Artículo
Early stages of drug crystallization from amorphous solid dispersion via fractal analysis based on chemical imaging
Autor/es | Abreu Villela, Renata
Schönenberger, Monica Caraballo Rodríguez, Isidoro Kuentz, Martin |
Departamento | Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica |
Fecha de publicación | 2018-12 |
Fecha de depósito | 2024-04-04 |
Publicado en |
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Premios | Premio Mensual Publicación Científica Destacada de la US. Facultad de Farmacia |
Resumen | Early stages of crystallization from amorphous solid dispersion (ASD) are typically not detected by means of standard methods like powder X-ray diffraction (XRPD). The aim of this study is therefore to evaluate if fractal ... Early stages of crystallization from amorphous solid dispersion (ASD) are typically not detected by means of standard methods like powder X-ray diffraction (XRPD). The aim of this study is therefore to evaluate if fractal analysis based on energy dispersive X-ray imaging can provide the means to identify early signs of physical instability. ASDs of the poorly water-soluble compound, felodipine (FEL) were prepared by solvent evaporation using different grades of HPMCAS, at 50 wt% drug loading. Samples were stored at accelerated conditions of 40 °C. Scanning electron microscopy equipped with an energy-dispersive X-ray spectroscopy (SEM-EDS) was used for elemental mapping of tablet surfaces. Comparative data were generated with a standard XRPD and with more sensitive methods for detection of early instability, i.e. laser scanning confocal microscopy (LSM) and atomic force microscopy (AFM). The SEM-EDS identified changes of drug-rich domains that were confirmed by LSM and AFM. Early changes in drug clusters were also revealed by a multifractal analysis that indicated a beginning phase separation and drug crystallization. Therefore, the presented fractal cluster analysis based on chemical imaging bears much promise as a new method to detect early signs of physical instability in ASD, which is of great relevance for pharmaceutical development. |
Agencias financiadoras | Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior. Brasil Ministerio de Economía y Competitividad (MINECO). España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) |
Identificador del proyecto | 99999.001486
MAT2016-77345-C3-3-P |
Cita | Abreu Villela, R., Schönenberger, M., Caraballo Rodríguez, I. y Kuentz, M. (2018). Early stages of drug crystallization from amorphous solid dispersion via fractal analysis based on chemical imaging. European Journal of Pharmaceutics and Biopharmaceutics, 133, 122-130. https://doi.org/10.1016/j.ejpb.2018.10.007. |
Ficheros | Tamaño | Formato | Ver | Descripción |
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10.1016j.ejpb.2018.10.007.pdf | 489.0Kb | [PDF] | Ver/ | Versión aceptada |
Figures_final_RAV sent.xlsx | 6.046Mb | [Microsoft Excel 2007] | Ver/ | Figuras |