Amphotericin B possesses high activity against Candida spp. with low risk of resistance.\nHowever, Amphotericin Bâ??s high molecular weight compared to other antifungal drugs, such as\nmiconazole and clotrimazole, and poor water solubility hampers its efficacy at the physiological\nconditions of the oropharyngeal cavity (saliva pH, limited volume for dissolution) and thereby limits\nits clinical use in oropharyngeal candidiasis. We have prepared fast-dissolving orodispersible films\nwith high loading (1% w/w) using solvent casting that enables amphotericin B to remain solubilised\nin saliva in equilibrium between the monomeric and dimeric states, and able to produce a local\nantifungal effect. Optimisation of the amphotericin B-loaded orodispersible films was achieved by\nquality by design studies combining dextran and/or maltodextrin as dextrose-derived-polymer film\nformers with cellulose-derived film formers (hydroxypropylmethyl/hydroxypropyl cellulose in a 1:4\nweight ratio), sorbitol for taste masking, microcrystalline cellulose (Avicel 200) or microcrystalline\ncellulose-carboxymethylcellulose sodium (Avicel CL-611) for enhancing the mechanical strength of the\nfilm, and polyethylene glycol 400 and glycerol (1:1 w/w) as plasticizers. The optimised amphotericin B\norodispersible films (containing 1% AmB, 25% dextran, 25% maltodextrin, 5% sorbitol, 10% Avicel\n200, 10% polyethylene glycol 400, 10% glycerol, 3% hydroxypropylmethyl cellulose acetate succinate,\n12% hydroxypropyl cellulose) possessed a fast disintegration timeâ?¦â?¦â?¦â?¦â?¦..
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