RT Journal Article
T1 Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis
A1 Serrano López, Dolores Remedios
A1 Fernández García, Raquel
A1 Mele, Marta
A1 Healy, Anne Marie
A1 Lalatsa, Aikaterini
AB 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 e_cacy 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 e_ect. 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 e_cacy against several Candida spp. (C. albicans, C. parapsilosis and C. krusei) (>15mminhibition 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 e_cacy 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 su_ering from oropharyngeal candidiasis.
PB MDPI
SN 1999-4923
YR 2019
FD 2019-08-01
LK https://hdl.handle.net/20.500.14352/12752
UL https://hdl.handle.net/20.500.14352/12752
LA eng
NO Science Foundation Ireland/FEDER
NO University of Portsmouth, Research and Development Fund
DS Docta Complutense
RD 6 abr 2025