. Recrystallization follows the Avrami law with Avrami exponent n = 1.3 ± 0.1, consistent with a one dimensional growth of crystalline platelets, as observed by electron microscopy. Exposure to humid atmosphere and subsequent heating to high temperature is found to degrade the compound. The partially degraded sample displays a much lower tendency to crystallize, likely because the presence of the degradation products results in spatial frustration. This sample exhibits enhanced conductivity and an additional relaxation, intermediate to the ones observed in the pure sample, which likely corresponds to the noncooperative dynamics of the main degradation product. We find that dispersing the antibiotic in polylactic acid results in an amorphous sample which does not crystallize at room temperature for relatively long times. |
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