Optimization of local delivery of antifungal agents in the oral cavity by a new formulation

Abstract

In recent years, with the increased use of antibiotics and immunosuppres-sive agents, there was an increased incidence of oral mycosis and Candida albicans is the most common etiologic agent in oropharyngeal candidiasis, especially in patients with HIV. The aim of this work is to develop a new dosage form containing miconazole (MN) to be topically applied on oral mucosa, allowing for a massive penetration of the drug in the tissue. The vehicle for the drug delivery was lipid microparticles incorporated in a hydrophilic gel. The lipospheres were obtained by hot melt encapsulation method using as matrix ingredients a mixtures of esters of fatty acids with higher fatty alcohols, having low melting point and a composition similar to that of some lipid membrane components The microparticles were characterized for particle size (by laser light scattering), entrapment efficiency (by UV-Vis analysis) morphology (optical microscopy) and physical state (DSC) The hydrophilic gel contained also lemon essence to enhance the palatability of product and increase the compliance of patient. The oral tissue penetration of MN released from the lipospheres alone or incorporated in gel was evaluated ex-vivo using franz diffusion cell and buccal porcine mucosa. The results were compared with behaviour of commercial Daktarin® oral gel. The lipid microparticles increase significantly the accumulative uptake of MN in buccal mucosa over the marketed gel and showed a considerably enhanced mucosa targeting effect, even at very low doses. These results indicate that the studied lipospheres/gel formulation may be a promising carrier for topical delivery of MN in the oral cavity.