Next Article in Journal
Pharmacokinetics of B-Ring Unsubstituted Flavones
Previous Article in Journal
Improved In Vitro Model for Intranasal Mucosal Drug Delivery: Primary Olfactory and Respiratory Epithelial Cells Compared with the Permanent Nasal Cell Line RPMI 2650
Previous Article in Special Issue
Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis
Article Menu

Export Article

Open AccessArticle

Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis

1
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramon y Cajal s/n, 28040 Madrid, Spain
2
Instituto Universitario de Farmacia Industrial (IUFI), School of Pharmacy, Universidad Complutense de Madrid, Avenida Complutense, 28040 Madrid, Spain
3
School of Pharmacy and Biomedical Sciences, University of Portsmouth, St. Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UK
4
Synthesis and Solid State Pharmaceutical Centre, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(8), 369; https://doi.org/10.3390/pharmaceutics11080369
Received: 7 June 2019 / Revised: 20 July 2019 / Accepted: 22 July 2019 / Published: 1 August 2019
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
  |  
PDF [3719 KB, uploaded 1 August 2019]
  |  

Abstract

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. View Full-Text
Keywords: orodispersible films; fast-dissolving films; micelles; amphotericin B; fungal infections orodispersible films; fast-dissolving films; micelles; amphotericin B; fungal infections
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Serrano, D.R.; Fernandez-Garcia, R.; Mele, M.; Healy, A.M.; Lalatsa, A. Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis. Pharmaceutics 2019, 11, 369.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top