Publication: Desarrollo farmacéutico de formulaciones pulmonares y orales de anfotericina con acción antifúngica y antiparasitaria
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2023-05-09
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Universidad Complutense de Madrid
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Abstract
La anfotericina B (AmB) es un fármaco caracterizado por presentar un amplio espectro antifúngico y antiparasitario. Se administra por vía parenteral debido a su escasa absorción oral. A pesar de su eficacia, su uso clínico se ve limitado por la aparición de eventos adversos, principalmente nefrotoxicidad y hemólisis. La Fungizona® fue el primer medicamento comercializado, pero, en la mayoría de los países, ha sido desplazada por formulaciones lipídicas de AmB (Abelcet® Amphocil® y Ambisome®) que presentan un balance beneficio/riesgo más favorable, sin embargo, tienen un coste muy elevado y requieren de condiciones ambulatorias/ hospitalarias para administrarlos al paciente. Por este motivo, existe una necesidad clínica de desarrollar formulaciones de AmB que presenten una buena relación coste-eficacia y que sean seguras para tratar infecciones fúngicas y parasitarias. Con este objetivo se desarrollaron nuevas formulaciones orales de AmB combinando diferentes excipientes mediante el recubrimiento de pellets con formulaciones líquidas micelares de AmB. Con estas nuevas formulaciones se consigue mejorar el índice terapéutico en comparación con la AmB convencional, mejorando la actividad in vitro frente a candida y disminuyendo su toxicidad hemolítica, lo que se debe, principalmente a los excipientes utilizados en la formulación líquida que recubre los pellets, así como de la proporción de los mismos...
Amphotericin B (AmB) is a broad antifungal and antiparasitic drug, usually administered by intravenous infusion due to its low aqueous solubility and low oral absorption. AmB clinical use is limited by its acute toxicity presenting, mainlys fever and gastrointestinal symptoms as well as chronic toxicity related to haemolysis and nephrotoxicity. Fungizone’s low therapeutic index is responsible for its replacement by novel lipid AmB formulations (Abelcet®, Amphocil® y Ambisome®) with more favourable risk-benefit ratio, but witha very high cost, which limits their use in developing countries. Thus, there is an increased need to engineer cost-effective and safe AmB formulations for the treatment of fungal and parasitic diseases.Novel oral AmB formulations were developed combining different excipients by spray coated beads with AmB micellar formulations. These new formulations improve the therapeutic index compared to conventional AmB as well as thein vitro activity against candida. The AmB pellets formulations showed a reduction in AmB haemolytic toxicity. These advantages are mainly due to the excipients used in the liquid formulation to the coated layer and the ratio between beads and coating excipients...
Amphotericin B (AmB) is a broad antifungal and antiparasitic drug, usually administered by intravenous infusion due to its low aqueous solubility and low oral absorption. AmB clinical use is limited by its acute toxicity presenting, mainlys fever and gastrointestinal symptoms as well as chronic toxicity related to haemolysis and nephrotoxicity. Fungizone’s low therapeutic index is responsible for its replacement by novel lipid AmB formulations (Abelcet®, Amphocil® y Ambisome®) with more favourable risk-benefit ratio, but witha very high cost, which limits their use in developing countries. Thus, there is an increased need to engineer cost-effective and safe AmB formulations for the treatment of fungal and parasitic diseases.Novel oral AmB formulations were developed combining different excipients by spray coated beads with AmB micellar formulations. These new formulations improve the therapeutic index compared to conventional AmB as well as thein vitro activity against candida. The AmB pellets formulations showed a reduction in AmB haemolytic toxicity. These advantages are mainly due to the excipients used in the liquid formulation to the coated layer and the ratio between beads and coating excipients...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 16-09-2022