Publication: Desarrollo galénico de nuevas formulaciones orales de voriconazol
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2021-06-14
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Universidad Complutense de Madrid
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Abstract
La aspergilosis invasora (AI) es una micosis sistémica producida por hongos del género Aspergillus, siendo la especie patógena más común A. fumigatus. Por lo general los conidios alcanzan el organismo por inhalación y la enfermedad afecta en primer lugar a los pulmones. La AI se produce cuando la infección se disemina, lo que ocurre principalmente en individuos inmunocomprometidos, y está asociada con una elevada mortalidad. El tratamiento de elección de la AI es el voriconazol, sin embargo, su eficacia se ve limitada por su baja solubilidad en agua. Otro problema de este fármaco es su elevada hepatotoxicidad, que puede provocar la suspensión del tratamiento. Las limitaciones mencionadas se pueden resolver mediante la fabricación de dispersiones sólidas y sistemas micelares. Estas formulaciones tienen la propiedad de formar micelas en presencia de un medio acuoso, lo que proporciona ventajas como el aumento de la solubilidad, el incremento de la biodisponibilidad, la modificación en la biodistribución y la atenuación de la toxicidad...
Invasive aspergillosis (IA) is a systemic fungal infection caused by fungi of the genus Aspergillus, being A. fumigatus the most common pathogenic species. Conidia usually reach the body by inhalation, and the disease first affects the lungs. IA takes place when haematological dissemination occurs, which mainly happens in immunocompromised individuals, and it is associated with high mortality. Voriconazole is currently the first-line treatment for IA, however its effectiveness is limited by its low solubility in water. Another problem with this drug is its elevated hepatotoxicity, which can cause treatment discontinuation. These limitations can be overcome by manufacturing solid dispersions and micellar systems. These formulations have the property of forming micelles in the presence of an aqueous medim, which provides advantages such as increased solubility, risen bioavailability, modification in biodistribution and attenuation of toxicity...
Invasive aspergillosis (IA) is a systemic fungal infection caused by fungi of the genus Aspergillus, being A. fumigatus the most common pathogenic species. Conidia usually reach the body by inhalation, and the disease first affects the lungs. IA takes place when haematological dissemination occurs, which mainly happens in immunocompromised individuals, and it is associated with high mortality. Voriconazole is currently the first-line treatment for IA, however its effectiveness is limited by its low solubility in water. Another problem with this drug is its elevated hepatotoxicity, which can cause treatment discontinuation. These limitations can be overcome by manufacturing solid dispersions and micellar systems. These formulations have the property of forming micelles in the presence of an aqueous medim, which provides advantages such as increased solubility, risen bioavailability, modification in biodistribution and attenuation of toxicity...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 22-10-2020