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Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis
Amphotericin B possesses high activity against Candida spp. with low risk of resistance. However, Amphotericin B’s high molecular weight compared to other antifungal drugs, such as miconazole and clotrimazole, and poor water solubility hampers its efficacy at the physiological conditions of the orop...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723921/ https://www.ncbi.nlm.nih.gov/pubmed/31374879 http://dx.doi.org/10.3390/pharmaceutics11080369 |
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author | Serrano, Dolores R. Fernandez-Garcia, Raquel Mele, Marta Healy, Anne Marie Lalatsa, Aikaterini |
author_facet | Serrano, Dolores R. Fernandez-Garcia, Raquel Mele, Marta Healy, Anne Marie Lalatsa, Aikaterini |
author_sort | Serrano, Dolores R. |
collection | PubMed |
description | Amphotericin B possesses high activity against Candida spp. with low risk of resistance. However, Amphotericin B’s high molecular weight compared to other antifungal drugs, such as miconazole and clotrimazole, and poor water solubility hampers its efficacy at the physiological conditions of the oropharyngeal cavity (saliva pH, limited volume for dissolution) and thereby limits its clinical use in oropharyngeal candidiasis. We have prepared fast-dissolving orodispersible films with high loading (1% w/w) using solvent casting that enables amphotericin B to remain solubilised in saliva in equilibrium between the monomeric and dimeric states, and able to produce a local antifungal effect. Optimisation of the amphotericin B-loaded orodispersible films was achieved by quality by design studies combining dextran and/or maltodextrin as dextrose-derived-polymer film formers with cellulose-derived film formers (hydroxypropylmethyl/hydroxypropyl cellulose in a 1:4 weight ratio), sorbitol for taste masking, microcrystalline cellulose (Avicel 200) or microcrystalline cellulose-carboxymethylcellulose sodium (Avicel CL-611) for enhancing the mechanical strength of the film, and polyethylene glycol 400 and glycerol (1:1 w/w) as plasticizers. The optimised amphotericin B orodispersible films (containing 1% AmB, 25% dextran, 25% maltodextrin, 5% sorbitol, 10% Avicel 200, 10% polyethylene glycol 400, 10% glycerol, 3% hydroxypropylmethyl cellulose acetate succinate, 12% hydroxypropyl cellulose) possessed a fast disintegration time (60 ± 3 s), quick release in artificial saliva (>80% in 10 min), high burst strength (2190 mN mm) and high efficacy against several Candida spp. (C. albicans, C. parapsilosis and C. krusei) (>15 mm inhibition halo). Amphotericin B orodispersible films are stable for two weeks at room temperature (25 °C) and up to 1 year in the fridge. Although further toxicological and in vivo efficacy studies are required, this novel Amphotericin B orodispersible films is a promising, physicochemically stable formulation with potential wide application in clinical practice, especially for immunocompromised patients suffering from oropharyngeal candidiasis. |
format | Online Article Text |
id | pubmed-6723921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67239212019-09-10 Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis Serrano, Dolores R. Fernandez-Garcia, Raquel Mele, Marta Healy, Anne Marie Lalatsa, Aikaterini Pharmaceutics Article Amphotericin B possesses high activity against Candida spp. with low risk of resistance. However, Amphotericin B’s high molecular weight compared to other antifungal drugs, such as miconazole and clotrimazole, and poor water solubility hampers its efficacy at the physiological conditions of the oropharyngeal cavity (saliva pH, limited volume for dissolution) and thereby limits its clinical use in oropharyngeal candidiasis. We have prepared fast-dissolving orodispersible films with high loading (1% w/w) using solvent casting that enables amphotericin B to remain solubilised in saliva in equilibrium between the monomeric and dimeric states, and able to produce a local antifungal effect. Optimisation of the amphotericin B-loaded orodispersible films was achieved by quality by design studies combining dextran and/or maltodextrin as dextrose-derived-polymer film formers with cellulose-derived film formers (hydroxypropylmethyl/hydroxypropyl cellulose in a 1:4 weight ratio), sorbitol for taste masking, microcrystalline cellulose (Avicel 200) or microcrystalline cellulose-carboxymethylcellulose sodium (Avicel CL-611) for enhancing the mechanical strength of the film, and polyethylene glycol 400 and glycerol (1:1 w/w) as plasticizers. The optimised amphotericin B orodispersible films (containing 1% AmB, 25% dextran, 25% maltodextrin, 5% sorbitol, 10% Avicel 200, 10% polyethylene glycol 400, 10% glycerol, 3% hydroxypropylmethyl cellulose acetate succinate, 12% hydroxypropyl cellulose) possessed a fast disintegration time (60 ± 3 s), quick release in artificial saliva (>80% in 10 min), high burst strength (2190 mN mm) and high efficacy against several Candida spp. (C. albicans, C. parapsilosis and C. krusei) (>15 mm inhibition halo). Amphotericin B orodispersible films are stable for two weeks at room temperature (25 °C) and up to 1 year in the fridge. Although further toxicological and in vivo efficacy studies are required, this novel Amphotericin B orodispersible films is a promising, physicochemically stable formulation with potential wide application in clinical practice, especially for immunocompromised patients suffering from oropharyngeal candidiasis. MDPI 2019-08-01 /pmc/articles/PMC6723921/ /pubmed/31374879 http://dx.doi.org/10.3390/pharmaceutics11080369 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Serrano, Dolores R. Fernandez-Garcia, Raquel Mele, Marta Healy, Anne Marie Lalatsa, Aikaterini Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis |
title | Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis |
title_full | Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis |
title_fullStr | Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis |
title_full_unstemmed | Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis |
title_short | Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis |
title_sort | designing fast-dissolving orodispersible films of amphotericin b for oropharyngeal candidiasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723921/ https://www.ncbi.nlm.nih.gov/pubmed/31374879 http://dx.doi.org/10.3390/pharmaceutics11080369 |
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