Development of denture-fitting, palate-mucoadhesive miconazole nitrate films for denture stomatitis

Abstract

Denture stomatitis commonly affects denture users. Most available antifungal buccal formulations cannot maintain adequate drug levels in the mouth cavity for a sufficient time unless applied frequently. In the present study, denture-fitting, palate-mucoadhesive buccal miconazole nitrate films were developed and assessed for the management of upper denture stomatitis, caused by Candida albicans, in comparison to a commercial oral gel. Three films were prepared by solvent casting; the common film ingredients apart from miconazole nitrate, included propylene glycol as plasticizer, and hydroxypropyl methylcellulose polymer as mucoadhesive film-forming agent (F1–F3). The second and third film (F2 & F3) also contained sodium carboxy methyl cellulose as an additional mucoadhesive polymer. In films F1 and F2, miconazole nitrate was dissolved in the plasticizer propylene glycol. The third film (F3) contained miconazole nitrate-loaded chitosan nanoparticles dispersed in the film matrix. Films were characterized. Performance-related tests assessed in vitro drug release, in vitro mucoadhesion, in-vitro antifungal efficiency and in vivo clinical efficacy in denture stomatitis patients (colony counts following palate swabs and pain scoring during treatment). Attachment of film to denture was also investigated in vitro. Film F3 proved statistically more effective compared to films F1 & F2 and to the commercial oral gel, based on patients’ pain scoring at three days (P ≤ 0.05) and colony count at ten days (P ≤ 0.05) post treatment initiation, in spite of reduced amount of miconazole applied per day in case of films compared to gel. Differences in fungi inhibition zones, tested under equivalent amount of miconazole per agar well, were also statistically significant (P ≤ 0.05). Film (F3) can be promoted for effective local treatment of denture-related candidiasis with reduced application frequency, and less daily amount of applied miconazole compared to a commercial oral gel application.