Mucoadhesive wafers loaded with econazole-cyclodextrin complexes for treatment of oral candidiasis

Candidosis is one of the most common fungal infections of the oral cavity in humans, caused by yeasts of the genus Candida. Its clinical aspects run from relatively trivial conditions, such as oral thrush, up to systemic super-infections in immuno-compromised patients, with mortality of 30-50%. Despite the availability of several effective antimycotics for the treatment of oral candidosis, failure of the therapy is not uncommon, due to the unique properties of the oral cavity, where both the saliva flushing and the oral musculature cleansing action tend to reduce the local drug concentration to sub-therapeutic levels. Therefore, the aim of this work was to develop a lyophilized wafer formulation based on mixtures of low methylester amidated pectin (LMAP) and carboxymethylcellulose (CMC), which applied to the oral mucosal surface, should allow a prolonged residence time and a controlled release of econazole nitrate (ECN). To overcome the problems of low ECN solubility, the drug was loaded as a ternary complex with sulphobutyl-β-cyclodextrin (SBEβCD) and citric acid (CA). Combination of LMAP and CMC, in suitable proportions, allowed preparation of lyophilized wafers able to form mucoadhesive hydrogels on contact with saliva and to ensure a prolonged residence time and controlled release of the drug.