Publicado

2025-04-08

Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study

Formulaciones autoemulsionantes sólidas conteniendo Anfotericina B: Un estudio de preformulación

Formulações sólidas autoemulsionantes contendo anfotericina B: um estudo de pré-formulação

DOI:

https://doi.org/10.15446/rcciquifa.v54n1.119557

Palabras clave:

Leishmaniasis, Fungal infections, Solubility, Solid SEDDS, Biorelevant media (en)
Leishmaniasis, Infecciones fúngicas, Solubilidad, SEDDS sólidos, Medios biorelevantes (es)
Leishmaniose, Infecções fúngicas, Solubilidade, SEDDS sólidos, Meios biorelevantes (pt)

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Autores/as

  • Francisco Alexandrino-Jr Laboratório de Micro e Nanotecnologia (LMN), VPPIS, Fundação de Oswaldo Cruz (Fiocruz), 21040361, Rio de Janeiro, RJ, Brazil
  • Michelle A. Sarcinelli Laboratório de Micro e Nanotecnologia (LMN), VPPIS, Fundação de Oswaldo Cruz (Fiocruz), 21040361, Rio de Janeiro, RJ, Brazil
  • Gabriel Barcellos Laboratório de Micro e Nanotecnologia (LMN), VPPIS, Fundação de Oswaldo Cruz (Fiocruz), 21040361, Rio de Janeiro, RJ, Brazil
  • Leny A. H. Nascimento Laboratório de Micro e Nanotecnologia (LMN), VPPIS, Fundação de Oswaldo Cruz (Fiocruz), 21040361, Rio de Janeiro, RJ, Brazil
  • Thalita M. Silva Laboratório de Micro e Nanotecnologia (LMN), VPPIS, Fundação de Oswaldo Cruz (Fiocruz), 21040361, Rio de Janeiro, RJ, Brazil
  • Kattya G. H. Silva Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), 21941902, Rio de Janeiro, RJ, Brazil
  • Livia D. Prado Laboratório de Micro e Nanotecnologia (LMN), VPPIS, Fundação de Oswaldo Cruz (Fiocruz), 21040361, Rio de Janeiro, RJ, Brazil
  • Helvécio V. A. Rocha Laboratório de Micro e Nanotecnologia (LMN), VPPIS, Fundação de Oswaldo Cruz (Fiocruz), 21040361, Rio de Janeiro, RJ, Brazil
  • Beatriz F. C. Patricio Instituto Biomédico, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), 20211005, Rio de Janeiro, RJ, Brazil.

Introduction: Amphotericin B (AmB) is a macrolide derived from Streptomyces nodosus used to treat fungal infections and leishmaniasis. Its main clinical limitation is associated with severe nephrotoxicity after iv administration. Aim: Therefore, this study aimed to develop and characterize AmB-loaded solid self-emulsifying drug delivery systems (SEDDS) for oral administration. Methodology: to reach this goal, first an extensive solubility test was performed on 45 excipients, followed by a pseudo-ternary phase diagram to understand the phase behavior after mixing the chosen excipients with intestinal biorelevant media. Thereafter, solid SEDDS were produced either by filling hard capsules with SEDDS (LFC) or by adsorbing them onto solid excipients to formulate tablets and granules. Results: Phosal 50 PG presented the highest AmB solubility, and based on the phase behavior, two formulations with different oil-surfactant proportions were selected. The nitrogen adsorption method indicated that solid excipients incorporated the SEDDS, and no significant difference between these two formulations was found regarding droplet size, PDI, and AmB concentration. Conclusions: the LFC revealed to be the most promising dosage form, not only carrying the highest drug load, but also displaying an average size assigned as the ideal range for intestinal absorption. Therefore, supporting further in vivo studies to evaluate its therapeutic potential. 

