Azithromycin (AZT) is one of the most prescribed antibiotics in children, generally administered through the oral route. However, its low aqueous solubility, poor oral bioavailability and bitter taste can affect the therapy efficacy and the children's compliance. In this study, different mucoadhesive polymers and solubilizers were explored to develop a primary layer capable of establishing a prolonged contact with the mucosa. An ethylcellulose layer was further applied to assure the drug unidirectional absorption through the buccal mucosa and limit its bitter taste in the mouth. Films were characterized for their thickness, drug content and solid state, morphology, hydration mucoadhesion and mechanical properties. In vitro drug release and permeation through the buccal mucosa as well as antimicrobial activity were also investigated. The selected compositions, based on chitosan (CS), alginate (ALG) or sodium hyaluronate (HYA) in association with Soluplus® or polyvinylpyrrolidones allowed to obtain uniform, thin and mucoadhesive films. CS films determined a quick AZT release, due to the presence of a new, more soluble form of the drug (confirmed by PXRD and FT-IR analysis) with unaltered antimicrobial properties. Conversely, HYA and ALG films showed a more sustained release. Interestingly, the presence of the backing layer, confirmed by morphological studies, hindered the drug release, thus demonstrating that films could limit AZT taste inside the mouth. Among all the formulations, HYA film was characterized by the best profile of drug permeation, allowing the retention of drug antimicrobial ability and can be proposed as a buccal delivery system for the systemic absorption of AZT.
Keywords: Azithromycin; Bilayered buccal films; Children; Permeation studies; Transmucosal administration.
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