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.
Original language | English |
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Article number | 369 |
Number of pages | 16 |
Journal | Pharmaceutics |
Volume | 11 |
Issue number | 8 |
DOIs | |
Publication status | Published - 1 Aug 2019 |
Keywords
- Orodispersible films (ODFs), fast-dissolving films, micelles, amphotericin B, fungal infections
- fast-dissolving films
- micelles
- amphotericin B
- fungal infections