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Artículo

Pharmaceutical polymorphism of a 5´-O-oxalatoyl prodrug of zidovudine (azidothymidine)

Kassuha, Diego EnriqueIcon ; Bruno, Flavia PaolaIcon ; Monti, Gustavo AlbertoIcon ; Sperandeo, Norma Rebeca
Fecha de publicación: 03/2020
Editorial: Open Science Publishers LLP
Revista: Journal of Applied Pharmaceutical Science
e-ISSN: 2231-3354
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Química Orgánica

Resumen

The importance of polymorphism in pharmaceuticals makes its study relevant. The aim of this study was to investigate the solid-state forms in which 3´-azido-2´,3´-dideoxi-5´-O-oxalatoyl-thymidinic acid (AZT-Ac), a zidovudine (AZT) prodrug with improved pharmacokinetic properties, may exist. Samples were prepared using different crystallization conditions, and characterized using powder X-ray diffraction, solid state nuclear magnetic resonance, differential scanning calorimetry, thermogravimetry and hot stage microscopy. Pharmaceutical relevant properties such as solid-state stability and intrinsic dissolution rate (IDR) at 37 °C in simulated gastric fluid (SGF) were also evaluated. AZT-Ac was found able to exist as a crystalline polymorph (AZT-Ac-C) and an amorphous phase (AZT-Ac-A), which were thoroughly characterized. At 40 °C/75% RH, AZT-Ac-A in part devitrified to AZT-Ac-C, and partially hydrolyzed to AZT after 7 and 14 days of storage, respectively. AZT-Ac-C was physically stable at 40 °C/75% RH but partly hydrolyzed to AZT after 14 days of storage. In SGF, AZT-Ac-C exhibited a linear ID profile and provided an ID rate of 0.494 mg/min/cm2 while AZT-Ac-A exhibited a nonlinear profile. Therefore, the crystalline form demonstrated advantages over the amorphous one in terms of solid state stability and IDR, but approaches to enhance its stability should be considered for further formulation of this prodrug.
Palabras clave: CRYSTALLIZATION , DIFFERENTIAL SCANNING CALORIMETRY , DRUGS , NUCLEAR MAGNETIC RESONANCE , NUCLEOSIDE INHIBITORS , X-RAY DIFFRACTIO
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/137095
URL: https://japsonline.com/abstract.php?article_id=3098&sts=2
DOI: http://dx.doi.org/10.7324/JAPS.2020.103008
Colecciones
Articulos(IFEG)
Articulos de INST.DE FISICA ENRIQUE GAVIOLA
Citación
Kassuha, Diego Enrique; Bruno, Flavia Paola; Monti, Gustavo Alberto; Sperandeo, Norma Rebeca; Pharmaceutical polymorphism of a 5´-O-oxalatoyl prodrug of zidovudine (azidothymidine); Open Science Publishers LLP; Journal of Applied Pharmaceutical Science; 10; 3; 3-2020; 67-74
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