Introducción: La Anfotericina B (AmB) es un macrólido derivado de Streptomyces nodosus utilizado para tratar infecciones fúngicas y leishmaniasis. Su principal limitación clínica está asociada con una nefrotoxicidad severa después de la administración intravenosa. Objetivo: Por lo tanto, este estudio tuvo como objetivo desarrollar y caracterizar sistemas de administración de medicamentos autoemulsionantes sólidos (SEDDS) cargados con AmB para administración oral. Metodología: Para alcanzar este objetivo, primero se realizó una prueba de solubilidad extensa en 45 excipientes, seguida de un diagrama de fase pseudo-ternaria para entender el comportamiento de fase después de mezclar los excipientes elegidos con medios biorelevantes intestinales. Posteriormente, los SEDDS sólidos fueran desarrojados sea llenando cápsulas duras con SEDDS (LFC) o incorporandolos en excipientes sólidos para formular comprimidos y gránulos. Resultados: Phosal 50 PG presentó la mayor solubilidad de AmB y, basado en el comportamiento de fase, se seleccionaron dos formulaciones con diferentes proporciones de aceite y surfactante. El método de adsorción de nitrógeno indicó que los excipientes sólidos incorporaron los SEDDS, y no se encontró una diferencia significativa entre estas dos formulaciones en cuanto al tamaño de las gotas, PDI y concentración de AmB. Conclusiones: El LFC demostró ser la forma farmacéutica prometedora, no solo llevando la mayor carga de medicamento, sino también mostrando un tamaño promedio como el rango ideal para la absorción intestinal. Por lo tanto, corroborando la realización de estudios in vivo para evaluar su potencial terapéutico. 

Introdução: A Anfotericina B (AmB) é um macrolídeo, derivado de Streptomyces nodosus, usado para tratar infecções fúngicas e leishmaniose. Sua principal limitação clínica está associada à nefrotoxicidade severa após a administração intravenosa. Objetivo: Portanto, este estudo teve como objetivo desenvolver e caracterizar sistemas autoemulsionantes sólidos (SEDDS) contendo AmB para administração oral. Metodologia: Primeiramente foi realizado um extenso teste de solubilidade em 45 excipientes, seguido por um diagrama de fase pseudo-ternário para entender o comportamento de fase após a mistura dos excipientes escolhidos com meios biorelevantes intestinais. Posteriormente, os SEDDS sólidos foram produzidos preenchendo cápsulas duras com SEDDS (CL) ou adsorvendo-os em excipientes sólidos para formular comprimidos e grânulos. Resultados: a maior solubilidade da AmB foi encontrada no Phosal 50 PG. Com base no comportamento de fase, duas formulações com diferentes proporções de óleo-surfactante foram selecionadas. O método de adsorção de nitrogênio indicou que os excipientes sólidos incorporaram os SEDDS, e não foi encontrada diferença significativa entre essas duas formulações em relação ao tamanho das gotículas, PDI e concentração de AmB. Conclusões: as CL revelaram ser a forma farmacêutica mais promissora, não apenas carregando a maior carga de medicamento, mas também exibindo um tamanho médio considerado como a faixa ideal para a absorção intestinal. Portanto, corroborando com a realização de estudos in vivo para avaliar seu potencial terapêutico. 

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Cómo citar

APA

Alexandrino-Jr, F., Sarcinelli, M. A., Barcellos, G., Nascimento, L. A. H., Silva, T. M., Silva, K. G. H., Prado, L. D., Rocha, H. V. A. y Patricio, B. F. C. (2025). Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study. Revista Colombiana de Ciencias Químico-Farmacéuticas, 54(1), 231–247. https://doi.org/10.15446/rcciquifa.v54n1.119557

ACM

[1]
Alexandrino-Jr, F., Sarcinelli, M.A., Barcellos, G., Nascimento, L.A.H., Silva, T.M., Silva, K.G.H., Prado, L.D., Rocha, H.V.A. y Patricio, B.F.C. 2025. Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study. Revista Colombiana de Ciencias Químico-Farmacéuticas. 54, 1 (abr. 2025), 231–247. DOI:https://doi.org/10.15446/rcciquifa.v54n1.119557.

