Role of microstructure in drug release from chitosan amorphous solid dispersions

The unexpected dissolution behaviour of amorphous diflunisal-chitosan solid dispersions (kneading method) with respect to the crystalline co-evaporated systems is the starting point of this research. This work is an in-depth study of the diflunisal release behaviour from either chitosan or carboxyme...

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Detalles Bibliográficos
Autores: Lucio, D. (David)|||/items/3ce7e252-82c0-4571-a2b9-c7d313337463, Zornoza, A. (Arantza)|||/items/171a1c4a-646c-4982-b6fe-30b0140d422a, Martínez-Oharriz, M. (María Cristina)|||/items/05dc7a92-e9c7-4839-8f0b-fb5104a3e43e
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/113121
Acceso en línea:https://hdl.handle.net/10171/113121
Access Level:acceso abierto
Palabra clave:amorphous solid dispersión
drug reléase
microstructure
diflunisal
chitosan
carboximethylchitosan
Descripción
Sumario:The unexpected dissolution behaviour of amorphous diflunisal-chitosan solid dispersions (kneading method) with respect to the crystalline co-evaporated systems is the starting point of this research. This work is an in-depth study of the diflunisal release behaviour from either chitosan or carboxymethylchitosan dispersions. The microstructure is not usually considered when designing this type of products; however, it is essential to understand the process of solvent penetration and subsequent drug release through a polymeric system, as has been evidenced in this study. In accordance with the kinetic data analysed, it is possible to conclude that the porous structure, conditioned by the sample preparation method, can be considered the main factor involved in diflunisal release. The low mean pore size (1–2 µm), low porosity, and high tortuosity of the amorphous kneaded products are responsible for the slow drug release in comparison with the crystalline coevaporated systems, which exhibit larger pore size (8–10 µm) and lower tortuosity. Nevertheless, all diflunisal-carboxymethylchitosan products show similar porous microstructure and overlapping dissolution profiles. The drug release mechanisms obtained can also be related to the porous structure. Fickian diffusion was the main mechanism involved in drug release from chitosan, whereas an important contribution of erosion was detected for carboxymethylchitosan systems, probably due to its high solubility