ACS

(1)
Alexandrino-Jr, F.; Sarcinelli, M. A.; Barcellos, G.; Nascimento, L. A. H.; Silva, T. M.; Silva, K. G. H.; Prado, L. D.; Rocha, H. V. A.; Patricio, B. F. C. Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study. Rev. Colomb. Cienc. Quím. Farm. 2025, 54, 231-247.

ABNT

ALEXANDRINO-JR, F.; SARCINELLI, M. A.; BARCELLOS, G.; NASCIMENTO, L. A. H.; SILVA, T. M.; SILVA, K. G. H.; PRADO, L. D.; ROCHA, H. V. A.; PATRICIO, B. F. C. Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study. Revista Colombiana de Ciencias Químico-Farmacéuticas, [S. l.], v. 54, n. 1, p. 231–247, 2025. DOI: 10.15446/rcciquifa.v54n1.119557. Disponível em: https://revistas.unal.edu.co/index.php/rccquifa/article/view/119557. Acesso em: 28 abr. 2025.

Chicago

Alexandrino-Jr, Francisco, Michelle A. Sarcinelli, Gabriel Barcellos, Leny A. H. Nascimento, Thalita M. Silva, Kattya G. H. Silva, Livia D. Prado, Helvécio V. A. Rocha, y Beatriz F. C. Patricio. 2025. «Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study». Revista Colombiana De Ciencias Químico-Farmacéuticas 54 (1):231-47. https://doi.org/10.15446/rcciquifa.v54n1.119557.

Harvard

Alexandrino-Jr, F., Sarcinelli, M. A., Barcellos, G., Nascimento, L. A. H., Silva, T. M., Silva, K. G. H., Prado, L. D., Rocha, H. V. A. y Patricio, B. F. C. (2025) «Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study», Revista Colombiana de Ciencias Químico-Farmacéuticas, 54(1), pp. 231–247. doi: 10.15446/rcciquifa.v54n1.119557.

IEEE

[1]
F. Alexandrino-Jr, «Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study», Rev. Colomb. Cienc. Quím. Farm., vol. 54, n.º 1, pp. 231–247, abr. 2025.

MLA

Alexandrino-Jr, F., M. A. Sarcinelli, G. Barcellos, L. A. H. Nascimento, T. M. Silva, K. G. H. Silva, L. D. Prado, H. V. A. Rocha, y B. F. C. Patricio. «Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study». Revista Colombiana de Ciencias Químico-Farmacéuticas, vol. 54, n.º 1, abril de 2025, pp. 231-47, doi:10.15446/rcciquifa.v54n1.119557.

Turabian

Alexandrino-Jr, Francisco, Michelle A. Sarcinelli, Gabriel Barcellos, Leny A. H. Nascimento, Thalita M. Silva, Kattya G. H. Silva, Livia D. Prado, Helvécio V. A. Rocha, y Beatriz F. C. Patricio. «Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study». Revista Colombiana de Ciencias Químico-Farmacéuticas 54, no. 1 (abril 8, 2025): 231–247. Accedido abril 28, 2025. https://revistas.unal.edu.co/index.php/rccquifa/article/view/119557.

Vancouver

1.
Alexandrino-Jr F, Sarcinelli MA, Barcellos G, Nascimento LAH, Silva TM, Silva KGH, Prado LD, Rocha HVA, Patricio BFC. Solid self-emulsifying dosage forms for carrying Amphotericin B: A preformulation study. Rev. Colomb. Cienc. Quím. Farm. [Internet]. 8 de abril de 2025 [citado 28 de abril de 2025];54(1):231-47. Disponible en: https://revistas.unal.edu.co/index.php/rccquifa/article/view/119557

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